Search

Recent randomized controlled trials (RCTs) have shown no benefit but  dose-dependent harm by early full nutritional support in critically ill patients. Lack of benefit may be explained by anabolic resistance, suppression of cellular repair processes, and aggravation of hyperglycemia and insulin needs. Also early high amino acid doses did not provide benefit, but instead associated with harm in patients with organ dysfunctions. However, most studies focused on nutritional interventions initiated during the first days after intensive care unit admission. Although the intervention window of some RCTs extended into the post-acute phase of critical illness, no large RCTs studied nutritional interventions initiated beyond the first week. Hence, clear evidence-based guidance on when and how to initiate and advance nutrition is lacking. Prolonged underfeeding will come at a price as there is no validated metabolic monitor that indicates readiness for medical nutrition therapy, and an adequate response to nutrition, which likely varies between patients. Also micronutrient status cannot be assessed reliably, as inflammation can cause redistribution, so that plasma micronutrient concentrations are not necessarily reflective of total body stores. Moreover, high doses of individual micronutrients have not proven beneficial. Accordingly, current evidence provides clear guidance on which nutritional strategies to avoid, but the ideal nutritional regimen for individual patients remains unclear. In this narrative review, we summarize the findings of recent studies, discuss possible mechanisms explaining the results, point out pitfalls in interpretation of RCTs and their effect on clinical practice, and formulate suggestions for future research., (© 2024. The Author(s).)

Purpose of Review: To summarize the incidence, features, pathogenesis, risk factors, and evidence-based therapies of prolonged intensive care unit (ICU) acquired weakness (ICU-AW). We aim to provide an updated overview on aspects of poor physical recovery following critical illness., Recent Findings: New physical problems after ICU survival, such as muscle weakness, weakened condition, and reduced exercise capacity, are the most frequently encountered limitations of patients with postintensive care syndrome. Disabilities may persist for months to years and frequently do not fully recover. Hormonal and mitochondrial disturbances, impaired muscle regeneration due to injured satellite cells and epigenetic differences may be involved in sustained ICU-AW. Although demographics and ICU treatment factors appear essential determinants for physical recovery, pre-ICU health status is also crucial. Currently, no effective treatments are available. Early mobilization in the ICU may improve physical outcomes at ICU-discharge, but there is no evidence for benefit on long-term physical recovery., Summary: Impaired physical recovery is observed frequently among ICU survivors. The pre-ICU health status, demographic, and ICU treatment factors appear to be important determinants for physical convalescence during the post-ICU phase. The pathophysiological mechanisms involved are poorly understood, thereby resulting in exiguous evidence-based treatment strategies to date., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

This article presents 7 nutrition steps that, if not followed by the clinical staff, may be metaphorically considered as "7 deadly sins" of nutrition therapy. In this review, we suggest approaches that must be avoided or accomplished to increase compliance with the "Ten Commandments" of good nutrition practice in the intensive care setting. Multiple aggressive and simultaneous sets of therapies are implemented in the intensive care setting, which include nutrition and metabolic support as important components in these therapies. "Sins" should be remembered as a mnemonic device for nutrition standard care in the intensive care unit; this incorporates nutrition adequacy and protocol adherence., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Objectives: To examine the effect of hypocaloric/hyperproteic enteral feeding vs normocaloric feeding on the survival of critically ill patients in the acute phase in the intensive care unit (ICU). Methodology: Randomized clinical trials utilizing hypocaloric, hyperproteic, and normocaloric enteral feeding in the ICU were searched using the following terms ((((critically ill) OR (intensive care) OR (mechanically ventilated)) AND ((low-calorie enteral feeding) OR (high-protein enteral feeding)))) in MEDLINE, PubMed, Scopus, and Google Scholar by two independent authors. Results: There were no significant differences in hospital mortality [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.77, 1.31; p = 0.99, I² = 0%], days on mechanical ventilation (MD, -0.05; 95% CI, -0.37, 0.28; p = 0.78, I² = 0%), the odds of acquiring infectious complications (OR, 0.90; 95% CI, 0.71, 1.14; p = 0.38, I² = 0%), and the length of ICU stay (MD, 0.60; 95% CI, -2.39, 3.59; p = 0.69, I² = 96%). The length of hospital stay was significantly lower by 4.18 days in the normocaloric group (MD, 4.18; 95% CI, 2.50, 5.85; p < 0.00001, I² = 0%). Conclusion: This meta-analysis showed no significant differences in mortality, infectious complications, days of mechanical ventilation, and ICU length of stay between groups. Findings on hospital length of stay were interpreted with caution due to the low quality of evidence and clinical heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Although the optimization of brain oxygenation is thought to improve the prognosis, the effect of brain tissue oxygen pressure (PbtO2) for patients with severe traumatic brain injury (STBI) remains controversial. Therefore, the present study aimed to determine whether adding PbtO2 to intracranial pressure (ICP) monitoring improves clinical outcomes for patients with STBI. Methods: PubMed, Embase, Scopus and Cochrane Library were searched for eligible trials from their respective inception through April 10th, 2024. We included clinical trials contrasting the combined monitoring of PbtO2 and ICP versus isolated ICP monitoring among patients with STBI. The primary outcome was favorable neurological outcome at 6 months, and secondary outcomes including the in-hospital mortality, long-term mortality, length of stay in intensive care unit (ICU) and hospital. Results: A total of 16 studies (four randomized studies and 12 cohort studies) were included in the meta-analysis. Compared with isolated ICP monitoring, the combined monitoring was associated with a higher favorable neurological outcome rate at 6 months (RR 1.33, 95% CI [1.17–1.51], P < 0.0001, I2 = 0%), reduced long-term mortality (RR 0.72, 95% CI [0.59–0.87], P = 0.0008, I2 = 2%). No significant difference was identified in the in-hospital mortality (RR 0.81, 95% CI 0.66 to 1.01, P = 0.06, I2 = 32%), length of stay in ICU (MD 2.10, 95% CI [−0.37–4.56], P = 0.10, I2 = 78%) and hospital (MD 1.07, 95% CI [−2.54–4.67], P = 0.56, I2 = 49%) between two groups. However, the pooled results of randomized studies did not show beneficial effect of combined monitoring in favorable neurological outcome and long-term mortality. Conclusions: Currently, there is limited evidence to prove that the combined PbtO2 and ICP monitoring may contribute to improved neurological outcome and long-term mortality for patients with STBI. However, the benefit of combined monitoring should be further validated in more randomized studies. [ABSTRACT FROM AUTHOR]

