High protein provision of more than 1.2 g/kg improves muscle mass preservation and mortality in ICU patients: A systematic review and meta-analyses.

BACKGROUND: ICU patients lose muscle mass rapidly and maintenance of muscle mass may contribute to improved survival rates and quality of life. Protein provision may be beneficial for preservation of muscle mass and other clinical outcomes, including survival. Current protein recommendations are expert-based and range from 1.2 to 2.0 g/kg. Thus, we performed a systematic review and meta-analysis on protein provision and all clinically relevant outcomes recorded in the available literature. METHODS: We conducted a systematic review and meta-analyses, including studies of all designs except case control and case studies, with patients aged ≥18 years with an ICU stay of ≥2 days and a mean protein provision group of ≥1.2 g/kg as compared to <1.2 g/kg with a difference of ≥0.2 g/kg between protein provision groups. All clinically relevant outcomes were studied. Meta-analyses were performed for all clinically relevant outcomes that were recorded in ≥3 included studies. RESULTS: A total of 29 studies published between 2012 and 2022 were included. Outcomes reported in the included studies were ICU, hospital, 28-day, 30-day, 42-day, 60-day, 90-day and 6-month mortality, ICU and hospital length of stay, duration of mechanical ventilation, vomiting, diarrhea, gastric residual volume, pneumonia, overall infections, nitrogen balance, changes in muscle mass, destination at hospital discharge, physical performance and psychological status. Meta-analyses showed differences between groups in favour of high protein provision for 60-day mortality, nitrogen balance and changes in muscle mass. CONCLUSION: High protein provision of more than 1.2 g/kg in critically ill patients seemed to improve nitrogen balance and changes in muscle mass on the short-term and likely 60-day mortality. Data on long-term effects on quality of life are urgently needed.

Visceral obesity measured using computed tomography scans: No significant association with mortality in critically ill patients.

INTRODUCTION: The association between obesity and outcome in critical illness is unclear. Since the amount of visceral adipose tissue(VAT) rather than BMI mediates the health effects of obesity we aimed to investigate the association between visceral obesity, BMI and 90-day mortality in critically ill patients. METHOD: In 555 critically ill patients (68% male), the VAT Index(VATI) was measured using Computed Tomography scans on the level of vertebra L3. The association between visceral obesity, BMI and 90-day mortality was investigated using univariable and multivariable analyses, correcting for age, sex, APACHE II score, sarcopenia and muscle quality. RESULTS: Visceral obesity was present in 48.1% of the patients and its prevalence was similar in males and females. Mortality was similar amongst patients with and without visceral obesity (27.7% vs 24.0%, p = 0.31). The corrected odds ratio of 90-day mortality for visceral obesity was 0.667 (95%CI 0.424-1.049, p = 0.080). Using normal BMI as reference, the corrected odds ratio for overweight was 0.721 (95%CI 0.447-1.164 p = 0.181) and for obesity 0.462 (95%CI 0.208-1.027, p = 0.058). CONCLUSION: No significant association of visceral obesity and BMI with 90-day mortality was observed in critically ill patients, although obesity and visceral obesity tended to be associated with improved 90-day mortality.

Early high protein provision and mortality in ICU patients including those receiving continuous renal replacement therapy.

BACKGROUND: Findings on the association between early high protein provision and mortality in ICU patients are inconsistent. The relation between early high protein provision and mortality in patients receiving CRRT remains unclear. The aim was to study the association between early high protein provision and hospital and ICU mortality and consistency in subgroups. METHODS: A retrospective cohort study was conducted in 2618 ICU patients with a feeding tube and mechanically ventilated ≥48 h (2003-2016). The association between early high protein provision (≥1.2 g/kg/day at day 4 vs. <1.2 g/kg/day) and hospital and ICU mortality was assessed for the total group, for patients receiving CRRT, and for non-septic and septic patients, by Cox proportional hazards analysis. Adjustments were made for APACHE II score, energy provision, BMI, and age. RESULTS: Mean protein provision at day 4 was 0.96 ± 0.48 g/kg/day. A significant association between early high protein provision and lower hospital mortality was found in the total group (HR 0.48, 95% CI 0.39-0.60, p = <0.001), CRRT-receiving patients (HR 0.62, 95% CI 0.39-0.99, p = 0.045) and non-septic patients (HR 0.56, 95% CI 0.44-0.71, p = <0.001). However, no association was found in septic patients (HR 0.71, 95% CI 0.39-1.29, p = 0.264). These associations were very similar for ICU mortality. In a sensitivity analysis for patients receiving a relative energy provision >50%, results remained robust in all groups except for patients receiving CRRT. CONCLUSIONS: Early high protein provision is associated with lower hospital and ICU mortality in ICU patients, including CRRT-receiving patients. There was no association for septic patients.

