Week Of Critical Illness Research Articles

Time-Dependent Variation in Immunoparalysis Biomarkers Among Patients with Sepsis and Critical Illness.

Immunoparalysis is a significant concern in patients with sepsis and critical illness, potentially leading to increased risk of secondary infections. This study aimed to perform a longitudinal assessment of immune function over the initial two weeks following the onset of sepsis and critical illness. We compared ex vivo stimulated cytokine release to traditional markers of immunoparalysis, including monocyte Human Leukocyte Antigen (mHLA)-DR expression and absolute lymphocyte count (ALC). A total of 64 critically ill patients were recruited in a tertiary care academic medical setting, including 31 septic and 33 non-septic patients. Results showed that while mHLA-DR expression significantly increased over time, this was primarily driven by the non-septic subset of critically ill patients. ALC recovery was more prominent in septic patients. Ex vivo stimulation revealed significant increases in TNF and IL-6 production over time in septic patients. However, IFNγ production varied with the stimulant used and did not show significant recovery when normalized to cell count. No significant correlation was found between mHLA-DR expression and other immunoparalysis biomarkers. These findings suggest the need for more nuanced immune monitoring approaches beyond the traditional 'sepsis' versus 'non-sepsis' classifications in critically ill patients. It also provided further evidence of a potential window for targeted immunotherapeutic interventions in the first week of critical illness.

Forecasting disease trajectories in critical illness: comparison of probabilistic dynamic systems to static models to predict patient status in the intensive care unit

ObjectiveConventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk...

Enhanced exclusive enteral nutrition delivery during the first 7 days is associated with decreased 28-day mortality in critically ill patients with normal lactate level: a post hoc analysis of a multicenter randomized trial

Background and aimsExclusive enteral nutrition (EN) is often observed during the first week of ICU admission because of the extra costs and safety considerations for early parenteral nutrition. This study aimed to assess the association between nutrition intake and 28-day mortality in critically ill patients receiving exclusive EN.MethodsThis is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion.ResultsOverall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3–19.6) kcal/kg and 0.6 (0.4–0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768–0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770–0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674–0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672–0.962) for protein delivery, respectively), but not in those > 2 mmol/L.ConclusionsDuring the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L.Trial registration: ISRCTN12233792, registered on November 24, 2017.

Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator.

Pneumonia develops frequently after major surgery and polytrauma and thus in the presence of systemic inflammatory response syndrome (SIRS) and organ dysfunction. Immune checkpoints balance self-tolerance and immune activation. Altered checkpoint blood levels were reported for sepsis. We analyzed associations of pneumonia incidence in the presence of SIRS during the first week of critical illness and trends in checkpoint blood levels. Patients were studied from day two to six after admission to a surgical intensive care unit (ICU). Blood was sampled and physician experts retrospectively adjudicated upon the presence of SIRS and Sepsis-1/2 every eight hours. We measured the daily levels of immune checkpoints and inflammatory markers by bead arrays for polytrauma patients developing pneumonia. Immune checkpoint time series were additionally determined for clinically highly similar polytrauma controls remaining infection-free during follow-up. We performed cluster analyses. Immune checkpoint time trends in cases and controls were compared with hierarchical linear models. For patients with surgical trauma and with and without sepsis, selected immune checkpoints were determined in study baseline samples. In polytrauma patients with post-injury pneumonia, eleven immune checkpoints dominated subcluster 3 that separated subclusters 1 and 2 of myeloid markers from subcluster 4 of endothelial activation, tissue inflammation, and adaptive immunity markers. Immune checkpoint blood levels were more stable in polytrauma cases than controls, where they trended towards an increase in subcluster A and a decrease in subcluster B. Herpes virus entry mediator (HVEM) levels (subcluster A) were lower in cases throughout. In unselected surgical patients, sepsis was not associated with altered HVEM levels at the study baseline. Pneumonia development after polytrauma until ICU-day six was associated with decreased blood levels of HVEM. HVEM signaling may reduce pneumonia risk by strengthening myeloid antimicrobial defense and dampening lymphoid-mediated tissue damage. Future investigations into the role of HVEM in pneumonia and sepsis development and as a predictive biomarker should consider the etiology of critical illness and the site of infection.