Post-intensive care syndrome (PICS) is a triad of physical, cognitive, and mental impairments that occur during or following the intensive care unit (ICU) stay, affecting the long-term prognosis of the patient and also the mental health of the patient's family. While the severity and duration of the systemic inflammation are associated with the occurrence of ICU-acquired weakness (ICU-AW), malnutrition and immobility during the treatment can exacerbate the symptoms. The goal of nutrition therapy in critically ill patients is to provide an adequate amount of energy and protein while addressing specific nutrient deficiencies to survive the inflammatory response and promote recovery from organ dysfunctions. Feeding strategy to prevent ICU-AW and PICS as nutrition therapy involves administering sufficient amounts of amino acids or proteins later in the acute phase after the hyperacute phase has passed, with specific attention to avoid energy overfeeding. Physiotherapy can also help mitigate muscle loss and subsequent physical impairment. However, many questions remain to be answered regarding the potential role and methods of nutrition therapy in association with ICU-AW and PICS, and further research is warranted. [ABSTRACT FROM AUTHOR]

Background: Sepsis-associated acute kidney injury (AKI) is a leading comorbidity in admissions to the intensive care unit. While a gold standard definition exists, it remains imperfect and does not allow for the timely identification of patients in the setting of critical illness. This review will discuss the use of biochemical and electronic biomarkers to allow for prognostic and predictive enrichment of patients with sepsis-associated AKI over and above the use of serum creatinine and urine output. Summary: Current data suggest that several biomarkers are capable of identifying patients with sepsis at risk for the development of severe AKI and other associated morbidity. This review discusses these data and these biomarkers in the setting of sub-phenotyping and endotyping sepsis-associated AKI. While not all these tests are widely available and some require further validation, in the near future we anticipate several new tools to help nephrologists and other providers better care for patients with sepsis-associated AKI. Key Messages: Predictive and prognostic enrichment using both traditional biomarkers and novel biomarkers in the setting of sepsis can identify subsets of patients with either similar outcomes or similar pathophysiology, respectively. Novel biomarkers can identify kidney injury in patients without consensus definition AKI (e.g., changes in creatinine or urine output) and can predict other adverse outcomes (e.g., severe consensus definition AKI, inpatient mortality). Finally, emerging artificial intelligence and machine learning-derived risk models are able to predict sepsis-associated AKI in critically ill patients using advanced learning techniques and several laboratory and vital sign measurements. [ABSTRACT FROM AUTHOR]

Asprosin, a new adipokine, is secreted by subcutaneous white adipose tissue and causes rapid glucose release. The skeletal muscle mass gradually diminishes with aging. The combination of decreased skeletal muscle mass and critical illness may cause poor clinical outcomes in critically ill older adults. To determine the relationship between the serum asprosin level, fat-free mass, and nutritional status of critically ill older adult patients, critically ill patients over the age of 65 receiving enteral nutrition via feeding tube were included in the study. The patients' cross-sectional area of the rectus femoris (RF) of the lower extremity quadriceps muscle was evaluated by serial measurements. The mean age of the patients was 72 ± 6 years. The median (IQR) serum asprosin level was 31.8 (27.4–38.1) ng/mL on the first study day and 26.1 (23.4–32.3) ng/mL on the fourth study day. Serum asprosin level was high in 96% of the patients on the first day, and it was high in 74% on the fourth day after initiation of enteral feeding. The patients achieved 65.9 ± 34.1% of the daily energy requirement for four study days. A significant moderate correlation between delta serum asprosin level and delta RF was found (Rho = −0.369, p = 0.013). In critically ill older adult patients, a significant negative correlation was determined between serum asprosin level with energy adequacy and lean muscle mass. [ABSTRACT FROM AUTHOR]