Monitoring muscle mass using ultrasound: a key role in critical care.

PURPOSE OF REVIEW: The loss of muscle mass in critically ill patients contributes to morbidity and mortality, and results in impaired recovery of physical functioning. The number of publications on the topic is increasing. However, there is a lack of consistent methodology and the most optimal methodology remains unclear, hampering its broad use in clinical practice. RECENT FINDINGS: There is a large variety of studies recently published on the use of ultrasound for assessment of muscle mass. A selection of studies has been made, focusing on monitoring of muscle mass (repeated measurements), practical aspects, feasibility and possible nutrition and physical therapy interventions. In this review, 14 new small (n = 19-121) studies are categorized and reviewed as individual studies. SUMMARY: The use of ultrasound in clinical practice is feasible for monitoring muscle mass in critically ill patients. Assessment of muscle mass by ultrasound is clinically relevant and adds value for guiding therapeutic interventions, such as nutritional and physical therapy interventions to maintain muscle mass and promote recovery in critically ill patients.

Fluid balance and phase angle as assessed by bioelectrical impedance analysis in critically ill patients: a multicenter prospective cohort study.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a validated method to assess body composition in persons with fluid homeostasis and reliable body weight. This is not the case during critical illness. The raw BIA markers resistance, reactance, phase angle, and vector length are body weight independent. Phase angle reflects cellular health and has prognostic significance. We aimed to assess the course of phase angle and vector length during intensive care unit (ICU) admission, and determine the relation between their changes (Δ) and changes in body hydration. METHODS: A prospective, dual-center observational study of adult ICU patients was conducted. Univariate and multivariable regression analyses were performed, including reactance as a marker of cellular mass and integrity and total body water according to the Biasioli equation (TBWBiasioli) and fluid balance as body weight independent markers of hydration. RESULTS: One hundred and fifty-six ICU patients (mean ± SD age 62.5 ± 14.5 years, 67% male) were included. Between days 1 and 3, there was a significant decrease in reactance/m (-2.6 ± 6.0 Ω), phase angle (-0.4 ± 1.1°), and vector length (-12.2 ± 44.3 Ω/m). Markers of hydration significantly increased. Δphase angle and Δvector length were both positively related to Δreactance/m (r2 = 0.55, p < 0.01; r2 = 0.38, p < 0.01). Adding ΔTBWBiasioli as explaining factor strongly improved the association between Δphase angle and Δreactance/m (r2 = 0.73, p < 0.01), and Δvector length and Δreactance/m (r2 = 0.77, p < 0.01). CONCLUSIONS: Our results show that during critical illness, changes in phase angle and vector length partially reflect changes in hydration.

Identifying critically ill patients with low muscle mass: Agreement between bioelectrical impedance analysis and computed tomography.

BACKGROUND & AIMS: Low muscle mass and -quality on ICU admission, as assessed by muscle area and -density on CT-scanning at lumbar level 3 (L3), are associated with increased mortality. However, CT-scan analysis is not feasible for standard care. Bioelectrical impedance analysis (BIA) assesses body composition by incorporating the raw measurements resistance, reactance, and phase angle in equations. Our purpose was to compare BIA- and CT-derived muscle mass, to determine whether BIA identified the patients with low skeletal muscle area on CT-scan, and to determine the relation between raw BIA and raw CT measurements. METHODS: This prospective observational study included adult intensive care patients with an abdominal CT-scan. CT-scans were analysed at L3 level for skeletal muscle area (cm2) and skeletal muscle density (Hounsfield Units). Muscle area was converted to muscle mass (kg) using the Shen equation (MMCT). BIA was performed within 72 h of the CT-scan. BIA-derived muscle mass was calculated by three equations: Talluri (MMTalluri), Janssen (MMJanssen), and Kyle (MMKyle). To compare BIA- and CT-derived muscle mass correlations, bias, and limits of agreement were calculated. To test whether BIA identifies low skeletal muscle area on CT-scan, ROC-curves were constructed. Furthermore, raw BIA and CT measurements, were correlated and raw CT-measurements were compared between groups with normal and low phase angle. RESULTS: 110 patients were included. Mean age 59 ± 17 years, mean APACHE II score 17 (11-25); 68% male. MMTalluri and MMJanssen were significantly higher (36.0 ± 9.9 kg and 31.5 ± 7.8 kg, respectively) and MMKyle significantly lower (25.2 ± 5.6 kg) than MMCT (29.2 ± 6.7 kg). For all BIA-derived muscle mass equations, a proportional bias was apparent with increasing disagreement at higher muscle mass. MMTalluri correlated strongest with CT-derived muscle mass (r = 0.834, p < 0.001) and had good discriminative capacity to identify patients with low skeletal muscle area on CT-scan (AUC: 0.919 for males; 0.912 for females). Of the raw measurements, phase angle and skeletal muscle density correlated best (r = 0.701, p < 0.001). CT-derived skeletal muscle area and -density were significantly lower in patients with low compared to normal phase angle. CONCLUSIONS: Although correlated, absolute values of BIA- and CT-derived muscle mass disagree, especially in the high muscle mass range. However, BIA and CT identified the same critically ill population with low skeletal muscle area on CT-scan. Furthermore, low phase angle corresponded to low skeletal muscle area and -density. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02555670).