Inflammation and altered metabolism impede efficacy of functional electrical stimulation in critically ill patients

BackgroundCritically ill patients suffer from acute muscle wasting, which is associated with significant physical functional impairment. We describe data from nested muscle biopsy studies from two trials of functional electrical stimulation (FES) that did not shown improvements in physical function.MethodsPrimary cohort: single-centre randomized controlled trial. Additional healthy volunteer data from patients undergoing elective hip arthroplasty. Validation cohort: Four-centre randomized controlled trial. Intervention: FES cycling for 60-90min/day. Analyses: Skeletal muscle mRNA expression of 223 genes underwent hierarchal clustering for targeted analysis and validation.ResultsPositively enriched pathways between healthy volunteers and ICU participants were “stress response”, “response to stimuli” and “protein metabolism”, in keeping with published data. Positively enriched pathways between admission and day 7 ICU participants were “FOXO-mediated transcription” (admission = 0.48 ± 0.94, day 7 = − 0.47 ± 1.04 mean log2 fold change; P = 0.042), “Fatty acid metabolism” (admission = 0.50 ± 0.67, day 7 = 0.07 ± 1.65 mean log2 fold change; P = 0.042) and “Interleukin-1 processing” (admission = 0.88 ± 0.50, day 7 = 0.97 ± 0.76 mean log2 fold change; P = 0.054). Muscle mRNA expression of UCP3 (P = 0.030) and DGKD (P = 0.040) decreased in both cohorts with no between group differences. Changes in IL-18 were not observed in the validation cohort (P = 0.268). Targeted analyses related to intramuscular mitochondrial substrate oxidation, fatty acid oxidation and intramuscular inflammation showed PPARγ-C1α; (P < 0.001), SLC25A20 (P = 0.017) and UCP3 (P < 0.001) decreased between admission and day 7 in both arms. LPIN-1 (P < 0.001) and SPT1 (P = 0.044) decreased between admission and day 7. IL-18 (P = 0.011) and TNFRSF12A (P = 0.009) increased in both arms between admission and day 7. IL-1β (P = 0.007), its receptor IL-1R1 (P = 0.005) and IL-6R (P = 0.001) decreased in both arms between admission and day 7. No between group differences were seen in any of these (all p > 0.05).ConclusionsIntramuscular inflammation and altered substrate utilization are persistent in skeletal muscle during first week of critical illness and are not improved by the application of Functional Electrical Stimulation-assisted exercise. Future trials of exercise to prevent muscle wasting and physical impairment are unlikely to be successful unless these processes are addressed by other means than exercise alone.

Glucometrics in the first week of critical illness and its association with mortality