Background: Altered DNA-methylation affects biological ageing in adults and developmental processes in children. DNA-methylation is altered by environmental factors, trauma and illnesses. We hypothesised that paediatric critical illness, and the nutritional management in the paediatric intensive care unit (PICU), affects DNA-methylation changes that underly the developmental processes of childhood ageing. Results: We studied the impact of critical illness, and of the early use of parenteral nutrition (early-PN) versus late-PN, on "epigenetic age-deviation" in buccal mucosa of 818 former PICU-patients (406 early-PN, 412 late-PN) who participated in the 2-year follow-up of the multicentre PEPaNIC-RCT (ClinicalTrials.gov-NCT01536275), as compared with 392 matched healthy children, and assessed whether this relates to their impaired growth. The epigenetic age-deviation (difference between PedBE clock-estimated epigenetic age and chronological age) was calculated. Using bootstrapped multivariable linear regression models, we assessed the impact hereon of critical illness, and of early-PN versus late-PN. As compared with healthy children, epigenetic age of patients assessed 2 years after PICU-admission deviated negatively from chronological age (p < 0.05 in 51% of bootstrapped replicates), similarly in early-PN and late-PN groups. Next, we identified vulnerable subgroups for epigenetic age-deviation using interaction analysis. We revealed that DNA-methylation age-deceleration in former PICU-patients was dependent on age at time of illness (p < 0.05 for 83% of bootstrapped replicates), with vulnerability starting from 6 years onwards. Finally, we assessed whether vulnerability to epigenetic age-deviation could be related to impaired growth from PICU-admission to follow-up at 2 and 4 years. Multivariable repeated measures ANOVA showed that former PICU-patients, as compared with healthy children, grew less in height (p = 0.0002) and transiently gained weight (p = 0.0003) over the 4-year time course. Growth in height was more stunted in former PICU-patients aged ≥ 6-years at time of critical illness (p = 0.002) than in the younger patients. Conclusions: As compared with healthy children, former PICU-patients, in particular those aged ≥ 6-years at time of illness, revealed epigenetic age-deceleration, with a physical correlate revealing stunted growth in height. Whether this vulnerability around the age of 6 years for epigenetic age-deceleration and stunted growth years later relates to altered endocrine pathways activated at the time of adrenarche requires further investigation. [ABSTRACT FROM AUTHOR]

Clinical risk assessments should be made to protect patients from negative outcomes, and the definition, frequency and severity of the risk should be determined. The information contained in the electronic health records (EHRs) can use in different areas such as risk prediction, estimation of treatment effect ect. Many prediction models using artificial intelligence (AI) technologies that can be used in risk assessment have been developed. The aim of this study is to bring together the researches on prediction models developed with AI technologies using the EHRs of patients hospitalized in the intensive care unit (ICU) and to evaluate them in terms of risk management in healthcare. The study restricted the search to the Web of Science, Pubmed, Science Direct, and Medline databases to retrieve research articles published in English in 2010 and after. Studies with a prediction model using data obtained from EHRs in the ICU are included. The study focused solely on research conducted in ICU to predict a health condition that poses a significant risk to patient safety using artificial intellegence (AI) technologies. Recognized prediction subcategories were mortality (n=6), sepsis (n=4), pressure ulcer (n=4), acute kidney injury (n=3), and other areas (n=10). It has been found that EHR-based prediction models are good risk management and decision support tools and adoption of such models in ICUs may reduce the prevalence of adverse conditions. The article results remarks that developed models was found to have higher performance and better selectivity than previously developed risk models, so they are better at predicting risks and serious adverse events in ICU. It is recommended to use AI based prediction models developed using EHRs in risk management studies. Future work is still needed to researches to predict different health conditions risks. [ABSTRACT FROM AUTHOR]

Background: Post‐intensive care syndrome (PICS) encompasses physical, cognition, and mental impairments persisting after intensive care unit (ICU) discharge. Ultimately it significantly impacts the long‐term prognosis, both in functional outcomes and survival. Thus, survivors often develop permanent disabilities, consume a lot of healthcare resources, and may experience prolonged suffering. This review aims to present the multiple facets of the PICS, decipher its underlying mechanisms, and highlight future research directions. Main text: This review abridges the translational data underlying the multiple facets of chronic critical illness (CCI) and PICS. We focus first on ICU-acquired weakness, a syndrome characterized by impaired contractility, muscle wasting, and persisting muscle atrophy during the recovery phase, which involves anabolic resistance, impaired capacity of regeneration, mitochondrial dysfunction, and abnormalities in calcium homeostasis. Second, we discuss the clinical relevance of post-ICU cognitive impairment and neuropsychological disability, its association with delirium during the ICU stay, and the putative role of low-grade long-lasting inflammation. Third, we describe the profound and persistent qualitative and quantitative alteration of the innate and adaptive response. Fourth, we discuss the biological mechanisms of the progression from acute to chronic kidney injury, opening the field for renoprotective strategies. Fifth, we report long-lasting pulmonary consequences of ARDS and prolonged mechanical ventilation. Finally, we discuss several specificities in children, including the influence of the child's pre-ICU condition, development, and maturation. Conclusions: Recent understandings of the biological substratum of the PICS' distinct features highlight the need to rethink our patient trajectories in the long term. A better knowledge of this syndrome and precipitating factors is necessary to develop protocols and strategies to alleviate the CCI and PICS and ultimately improve patient recovery. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) causes alteration in brain functions. Generally, at intensive care units (ICU), intracranial pressure (ICP) is monitored and treated to avoid increases in ICP with associated poor clinical outcome. The aim was to develop a model which could predict future ICP levels of individual patients in the ICU, to warn treating clinicians before secondary injuries occur. A simple and explainable, probabilistic Markov model was developed for the prediction task ICP ≥ 20 mmHg. Predictions were made for 10-min intervals during 60 min, based on preceding hour of ICP. A prediction enhancement method was developed to compensate for data imbalance. The model was evaluated on 29 patients with severe TBI. With random data selection from all patients (80/20% training/testing) the specificity of the model was high (0.94–0.95) and the sensitivity good to high (0.73–0.87). Performance was similar (0.90–0.95 and 0.73–0.89 respectively) when the leave-one-out cross-validation was applied. The new model could predict increased levels of ICP in a reliable manner and the enhancement method further improved the predictions. Further advantages are the straightforward expandability of the model, enabling inclusion of other time series data and/or static parameters. Next step is evaluation on more patients and inclusion of parameters other than ICP. [ABSTRACT FROM AUTHOR]