Amino Acid Loss during Continuous Venovenous Hemofiltration in Critically Ill Patients.

BACKGROUND/OBJECTIVES: During continuous venovenous hemofiltration (CVVH), there is unwanted loss of amino acids (AA) in the ultrafiltrate (UF). Solutes may also be removed by adsorption to the filter membrane. The aim was to quantify the total loss of AA via the CVVH circuit using a high-flux polysulfone membrane and to differentiate between the loss by ultrafiltration and adsorption. METHODS: Prospective observational study in ten critically ill patients, receiving predilution CVVH with a new filter, blood flow 180 mL/min, and predilution flow 2,400 mL/h. Arterial blood, postfilter blood, and UF samples were taken at baseline, and 1, 8, and 24-h after CVVH initiation, to determine AA concentrations and hematocrit. Mass transfer calculations were used to determine AA loss in the filter and by UF, and the difference between these 2. RESULTS: The median AA loss in the filter was 10.4 g/day, the median AA loss by UF was 13.4 g/day, and the median difference was -2.9 g/day (IQR -5.9 to -1.4 g/day). For the individual AA, the difference ranged from -1 g/day to +0.4 g/day, suggesting that some AA were consumed or adsorbed and others were generated. AA losses did not significantly change over the 24-h study period. CONCLUSION: During CVVH with a modern polysulfone membrane, the estimated AA loss was 13.4 g/day, which corresponds to a loss of about 11.2 g of protein per day. Adsorption did not play a major role. However, individual AA behaved differently, suggesting complex interactions and processes at the filter membrane or peripheral AA production.

Indirect calorimetry in critically ill mechanically ventilated patients: Comparison of E-sCOVX with the deltatrac.

BACKGROUND & AIMS: Indirect calorimetry is recommended to measure energy expenditure (EE) in critically ill, mechanically ventilated patients. The most validated system, the Deltatrac® (Datex-Ohmeda, Helsinki, Finland) is no longer in production. We tested the agreement of a new breath-by-breath metabolic monitor E-sCOVX® (GE healthcare, Helsinki, Finland), with the Deltatrac. We also compared the performance of the E-sCOVX to commonly used predictive equations. METHODS: We included mechanically ventilated patients eligible to undergo indirect calorimetry. After a stabilization period, EE was measured simultaneously with the Deltatrac and the E-sCOVX for 2 h. Agreement and precision of the E-sCOVX was tested by determining bias, limits of agreement and agreement rates compared to the Deltatrac. Performance of the E-sCOVX was also compared to four predictive equations: the 25 kcal/kg, Penn State University 2003b, Faisy, and Harris-Benedict equation. RESULTS: We performed 29 measurements in 16 patients. Mean EE-Deltatrac was 1942 ± 274 kcal/day, and mean EE-E-sCOVX was 2177 ± 319 kcal/day (p < 0.001). E-sCOVX overestimated EE with a bias of 235 ± 149 kcal/day, being 12.1% of EE-Deltatrac. Limits of agreement were -63 to +532 kcal/day. The 10% and 15% agreement rates of EE-E-sCOVX compared to the Deltatrac were 34% and 72% respectively. The bias of E-sCOVX was lower than the bias of the 25 kcal/kg-equation, but higher than bias of the other equations. Agreement rates for E-sCOVX were similar to the equations. The Faisy-equation had the highest 15% agreement rate. CONCLUSION: The E-sCOVX metabolic monitor is not accurate in estimating EE in critically ill mechanically ventilated patients when compared to the Deltatrac, the present reference method. The E-sCOVX overestimates EE with a bias and precision that are clinically unacceptable.

Bioelectrical impedance analysis-derived phase angle at admission as a predictor of 90-day mortality in intensive care patients.