Evaluation of glucometrics in the first week of ICU stay and its association with outcomes. Prospective observational study. Mixed ICU of teaching hospital. Adults initiated on insulin infusion for 2 consecutive blood glucose (BG) readings ≥180 mg/dL. Glucometrics calculated from the BG of first week of admission: hyperglycemia (BG > 180 mg/dL) and hypoglycemia (BG < 70 mg/dL) episodes; median, standard deviation (SD) and coefficient of variation (CV) of BG, glycemic lability index (GLI), time in target BG range (TIR). Factors influencing glucometrics and the association of glucometrics to patient outcomes analyzed. A total of 5762 BG measurements in 100 patients of median age 55 years included. Glucometrics: hyperglycemia: 2253 (39%), hypoglycemia: 28 (0.48%), median BG: 169 mg/dL (162–178.75), SD 31 mg/dL (26–38.75), CV 18.6% (17.1–22.5), GLI: 718.5 [(mg/dL) 2 /h]/week (540.5–1131.5) and TIR 57% (50–67). Diabetes and higher APACHE II score were associated with higher SD and CV, and lower TIR. On multivariate regression, diabetes ( p = 0.009) and APACHE II score ( p = 0.016) were independently associated with higher SD. Higher SD and CV were associated with less vasopressor-free days; lower TIR with more blood-stream infections (BSI). Patients with higher SD, CV and GLI had a higher 28-day mortality. On multivariate analysis, GLI alone was associated with a higher mortality (OR 2.99, p = 0.04). Glycemic lability in the first week in ICU patients receiving insulin infusion is associated with higher mortality. Lower TIR is associated with more blood stream infections. Evaluación de la glucometría en la primera semana de estancia en la UCI y su asociación con los resultados. Estudio observacional prospectivo. UCI mixta de hospital docente. Adultos que iniciaron una infusión de insulina para dos lecturas consecutivas de glucosa en sangre (GS) ≥ 180 mg/dl. Glucometría calculada a partir de la GS de la primera semana de ingreso: episodios de hiperglucemia (GS > 180 mg/dl) e hipoglucemia (GS < 70 mg/dl); mediana, desviación estándar (DE) y coeficiente de variación (CV) de GS, índice de labilidad glucémica (ILG), tiempo en el rango objetivo de GS (TIR). Se incluyeron un total de 5.762 GS en 100 pacientes con una mediana de edad de 55 años. Glucometría: hiperglucemia: 2.253 (39%), hipoglucemia: 28 (0,48%), mediana GS: 169 mg/dl, DE 31 mg/dl, CV 18,6%, ILG: 718,5 [(mg/dl)2/h]/semana, TIR 57%. La diabetes y una puntuación APACHE II más alta se asociaron con una DE y un CV más altos y una TIR más baja. En la regresión multivariada, la diabetes (p = 0,009) y la puntuación APACHE II (p = 0,016) se asociaron de forma independiente con una DE más alta. La DE y el CV más altos se asociaron con menos días sin vasopresores; menor TIR, con más infecciones del torrente sanguíneo (ITS). En el análisis multivariado, el ILG solo se asoció con una mayor mortalidad (OR: 2,99, p = 0,04). La labilidad glucémica en la primera semana en pacientes de UCI que reciben infusión de insulina se asocia con mayor mortalidad. Una TIR más baja se asocia con más ITS.

Immunoparalysis in critically ill children.

Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university-affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)-DR expression and tumour necrosis factor (TNF)-α and interleukin (IL)-6 production were measured by flow-cytometry at three time points (T1=1-2 days; T2=3-5 days; T3=6-8 days). Using the paediatric logistic organ dysfunction-2 score to assess initial disease severity, we established the optimal cut-off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA-DR ≤ 1758.5, area under the curve (AUC)=0.775; and frequency of monocytes producing IL-6 ≤ 68.5%, AUC=0.905) or in T3 (classical monocytes MFI of HLA-DR ≤ 2587.5, AUC=0.675; and frequency of monocytes producing TNF-α ≤ 93.5%, AUC=0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p= 0.011), vasoactive inotropic score (p= 0.014) and length of hospital stay (p= 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n= 5), patients showed higher percentages of non-classical monocytes (p= 0.004). No mortality was recorded. A reduction in classical monocytes HLA-DR expression with lower frequencies of monocytes producing TNF-α and IL-6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non-classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.

Glucometrics in the first week of critical illness and its association with mortality