As survival after pediatric intensive care unit (PICU) admission has improved over recent years, a key focus now is the reduction of morbidities and optimization of quality of life for survivors. Neurologic disorders and direct brain injuries are the reason for 11–16% of admissions to PICU. In addition, many critically ill children are at heightened risk of brain injury and neurodevelopmental difficulties affecting later life, e.g., complex heart disease and premature birth. Hence, assessment, monitoring and protection of the brain, using fundamental principles of neurocritical care, are crucial to the practice of pediatric intensive care medicine. The assessment of brain function, necessary to direct appropriate care, is uniquely challenging amongst children admitted to the PICU. Challenges in assessment arise in children who are unstable, or pharmacologically sedated and muscle relaxed, or who have premorbid abnormality in development. Moreover, the heterogeneity of diseases and ages in PICU patients, means that high caliber evidence is harder to accrue than in adult practice, nonetheless, great progress has been made over recent years. In this 'state of the art' paper about critically ill children, we discuss (1) patient types at risk of brain injury, (2) new standardized clinical assessment tools for age-appropriate, clinical evaluation of brain function, (3) latest evidence related to cranial imaging, non-invasive and invasive monitoring of the brain, (4) the concept of childhood 'post intensive are syndrome' and approaches for neurodevelopmental follow-up. Better understanding of these concepts is vital for taking PICU survivorship to the next level. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a leading neurological cause of death and disability across the world. Early characterization of TBI severity could provide a window for therapeutic intervention and contribute to improved outcome. We hypothesized that granular electronic health record data available in the first 24 h following admission to the intensive care unit (ICU) can be used to differentiate outcomes at discharge. Working from two ICU datasets we focused on patients with a primary admission diagnosis of TBI whose length of stay in ICU was ≥ 24 h (N = 1689 and 127). Features derived from clinical, laboratory, medication, and physiological time series data in the first 24 h after ICU admission were used to train elastic-net regularized Generalized Linear Models for the prediction of mortality and neurological function at ICU discharge. Model discrimination, determined by area under the receiver operating characteristic curve (AUC) analysis, was 0.903 and 0.874 for mortality and neurological function, respectively. Model performance was successfully validated in an external dataset (AUC 0.958 and 0.878 for mortality and neurological function, respectively). These results demonstrate that computational analysis of data routinely collected in the first 24 h after admission accurately and reliably predict discharge outcomes in ICU stratum TBI patients. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular weakness may manifest subsequent to critical illness in intensive care unit (ICU) patients. This weakness termed as "ICU-acquired weakness" (ICUAW) has a significant bearing on the length of mechanical ventilation, duration of ICU stays, long-term disability, and survival rate. Early identification of ICUAW helps in planning appropriate strategies, as well as in predicting the prognosis and long-term outcomes of these patients. Aims and objectives: To identify the incidence of new-onset neuromuscular weakness developing among patients admitted in the ICU (ICUAW) and study its clinical course and impact on the duration of ICU stay. Methods: This prospective observational study evaluated patients admitted to the ICU over a period of 1 year and 3 months (November 1, 2015, to January 31, 2017). All patients fulfilling the inclusion and exclusion criteria were evaluated with the Medical Research Council (MRC) score for muscle strength. Patients with an average score <4 were diagnosed with ICUAW. Included patients were examined on alternate days to study the clinical progression of the weakness till ICU discharge or death of the patient. The duration of ICU stay was noted. Results and conclusion: The study revealed a significant association of ICUAW with age, Acute Physiology And Chronic Health Evaluation (APACHE II) Score, duration of mechanical ventilation, and ICU mortality. The incidence of the weakness was found to be 7.83% among the patients who survived and 50% among those patients who did not survive critical illness. [ABSTRACT FROM AUTHOR]