BACKGROUND/OBJECTIVES: A low bioelectrical impedance analysis (BIA)-derived phase angle (PA) predicts morbidity and mortality in different patient groups. An association between PA and long-term mortality in ICU patients has not been demonstrated before. The purpose of the present study was to determine whether PA on ICU admission independently predicts 90-day mortality. SUBJECTS/ METHODS: This prospective observational study was performed in a mixed university ICU. BIA was performed in 196 patients within 24 h of ICU admission. To test the independent association between PA and 90-day mortality, logistic regression analysis was performed using the APACHE IV predicted mortality as confounder. The optimal cutoff value of PA for mortality prediction was determined by ROC curve analysis. Using this cutoff value, patients were categorized into low or normal PA group and the association with 90-day mortality was tested again. RESULTS: The PA of survivors was higher than of the non-survivors (5.0° ± 1.3° vs. 4.1° ± 1.2°, p < 0.001). The area under the ROC curve of PA for 90-day mortality was 0.70 (CI 0.59-0.80). PA was associated with 90-day mortality (OR = 0.56, CI: 0.38-0.77, p = 0.001) on univariate logistic regression analysis and also after adjusting for BMI, gender, age, and APACHE IV on multivariable logistic regression (OR = 0.65, CI: 0.44-0.96, p = 0.031). A PA < 4.8° was an independent predictor of 90-day mortality (adjusted OR = 3.65, CI: 1.34-9.93, p = 0.011). CONCLUSIONS: Phase angle at ICU admission is an independent predictor of 90-day mortality. This biological marker can aid in long-term mortality risk assessment of critically ill patients.

Skeletal muscle quality as assessed by CT-derived skeletal muscle density is associated with 6-month mortality in mechanically ventilated critically ill patients.

BACKGROUND: Muscle quantity at intensive care unit (ICU) admission has been independently associated with mortality. In addition to quantity, muscle quality may be important for survival. Muscle quality is influenced by fatty infiltration or myosteatosis, which can be assessed on computed tomography (CT) scans by analysing skeletal muscle density (SMD) and the amount of intermuscular adipose tissue (IMAT). We investigated whether CT-derived low skeletal muscle quality at ICU admission is independently associated with 6-month mortality and other clinical outcomes. METHODS: This retrospective study included 491 mechanically ventilated critically ill adult patients with a CT scan of the abdomen made 1 day before to 4 days after ICU admission. Cox regression analysis was used to determine the association between SMD or IMAT and 6-month mortality, with adjustments for Acute Physiological, Age, and Chronic Health Evaluation (APACHE) II score, body mass index (BMI), and skeletal muscle area. Logistic and linear regression analyses were used for other clinical outcomes. RESULTS: Mean APACHE II score was 24 ± 8 and 6-month mortality was 35.6%. Non-survivors had a lower SMD (25.1 vs. 31.4 Hounsfield Units (HU); p < 0.001), and more IMAT (17.1 vs. 13.3 cm2; p = 0.004). Higher SMD was associated with a lower 6-month mortality (hazard ratio (HR) per 10 HU, 0.640; 95% confidence interval (CI), 0.552-0.742; p < 0.001), and also after correction for APACHE II score, BMI, and skeletal muscle area (HR, 0.774; 95% CI, 0.643-0.931; p = 0.006). Higher IMAT was not significantly associated with higher 6-month mortality after adjustment for confounders. A 10 HU increase in SMD was associated with a 14% shorter hospital length of stay. CONCLUSIONS: Low skeletal muscle quality at ICU admission, as assessed by CT-derived skeletal muscle density, is independently associated with higher 6-month mortality in mechanically ventilated patients. Thus, muscle quality as well as muscle quantity are prognostic factors in the ICU. TRIAL REGISTRATION: Retrospectively registered (initial release on 06/23/2016) at ClinicalTrials.gov: NCT02817646 .

Ventilator-derived carbon dioxide production to assess energy expenditure in critically ill patients: proof of concept.