ObjectiveEvaluation of glucometrics in the first week of ICU stay and its association with outcomes. DesignProspective observational study. SettingMixed ICU of teaching hospital. PatientsAdults initiated on insulin infusion for 2 consecutive blood glucose (BG) readings ≥180mg/dL. Main variables of interestGlucometrics calculated from the BG of first week of admission: hyperglycemia (BG>180mg/dL) and hypoglycemia (BG<70mg/dL) episodes; median, standard deviation (SD) and coefficient of variation (CV) of BG, glycemic lability index (GLI), time in target BG range (TIR). Factors influencing glucometrics and the association of glucometrics to patient outcomes analyzed. ResultsA total of 5762 BG measurements in 100 patients of median age 55 years included. Glucometrics: hyperglycemia: 2253 (39%), hypoglycemia: 28 (0.48%), median BG: 169mg/dL (162–178.75), SD 31mg/dL (26–38.75), CV 18.6% (17.1–22.5), GLI: 718.5 [(mg/dL)2/h]/week (540.5–1131.5) and TIR 57% (50–67).Diabetes and higher APACHE II score were associated with higher SD and CV, and lower TIR. On multivariate regression, diabetes (p=0.009) and APACHE II score (p=0.016) were independently associated with higher SD.Higher SD and CV were associated with less vasopressor-free days; lower TIR with more blood-stream infections (BSI). Patients with higher SD, CV and GLI had a higher 28-day mortality. On multivariate analysis, GLI alone was associated with a higher mortality (OR 2.99, p=0.04). ConclusionsGlycemic lability in the first week in ICU patients receiving insulin infusion is associated with higher mortality. Lower TIR is associated with more blood stream infections.

Nutrition support for critically ill patients.

Nutrition support is an important aspect of the management of critically ill patients. This review highlights the emerging evidence on critical care nutrition and focuses on the pathophysiologic interplay between critical illness, the gastrointestinal tract, and nutrition support and the evidence on the best route, dose, and timing of nutrition. Although indirect calorimetry is recommended to measure energy expenditure, predictive equations are commonly used but are limited by their inaccuracy in individual patients. The current evidence supports early enteral nutrition (EN) in most patients, with a gradual increase in the daily dose over the first week. Delayed EN is warranted in patients with severe shock. According to recent trials, parenteral nutrition seems to be as effective as EN and may be started if adequate EN is not achieved by the first week of critical illness. A high protein dose has been recommended, but the best timing is unclear. Immuno-nutrition should not be routinely provided to critically ill patients. Patients receiving artificial nutrition should be monitored for metabolic derangements. Additional adequately powered studies are still needed to resolve many unanswered questions.

P0154 / #2091: EXOCRINE PANCREATIC FUNCTION IN CRITICALLY ILL PEDIATRIC PATIENTS

Aims & Objectives: To determine the exocrine pancreatic function of critically ill children. Methods: Prospective observational study conducted in the PICU of a tertiary hospital in Madrid, Spain. Children admitted to PICU whose expected PICU length of stay was more than one week were enrolled. Fecal elastase-1, amylase levels were analyzed on admission, day 7 and discharge. Stool samples were taken in the first week of hospitalization to analyze fecal elastase-1 by immunochromatographic tests. Elastase-1 concentration of 1-2 μg/g was considered normal, whereas levels <1 μg/g revealed exocrine pancreas dysfunction. Results: 15 critically ill children were enrolled in the study with a median age of 5 months (IQR 4-20 months). The median PRISM III was 9 (IQR 6-16) and the median length of PICU stay was 15 days (IQR 9-63). Two of them died and only one of them developed diarrhea during the study period. Fecal elastase-1 was collected in 10 children and was normal in all of them. Mean amylase levels on admission, on day 7 and at PICU discharge were 13 U/L (IQR 6.5-41.5), 16 U/L (IQR 4.8-61.5) and 15.5 U/L (IQR 7-44) respectively. Mean lipase levels on admission, on day 7 and at PICU discharge were 11 U/L (IQR 6.8-19.5) 14 U/L (IQR 11-28) and 16.5 U/L (IQR 12.3-36.8). Conclusions: Exocrine pancreatic function seems to be normal during the first week of critical illness in children. More studies including a higher number of patients and using more specific test are required to confirm these results.

Supplementation of vitamins, trace elements and electrolytes in the PEPaNIC Randomised Controlled Trial: Composition and preparation of the prescription.