Background: Poor physical functioning (PF) is a common issue among critically ill patients. It was suggested that reasonable nutrition accelerates PF recovery. However, the details and types of nutritional interventions on the PF of different intensive care unit (ICU) patients at present have not been well analyzed yet. This study aimed to systematically synthesize nutritional interventions on PF in different ICU populations. Methods: Whittemore and Knafl's framework was employed. PubMed, EMBASE, Web of Science, CINAHL Plus with Full Text, and Cochrane Library were searched to obtain studies from January 2010 to September 2020, with a manual search of the included studies' references. Record screening, data extraction, and quality appraisal were conducted independently by each reviewer before reaching an agreement after discussion. Results: Twelve studies were included reporting the effects of early parenteral nutrition, early enteral nutrition, early goal-directed nutrition, early adequate nutrition, higher protein delivery, higher energy delivery, low energy delivery, energy and protein delivery, intermittent enteral feeding on PF like muscle mass, muscle strength, and function. Function was the most common outcome but showed little improvements. Muscle strength outcomes improved the most. The mechanically ventilated were the most popular target ICU population. The commenced time of the interventions is usually within 24 to 48 hours after ICU admission. Conclusion: Research on nutritional interventions on critically ill patients' PF is limited, but most are of a high level of evidence. Few intervention studies specified their evidence basis. Qualitative studies investigating timeframe of initiating feeding, perspectives of the patients' perspectives and caregivers are warranted to advance research and further discuss this topic. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Pediatric intensive care unit (PICU) survivors are at risk for prolonged morbidities interfering with daily life. The current study examined parent-reported health-related quality of life (HRQoL) in former critically ill children and parents themselves and aimed to determine whether withholding parenteral nutrition (PN) in the first week of critical illness affected children's and parents' HRQoL 2 years later.Methods: Children who participated in the pediatric early versus late parenteral nutrition in critical illness (PEPaNIC) trial and who were testable 2 years later (n = 1158) were included. Their HRQoL outcomes were compared with 405 matched healthy controls. At PICU admission, children had been randomly assigned to early-PN or late-PN. In the early-PN group, PN was initiated within 24 h after PICU admission. In the late-PN group, PN was withheld for up to 1 week in the PICU. Parents completed the Infant Toddler Quality of Life Questionnaire (ITQOL; age 2-3 years) or the Child Health Questionnaire-Parent Form 50 (CHQ-PF50; age 4-18 years). Besides, they completed the Health Utility Index (HUI) and the Short Form Health Survey (SF-12) regarding their child's and their own HRQoL, respectively.Results: For the total age group of 786 post-PICU survivors, parents reported lower scores for almost all HRQoL scales compared to healthy children. Age-specifically, younger critically ill children (2.5 to 3 years old) scored worse for growth and development and older children (4-18 years old) scored worse for role functioning and mental health. Parents' own mental and physical HRQoL was comparable to that of healthy control parents. No HRQoL differences were found between children in the late-PN and those in the early-PN group.Conclusions: Parent-reported HRQoL of children 2 years after critical illness was impaired compared with healthy controls. In relation to their child's HRQoL, parents reported impairments in emotions, personal time, and family activities; however, their own HRQoL was not impaired. Withholding PN in the first week during critical illness had no impact on longer-term HRQoL of the child.Trial Registration: Clinical trials, NCT01536275. Registered 22 February 2012. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend that protein be administered enterally to critically ill patients at doses between 1.2 and 2 g/kg per day Observational data indicate that patients frequently receive less protein. The aim of this systematic review was to evaluate patient-centered outcomes with guideline-recommended enteral protein compared with usual care.Methods: A systematic review was performed of randomized controlled trials including critically ill adult patients provided predominately enteral nutrition with mean protein at ≥1.2 g/kg per day (intervention) and <1.2 g/kg per day (comparator). Random-effects models were applied for outcomes reported in ≥3 trials.Results: Of 1375 abstracts, 69 full-text articles were reviewed, and 6 trials meet the inclusion criteria, including 511 patients. The intervention group received a mean (SD) of 1.3 (0.08) g/kg per day, and the comparator group received 0.75 (0.15) g/kg per day protein. Insufficient data were available for meta-analyses on the primary outcome (muscle mass or strength). According to our meta-analyses, mortality at 28 days (5 studies) (risk ratio 0.92 [95% Cl 0.63-1.35], P = .66) and the durations of intensive care unit (6 studies) and hospital admission (4 studies) were similar between the intervention and comparator, with some uncertainty due to sample sizes and heterogeneity.Conclusion: There are insufficient data to conclude whether protein provision within the current international guideline recommendations improves outcomes. In a limited dataset, enteral protein intakes near the lower level of current recommendations do not appear to reduce admission duration or mortality when compared with usual care in critically ill. [ABSTRACT FROM AUTHOR]

Purpose: Increased systemic cortisol availability during adult critical illness is determined by reduced binding-proteins and suppressed breakdown rather than elevated ACTH. Dynamics, drivers and prognostic value of hypercortisolism during pediatric critical illness remain scarcely investigated.Methods: This preplanned secondary analysis of the PEPaNIC-RCT (N = 1440), after excluding 420 children treated with corticosteroids before PICU-admission, documented (a) plasma ACTH, (free)cortisol and cortisol-metabolism at PICU-admission, day-3 and last PICU-day, their prognostic value, and impact of withholding early parenteral nutrition (PN), (b) the association between corticosteroid-treatment and these hormones, and (c) the association between corticosteroid-treatment and outcome.Results: ACTH was normal upon PICU-admission and low thereafter (p ≤ 0.0004). Total and free cortisol were only elevated upon PICU-admission (p ≤ 0.0003) and thereafter became normal despite low binding-proteins (p < 0.0001) and persistently suppressed cortisol-metabolism (p ≤ 0.03). Withholding early-PN did not affect this phenotype. On PICU-day-3, high free cortisol and low ACTH independently predicted worse outcome (p ≤ 0.003). Also, corticosteroid-treatment initiated in PICU, which further suppressed ACTH (p < 0.0001), was independently associated with poor outcomes (earlier live PICU-discharge: p < 0.0001, 90-day mortality: p = 0.02).Conclusion: In critically ill children, systemic cortisol availability is elevated only transiently, much lower than in adults, and not driven by elevated ACTH. Further ACTH lowering by corticosteroid-treatment indicates active feedback inhibition at pituitary level. Beyond PICU-admission-day, low ACTH and high cortisol, and corticosteroid-treatment, predicted poor outcome. This suggests that exogenously increasing cortisol availability during acute critical illness in children may be inappropriate. Future studies on corticosteroid-treatment in critically ill children should plan safety analyses, as harm may be possible. [ABSTRACT FROM AUTHOR]