INTRODUCTION: Measurement of energy expenditure (EE) is recommended to guide nutrition in critically ill patients. Availability of a gold standard indirect calorimetry is limited, and continuous measurement is unfeasible. Equations used to predict EE are inaccurate. The purpose of this study was to provide proof of concept that EE can be accurately assessed on the basis of ventilator-derived carbon dioxide production (VCO2) and to determine whether this method is more accurate than frequently used predictive equations. METHODS: In 84 mechanically ventilated critically ill patients, we performed 24-h indirect calorimetry to obtain a gold standard EE. Simultaneously, we collected 24-h ventilator-derived VCO2, extracted the respiratory quotient of the administered nutrition, and calculated EE with a rewritten Weir formula. Bias, precision, and accuracy and inaccuracy rates were determined and compared with four predictive equations: the Harris-Benedict, Faisy, and Penn State University equations and the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline equation of 25 kcal/kg/day. RESULTS: Mean 24-h indirect calorimetry EE was 1823 ± 408 kcal. EE from ventilator-derived VCO2 was accurate (bias +141 ± 153 kcal/24 h; 7.7 % of gold standard) and more precise than the predictive equations (limits of agreement -166 to +447 kcal/24 h). The 10 % and 15 % accuracy rates were 61 % and 76 %, respectively, which were significantly higher than those of the Harris-Benedict, Faisy, and ESPEN guideline equations. Large errors of more than 30 % inaccuracy did not occur with EE derived from ventilator-derived VCO2. This 30 % inaccuracy rate was significantly lower than that of the predictive equations. CONCLUSIONS: In critically ill mechanically ventilated patients, assessment of EE based on ventilator-derived VCO2 is accurate and more precise than frequently used predictive equations. It allows for continuous monitoring and is the best alternative to indirect calorimetry.

Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.

INTRODUCTION: Higher body mass index (BMI) is associated with lower mortality in mechanically ventilated critically ill patients. However, it is yet unclear which body component is responsible for this relationship. METHODS: This retrospective analysis in 240 mechanically ventilated critically ill patients included adult patients in whom a computed tomography (CT) scan of the abdomen was made on clinical indication between 1 day before and 4 days after admission to the intensive care unit. CT scans were analyzed at the L3 level for skeletal muscle area, expressed as square centimeters. Cutoff values were defined by receiver operating characteristic (ROC) curve analysis: 110 cm2 for females and 170 cm2 for males. Backward stepwise regression analysis was used to evaluate low-muscle area in relation to hospital mortality, with low-muscle area, sex, BMI, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and diagnosis category as independent variables. RESULTS: This study included 240 patients, 94 female and 146 male patients. Mean age was 57 years; mean BMI, 25.6 kg/m2. Muscle area for females was significantly lower than that for males (102 ± 23 cm2 versus 158 ± 33 cm2; P < 0.001). Low-muscle area was observed in 63% of patients for both females and males. Mortality was 29%, significantly higher in females than in males (37% versus 23%; P = 0.028). Low-muscle area was associated with higher mortality compared with normal-muscle area in females (47.5% versus 20%; P = 0.008) and in males (32.3% versus 7.5%; P < 0.001). Independent predictive factors for mortality were low-muscle area, sex, and APACHE II score, whereas BMI and admission diagnosis were not. Odds ratio for low-muscle area was 4.3 (95% confidence interval, 2.0 to 9.0, P < 0.001). When applying sex-specific cutoffs to all patients, muscle mass appeared as primary predictor, not sex. CONCLUSIONS: Low skeletal muscle area, as assessed by CT scan during the early stage of critical illness, is a risk factor for mortality in mechanically ventilated critically ill patients, independent of sex and APACHE II score. Further analysis suggests muscle mass as primary predictor, not sex. BMI is not an independent predictor of mortality when muscle area is accounted for.

Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: a prospective observational cohort study.

BACKGROUND: Optimal nutrition for patients in the intensive care unit has been proposed to be the provision of energy as determined by indirect calorimetry and the provision of protein of at least 1.2 g/kg. METHODS: Prospective observational cohort study in a mixed medical-surgical intensive care unit in an academic hospital. In total, 886 consecutive mechanically ventilated patients were included. Nutrition was guided by indirect calorimetry and protein provision of at least 1.2 g/kg. Cumulative intakes were calculated for the period of mechanical ventilation. Cox regression was used to analyze the effect of protein + energy target achieved or energy target achieved versus neither target achieved on 28-day mortality, with adjustments for sex, age, body mass index, Acute Physiology and Chronic Health Evaluation II, diagnosis, and hyperglycemic index. RESULTS: Patients' mean age was 63 ± 16 years; body mass index, 26 ± 6; and Acute Physiology and Chronic Health Evaluation II, 23 ± 8. For neither target, energy target, and protein + energy target, energy intake was 75% ± 15%, 96% ± 5%, and 99% ± 5% of target, and protein intake was 72% ± 20%, 89% ± 10%, and 112% ± 12% of target, respectively. Hazard ratios (95% confidence interval) for energy target and protein + energy target were 0.83 (0.67-1.01) and 0.47 (0.31-0.73) for 28-day mortality. CONCLUSIONS: Optimal nutritional therapy in mechanically ventilated, critically ill patients, defined as protein and energy targets reached, is associated with a decrease in 28-day mortality by 50%, whereas only reaching energy targets is not associated with a reduction in mortality.