Following the results of the paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial, the new ESPGHAN/ESPEN/ESPR/CSPEN and ESPNIC guidelines recommend to consider withholding parenteral macronutrients for 1 week, while providing micronutrients, in critically ill children if enteral nutrition is insufficient. Critically ill children are suspected to be vulnerable to micronutrient deficiencies due to inadequate enteral nutrition, increased body's demands and excessive losses. Hitherto, micronutrient requirements in PICU are estimated based on recommended daily intakes for healthy children and expert opinion. We aimed to provide an overview of the current practice of micronutrient administration and practical considerations in the three participating centres of the PEPaNIC study, and compare these therapies with the recommendations in the new ESPGHAN/ESPEN/ESPR/CSPEN guidelines. We describe the current composition and preparation of the prescribed parenteral micronutrients (consisting of vitamins, trace elements and electrolytes) in the three centres (Leuven, Rotterdam and Edmonton) that participated in the PEPaNIC RCT, and compare this per micronutrient with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines recommendations. The three centres use a different micronutrient supplementation protocol during the first week of critical illness in children, with substantial differences regarding the amounts administered. Leuven administers commercial vitamins, trace elements and electrolytes in separate infusions both in 4h. Rotterdam provides commercial vitamins and trace elements simultaneously via 8-h infusion and electrolytes continuously over 24h. Lastly, Edmonton administers commercial vitamins and institutionally prepared trace elements solutions in 1h and electrolytes on demand. Comparison with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines yields in differences between the recommendations and the administered amounts, which are most substantial for vitamins. The practice of intravenous micronutrient administration differs substantially between the three PEPaNIC centres and in comparison with the current guideline recommendations. This deviation is at least partially explained by the inability to provide all recommended amounts with the currently available commercial products and by the lack of strong evidence supporting these recommendations.

Editorial: Five false arguments for using parenteral nutrition during the first week of critical illness

Editorial: Five false arguments for using parenteral nutrition during the first week of critical illness

Enteral nutrition during the acute phase in critically ill children: association with patient characteristics and clinical outcome

Rationale: Current enteral nutrition (EN) guidelines for critically ill children are largely based on observational studies in which the inability to achieve EN targets has been associated with impaired outcome. Our aim was to evaluate the associations between EN intake and 1) patient characteristics and daily clinical variables; and 2) clinical outcomes adjusted for these patient and clinical characteristics during the first week of critical illness.

The role of parenteral nutrition in paediatric critical care, and its consequences on recovery

: The goal of nutritional support during critical illness is to provide the appropriate amount of nutrition accounting for the acute, stable and recovery phase in order to accelerate recovery and to improve short-term and long-term outcomes. Although the preferred route to provide nutritional support during paediatric critical illness is via enteral route, reaching target intakes is often difficult due to (perceived) feeding intolerance, fluid restriction, and interruptions around procedures. Because undernourishment in these children has been associated with impaired outcome, parenteral nutrition (PN) has therefore been viewed as an optimal alternative for reaching early and high nutritional targets. However, PN recommendations regarding timing, dose and composition varied widely and were based on studies using intermediate or surrogate endpoints and observational studies. It was not until the paediatric early versus late PN in critically ill children (PEPaNIC) randomized controlled trial (RCT) that the advice to reach high and early macronutrient goals via PN was challenged. The PEPaNIC study showed that omitting supplemental PN during the first week of paediatric intensive care unit (PICU) admission as compared with early initiation of PN (<24 hours) reduced new acquired infections and accelerated recovery. The provision of amino acids in particular was negatively associated with short-term outcomes, probably explained by the suppression of the activation of autophagy. Autophagy is an evolutionary conserved intracellular degradation process and it is crucial for maintaining cellular integrity and function, which becomes even more important during acute stress. Results of the long-term PEPaNIC follow-up study showed that withholding early PN did not negatively affect anthropometrics and health status but improved neurocognitive and psychosocial development 2 and 4 years later. Current guidelines therefore advise to consider withholding parenteral macronutrients for the first week of PICU admission, while providing micronutrients. Although parenteral restriction during the first week of critical illness has been found beneficial, further research beyond the acute phase is warranted to determine the best role of PN in terms of optimal timing, dose and composition in order to improve short-term recovery and long-term developmental outcomes.