Since a wise man or woman proportions his or her belief to the evidence [[1]], this focus on paediatrics discusses interesting and influential papers that have been published in important journals in 2018, related to paediatric intensive care unit (PICU) clinical research. The pilot trials for conservative versus liberal oxygenation targets in critically ill children (oxy-PICU) [[17]] and high flow nasal cannula oxygen versus CPAP (first ABC) [[18]], represent "for runners" to multi centre RCT starting in 2019. Overview of studies in critically ill children (search terms child, critical care OR intensive care) that are currently recruiting. 18 Ramnarayan P, Lister P, Dominguez T, Habibi P, Edmonds N, Canter RR, Wulff J, Harrison DA, Mouncey PM, Peters MJ United Kingdom Paediatric Intensive Care Society Study G. FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): a multicentre pilot randomised controlled trial of high-flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care. [Extracted from the article]

Background: International guidelines recommend greater protein delivery to critically ill patients than they currently receive. This pilot randomized clinical trial aimed to determine whether a volume-target enteral protocol with supplemental protein delivered greater amounts of protein and energy to critically ill patients compared with standard care.Methods: Sixty participants received either the intervention (volume-based protocol, with protein supplementation) or standard nutrition care (hourly-rate-based protocol, without protein supplementation) in the intensive care unit (ICU). Coprimary outcomes were average daily protein and energy delivery. Secondary outcomes included change in quadriceps muscle layer thickness (QMLT, ultrasound) and malnutrition (subjective global assessment) at ICU discharge.Results: Mean (SD) protein and energy delivery per day from nutrition therapy for the intervention were 1.2 (0.30) g/kg and 21 (5.2) kcal/kg compared with 0.75 (0.11) g/kg and 18 (2.7) kcal/kg for standard care. The mean difference between groups in protein and energy delivery per day was 0.45 g/kg (95% CI, 0.33-0.56; P < .001) and 2.8 kcal/kg (95% CI, 0.67-4.9, P = .01). Muscle loss (QMLT) at discharge was attenuated by 0.22 cm (95% CI, 0.06-0.38, P = .01) in patients receiving the intervention compared with standard care. The number of malnourished patients was fewer in the intervention [2 (7%) vs 8 (28%); P = .04]. Mortality and duration of admission were similar between groups.Conclusions: A high-protein volume-based protocol with protein supplementation delivered greater amounts of protein and energy. This intervention was associated with attenuation of QMLT loss and reduced prevalence of malnutrition at ICU discharge. [ABSTRACT FROM AUTHOR]

The article explores how big data and machine learning techniques can be utilized by high-technology intensive care units (ICUs) and ICU clinicians in their daily practice. Topics covered include development of a continuously learning healthcare system, intellectual property and patient consent issues that may arise from large-scale acquisition of medical data, and impact of machine learning on the problem of multiple testing and false positive associations.

Purpose: This study was conducted to identify changes in limb circumferences among patients admitted to the intensive care unit (ICU) and related factors. Methods: We conducted a prospective observational study with 27 patients from 3 ICUs at a university hospital located in B city of Korea, from September 1 to October 30, 2015. The circumferences of the left and right upper arms, thighs, and lower legs were measured on the first, third, fifth, and seventh days of ICU admission. Information on the related factors was collected from the medical records. The data were analyzed using a linear mixed model method. Results: The limbs circumferences significantly reduced from day 3, and the changes continued till day 7. These changes were related to the gender of the subjects, restraints application, use of steroids, and continuous renal replacement therapy. Conclusions: Based on the above results, it can be concluded that ICU-acquired weakness begins before the third day of admission. Thus, early mobilization protocols for ICU patients need to be developed and implemented in order to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Prior studies of physical functioning after critical illness have been mostly limited to survivors of acute respiratory distress syndrome. The purpose of this study was to objectively assess muscle strength and physical functioning in survivors of critical illness from a general ICU and the associations of these measures to health-related quality of life (HRQL), mental health and critical illness variables. Methods: This was a prospective cohort study of 56 patients admitted to a medical ICU (length of stay ≥4 days) from April 1, 2009, and March 31, 2010. Patients were assessed in clinic at 3 months post-hospital discharge. Muscle strength and physical functioning were measured using hand-held dynamometry and the 6-min walk test. HRQL was assessed using the short-form 36 (SF-36) and EuroQol-5D (EQ-5D) questionnaires. Results: Three months post-hospital discharge, median age- and sex-matched muscle strength was reduced across all muscle groups. The median 6-min walk distance was 72 % of predicted. Physical functioning was associated with reductions in self-reported HRQL (SF-36, EQ-5D) and increased anxiety. Univariate regression modeling showed that reduced muscle strength and 6-min walk distance were associated with sepsis but not ICU length of stay. Multivariate regression modeling showed that sepsis and corticosteroid use were associated with a reduced 6-min walk distance, but again ICU length of stay was not. Conclusions: Survivors of critical illness have reduced strength in multiple muscle groups and impaired exercise tolerance impacting both HRQL and mental health. These outcomes were worsened by sepsis and corticosteroid use in the ICU but not ICU length of stay. Interventions to minimizing the burden of sepsis in critically ill patients may improve long-term outcomes. [ABSTRACT FROM AUTHOR]

The authors talk about several research papers focusing on pathophysiology, prevention and treatment of acute kidney injury (AKI) during critical illness. Topics discussed include the risk of contrast-induced AKI in intensive care unit (ICU); the importance of accurate risk prediction or early diagnosis in prevention or treatment of AKI; and the benefits of biomarker-directed management.

Purpose: Muscle weakness in long-stay ICU patients contributes to 1-year mortality. Whether electrophysiological screening is an alternative diagnostic tool in unconscious/uncooperative patients remains unknown. We aimed to determine the diagnostic properties of abnormal compound muscle action potential (CMAP), sensory nerve action potential (SNAP), and spontaneous electrical activity (SEA) for Medical Research Council (MRC)-defined weakness and their predictive value for 1-year mortality.Methods: Data were prospectively collected during the EPaNIC trial (ClinicalTrials.gov: NCT00512122). First, sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of abnormal CMAP, SNAP, and SEA for weakness were determined. Subsequently, association between 1-year mortality and abnormal findings on electrophysiological screening was assessed by univariate and multivariate analyses correcting for weakness and other risk factors and the prediction model involved only a development phase.Results: A total of 730 patients were electrophysiologically screened of whom 432 were tested for weakness. On day 8, normal CMAP excluded weakness with a high NPV (80.5 %). By day 15, abnormal SNAP and the presence of SEA had a high PPV (91.7 and 80.0 %, respectively). Only a reduced CMAP on day 8 was associated with higher 1-year mortality [35.6 vs 15.2 % (p < 0.001)]. This association remained significant after correction for weakness and other risk factors [OR 2.463 (95 % CI 1.113-5.452), p = 0.026]. Also among conscious/cooperative patients without weakness, reduced CMAP was independently associated with a higher likelihood of death occurring during 1 year [HR 2.818 (95 % CI 1.074-7.391), p = 0.035].Conclusions: The diagnostic properties of electrophysiological screening vary over time. Abnormal CMAP documented early during critical illness carries information about longer-term outcome, which should be further investigated mechanistically. [ABSTRACT FROM AUTHOR]

Background: Critically ill patients typically present with low or low-normal plasma thyroxine, low plasma triiodothyronine (T3), increased plasma reverse T3 (rT3) concentrations, in the absence of a rise in thyrotropin (TSH). This constellation is referred to as nonthyroidal illness syndrome (NTI). Although it is long known that the severity of NTI is associated with risk of poor outcomes of critical illness, the causality in this association has not been well investigated. Summary: In this narrative review, the different faces of NTI during critical illness are highlighted. Acute alterations are dominated by changes in thyroid hormone binding, peripheral thyroid hormone uptake, and alterations in the expression and activity of the type-1 and type-3 deiodinases. It was recently shown that at least part of these acute changes are brought about by concomitant macronutrient restriction, and this part appears adaptive and beneficial. However, the face of the NTI in the prolonged phase of critical illness is different, when patients are fully fed but continue to depend on intensive medical care. In that prolonged phase of illness, hypothalamic thyrotropin releasing hormone (TRH) expression is suppressed and explains reduced TSH secretion and whereby reduced thyroidal hormone release. During prolonged critical illness, and in the presence of adequate nutrition, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type-2 deiodinase activity, and increased sensitivity at the receptor level. Infusing hypothalamic releasing factors in these prolonged critically ill patients can reactivate the thyroid axis and induce an anabolic response. Conclusions: It is clear that the name 'NTI' during critical illness refers to a syndrome with different faces. Tolerating the early 'fasting response' to critical illness and its concomitant changes in thyroid hormone parameters appears to be wise and beneficial. This thus applies to the NTI present in the majority of the patients treated in intensive care units. However, the NTI that occurs in prolonged critically ill patients appears different with regard to both its causes and consequences. Future studies should specifically target this selected population of prolonged critically ill patients, and, after excluding iatrogic drug interferences, investigate the effect on outcome of treatment with hypothalamic releasing factors in adequately powered randomized controlled trials. [ABSTRACT FROM AUTHOR]

Importance: Intensive care unit (ICU)-acquired muscle wasting is a devastating complication leading to persistent weakness and functional disability. The mechanisms of this myopathy are unclear, but a disturbed balance of myosin heavy chain (MyHC) is implicated. Objective: To investigate pathways of myosin turnover in severe critically ill patients at high risk of ICU-acquired weakness. Design: Prospective, mechanistic, observational study. Setting: Interdisciplinary ICUs of a university hospital. Participants: Twenty-nine patients with Sequential Organ Failure Assessment (SOFA) scores of at least 8 on three consecutive days within the first 5 days in ICU underwent two consecutive open skeletal muscle biopsies from the vastus lateralis at median days 5 and 15. Control biopsy specimens were from healthy subjects undergoing hip-replacement surgery. Interventions: None. Main outcome(s) and measure(s): Time-dependent changes in myofiber architecture, MyHC synthesis, and degradation were determined and correlated with clinical data. Results: ICU-acquired muscle wasting was characterized by early, disrupted myofiber ultrastructure followed by atrophy of slow- and fast-twitch myofibers at later time points. A rapid decrease in MyHC mRNA and protein expression occurred by day 5 and persisted at day 15 ( P < 0.05). Expression of the atrophy genes MuRF- 1 and Atrogin1 was increased at day 5 ( P < 0.05). Early MuRF-1 protein content was closely associated with late myofiber atrophy and the severity of weakness. Conclusions and relevance: Decreased synthesis and increased degradation of MyHCs contribute to ICU-acquired muscle wasting. The rates and time frames suggest that pathogenesis of muscle failure is initiated very early during critical illness. The persisting reduction of MyHC suggests that sustained treatment is required. [ABSTRACT FROM AUTHOR]