Achieving enteral nutrition during the acute phase in critically ill children: Associations with patient characteristics and clinical outcome

In the absence of methodologically sound randomized controlled trials (RCTs), current recommendations for timing and amount of enteral nutrition (EN) in critically ill children are based on observational studies. These studies have associated achievement of a higher EN intake in critically ill children with improved outcome. Inherent to the observational design of these underlying studies, thorough insight in possible confounding factors to correct for is essential. We evaluated the associations between EN intake and 1) patient and daily clinical characteristics and 2) clinical outcomes adjusted for these patient and clinical characteristics during the first week of critical illness with a multivariable mixed model. This secondary analysis of the multicentre PEPaNIC RCT investigated a subgroup of critically ill children with daily prospectively recorded gastrointestinal symptoms and EN intake during the first week with multivariable analyses using two-part mixed effect models, including multiple testing corrections using Holm's method. These models combined a mixed-effects logistic regression for the dichotomous outcome EN versus no EN, and a linear mixed-effects model for the patients who received any EN intake. EN intake per patient was expressed as mean daily EN as % of predicted resting energy expenditure (% of EN/REE). Model 1 included 40 fixed effect baseline patient characteristics, and daily parameters of illness severity, feeding, medication and gastrointestinal symptoms. Model 2 included these patient and daily variables as well as clinical outcomes. Complete data were available for 690 children. EN was provided in 503 (73%) patients with a start after a median of 2 (IQR 2-3) days and a median % of EN/REE of 38.8 (IQR 14.1-79.5) over the first week. Multivariable mixed model analyses including all patients showed that admission after gastrointestinal surgery (-49%EN/REE; p=0.002), gastric feeding (-31% EN/REE; p<0.001), treatment with inotropic agents (-22%EN/REE; p=0.026) and large gastric residual volume (-64%EN/REE; p<0.001) were independently associated with a low mean EN intake. In univariable analysis, low mean EN intake was associated with new acquired infections, hypoglycaemia, duration of PICU and hospital stay and duration of mechanical ventilation. However, after adjustment for confounders, these associations were no longer present, except for low EN and hypoglycaemia (-39%EN/REE; p=0.018). Several patient and clinical characteristics during the first week of critical illness were associated with EN intake. No independent associations were found between EN intake and clinical outcomes such as mortality, new acquired infection and duration of stay. These data emphasize the necessity of adequate multivariable adjustment in nutritional support research and the need for future RCTs investigating optimal EN intake.

Association between ultrasound quadriceps muscle status with premorbid functional status and 60-day mortality in mechanically ventilated critically ill patient: A single-center prospective observational study

In critically ill patients, direct measurement of skeletal muscle using bedside ultrasound (US) may identify a patient population that might benefit more from optimal nutrition practices. When US is not available, survey measures of nutrition risk and functional status that are associated with muscle status may be used to identify patients with low muscularity. This study aims to determine the association between baseline and changing ultrasound quadriceps muscle status with premorbid functional status and 60-day mortality. This single-center prospective observational study was conducted in a general ICU. Mechanically ventilated critically ill adult patients (age≥18 years) without pre-existing systemic neuromuscular diseases and expected to stay for ≥96h in the ICU were included. US measurements were performed within 48h of ICU admission (baseline), at day 7, day 14 of ICU stay and at ICU discharge (if stay >14 days). Quadriceps muscle layer thickness (QMLT), rectus femoris cross sectional area (RFCSA), vastus intermedius pennation angle (PA) and fascicle length (FL), and rectus femoris echogenicity (mean and standard deviation [SD]) were measured. Patients' next-of-kin were interviewed by using established questionnaires for their pre-hospitalization nutritional risk (nutrition risk screening-2002) and functional status (SARC-F, clinical frailty scale [CFS], Katz activities of daily living [ADL] and Lawton Instrumental ADL). Ninety patients were recruited. A total of 86, 53, 24 and 10 US measures were analyzed, which were performed at a median of 1, 7, 14 and 22 days from ICU admission, respectively. QMLT, RFCSA and PA reduced significantly over time. The overall trend of change of FL was not significant. The only independent predictor of 60-day mortality was the change of QMLT from baseline to day 7 (adjusted odds ratio 0.95 for every 1% less QMLT loss, 95% confidence interval 0.91-0.99; p=0.02). Baseline measures of high nutrition risk (modified nutrition risk in critically ill ≥5), sarcopenia (SARC-F≥4) and frailty (CFS≥5) were associated with lower baseline QMLT, RFCSA and PA and higher 60-day mortality. Every 1% loss of QMLT over the first week of critical illness was associated with 5% higher odds of 60-day mortality. SARC-F, CFS and mNUTRIC are associated with quadriceps muscle status and 60-day mortality and may serve as a potential simple and indirect measures of premorbid muscle status at ICU admission.