Background: In critically ill children, omitting early use of parenteral nutrition (late-PN versus early-PN) reduced infections, accelerated weaning from mechanical ventilation, and shortened PICU stay. We hypothesized that fasting-induced ketogenesis mediates these benefits.Methods: In a secondary analysis of the PEPaNIC RCT (N = 1440), the impact of late-PN versus early-PN on plasma 3-hydroxybutyrate (3HB), and on blood glucose, plasma insulin, and glucagon as key ketogenesis regulators, was determined for 96 matched patients staying ≥ 5 days in PICU, and the day of maximal 3HB-effect, if any, was identified. Subsequently, in the total study population, plasma 3HB and late-PN-affected ketogenesis regulators were measured on that average day of maximal 3HB effect. Multivariable Cox proportional hazard and logistic regression analyses were performed adjusting for randomization and baseline risk factors. Whether any potential mediator role for 3HB was direct or indirect was assessed by further adjusting for ketogenesis regulators.Results: In the matched cohort (n = 96), late-PN versus early-PN increased plasma 3HB throughout PICU days 1-5 (P < 0.0001), maximally on PICU day 2. Also, blood glucose (P < 0.001) and plasma insulin (P < 0.0001), but not glucagon, were affected. In the total cohort (n = 1142 with available plasma), late-PN increased plasma 3HB on PICU day 2 (day 1 for shorter stayers) from (median [IQR]) 0.04 [0.04-0.04] mmol/L to 0.75 [0.04-2.03] mmol/L (P < 0.0001). The 3HB effect of late-PN statistically explained its impact on weaning from mechanical ventilation (P = 0.0002) and on time to live PICU discharge (P = 0.004). Further adjustment for regulators of ketogenesis did not alter these findings.Conclusion: Withholding early-PN in critically ill children significantly increased plasma 3HB, a direct effect that statistically mediated an important part of its outcome benefit. [ABSTRACT FROM AUTHOR]

Medical nutrition therapy in critically ill patients remains challenging, not only because of the pronounced stress response with a higher risk for complications, but also due to their heterogeneity evolving from different phases of illness. The present review aims to address current knowledge and guidelines in order to summarize how they can be best implemented into daily clinical practice. Further studies are urgently needed to answer such important questions as best timing, route, dose, and composition of medical nutrition therapy for critically ill patients and to determine how to assess and to adapt to patients' individual needs. [ABSTRACT FROM AUTHOR]

Background: Initiating parenteral nutrition (PN) within 24 h in critically ill children is inferior to withholding PN during the first week, as was found in the PEPaNIC study. The aims of this study were to investigate de-implementation of early initiation of PN at PICUs worldwide, and to identify factors influencing de-implementation.Methods: A cross-sectional online survey was conducted (May - October 2017), consisting of 41 questions addressing current PN practices, the degree of de-implementation, and factors affecting de-implementation.Results: We analysed 81 responses from 39 countries. Of these 81 respondents, 53 (65%) were aware of the findings of the PEPaNIC study, and 43 (53%) have read the article. In these 43 PICUs, PN was completely withheld during the first week in 10 PICUs, of which 5 already withheld PN (12%), and 5 de-implemented early initiation of PN (12%). Partial de-implementation was reported by 17 (40%) and no de-implementation by 16 (37%). Higher de-implementation rates were observed when the interpreted level of evidence and grade of recommendation of PEPaNIC was high. Predominant reasons for retaining early initiation of PN were concerns on withholding amino acids, the safety in undernourished children and neonates, and the long-term consequences. Furthermore, the respondents were waiting for updated guidelines.Conclusions: One year after the publication of the PEPaNIC trial, only two-thirds of the respondents was aware of the study results. Within this group, early initiation of PN was de-implemented completely in 12% of the PICUs, while 40% asserted partial de-implementation. Increasing the awareness, addressing the intervention-specific questions and more frequently revising international guidelines might help to accelerate de-implementation of ineffective, unproven or harmful healthcare. [ABSTRACT FROM AUTHOR]

In critically ill children admitted to pediatric intensive care units (PICUs), enteral nutrition (EN) is often delayed due to gastrointestinal dysfunction or interrupted. Since a macronutrient deficit in these patients has been associated with adverse outcomes in observational studies, supplemental parenteral nutrition (PN) in PICUs has long been widely advised to meeting nutritional requirements. However, uncertainty of timing of initiation, optimal dose and composition of PN has led to a wide variation in previous guidelines and current clinical practices. The PEPaNIC (Early versus Late Parenteral Nutrition in the Pediatric ICU) randomized controlled trial recently showed that withholding PN in the first week in PICUs reduced incidence of new infections and accelerated recovery as compared with providing supplemental PN early (within 24 hours after PICU admission), irrespective of diagnosis, severity of illness, risk of malnutrition or age. The early withholding of amino acids in particular, which are powerful suppressors of intracellular quality control by autophagy, statistically explained this outcome benefit. Importantly, two years after PICU admission, not providing supplemental PN early in PICUs did not negatively affect mortality, growth or health status, and significantly improved neurocognitive development. These findings have an important impact on the recently issued guidelines for PN administration to critically ill children. In this review, we summarize the most recent literature that provides evidence on the implications for clinical practice with regard to the use of early supplemental PN in critically ill children. [ABSTRACT FROM AUTHOR]