Health-related quality of life of children and their parents 2 years after critical illness: pre-planned follow-up of the PEPaNIC international, randomized, controlled trial

BackgroundPediatric 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.MethodsChildren 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.ResultsFor 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.ConclusionsParent-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 registrationClinical trials, NCT01536275. Registered 22 February 2012

Narrowing the Protein Deficit Gap in Critically Ill Patients Using a Very High-Protein Enteral Formula.

Protein deficits have been associated with longer intensive care unit (ICU) stays and increased mortality. Current view suggests if protein goals are met, meeting full energy targets may be less important and prevent deleterious effects of overfeeding. We proposed a very-high protein (VHP) enteral nutrition (EN) formula could provide adequate protein, without overfeeding energy, in the first week of critical illness. This was a retrospective study of medical/surgical ICU patients receiving EN exclusively for ≥5 days during the first week of ICU admission. Twenty participants received standard EN; 20 participants received the VHP-EN formula (1 kcal/mL, 37% protein). Protein and energy prescribed/received, gastrointestinal tolerance, and feeding interruptions were examined. Forty ICU patients [average Acute Physiology and Chronic Health Evaluation II score of 20.1] were included. Protein prescribed and received was significantly higher in the VHP group vs the standard EN group (135.5 g/d ± 22.9 vs 111.4 g/d ± 25; P = .003 and 112.2 g/d ± 27.8 vs 81.7 g/d ± 16.7, respectively; P = .002). Energy prescribed and received was similar between groups (1696 kcal/d ± 402 vs 1893 kcal/d ± 341, respectively; P = .101 and 1520 kcal/d ± 346 vs 1506 ± 380 kcal/d; P = .901). There were no differences in EN tolerance (P = .065) or feeding interruptions (P = .336). Use of a VHP formula in ICU patients resulted in higher protein intakes without overfeeding energy or use of modular protein in the first 5 days of exclusive EN.

Acquired neuromuscular weakness In Intensive Care Unit: Review article

A substantial number of patients admitted to the ICU because of an acute illness, complicated surgery, severe trauma, or burn injury will develop a de novo form of muscle weakness during the ICU stay that is referred to as “intensive care unit acquired weakness” (ICUAW). This ICUAW evoked by critical illness can be due to axonal neuropathy, primary myopathy, or both. Underlying pathophysiological mechanisms comprise microvascular, electrical, metabolic, and bioenergetic alterations, interacting in a complex way and culminating in loss of muscle strength and/or muscle atrophy. ICUAW is typically symmetrical and affects predominantly proximal limb muscles and respiratory muscles, whereas facial and ocular muscles are often spared. ICUAW is diagnosed in awake and cooperative patients by bedside manual testing of muscle strength and the severity is scored by the Medical Research Council sum score. In cases of atypical clinical presentation or evolution, additional electrophysiological testing may be required for differential diagnosis. The cornerstones of prevention are aggressive treatment of sepsis, early mobilization, preventing hyperglycemia with insulin, and avoiding the use parenteral nutrition during the first week of critical illness. Future research should focus on new preventive and/or therapeutic strategies for this detrimental complication of critical illness and on clarifying how ICUAW contributes to poor longer-term prognosis.

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

BackgroundTo better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study.MethodsThis is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1–2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort.ResultsOf the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1–Q3, 7–21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample.ConclusionsMost patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality.Trial registrationClinicalTrials.gov, NCT02010073. Registered on 12 December 2013.