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.

Calculation of protein requirements; a comparison of calculations based on bodyweight and fat free mass.

BACKGROUND & AIMS: In dietary practice, it is common to estimate protein requirements on actual bodyweight, but corrected bodyweight (in cases with BMI <20 kg/m2 and BMI ≥30 kg/m2) and fat free mass (FFM) are also used. Large differences on individual level are noticed in protein requirements using these different approaches. To continue this discussion, the answer is sought in a large population to the following question: Will choosing actual bodyweight, corrected bodyweight or FFM to calculate protein requirements result in clinically relevant differences? METHODS: This retrospective database study, used data from healthy persons ≥55 years of age and in- and outpatients ≥18 years of age. FFM was measured by air displacement plethysmography technology or bioelectrical impedance analysis. Protein requirements were calculated as 1) 1.2 g (g) per kilogram (kg) actual bodyweight or 2) corrected bodyweight or 3) 1.5 g per kg FFM. To compare these three approaches, the approach in which protein requirement is based on FFM, was used as reference method. Bland-Altman plots with limits of agreement were used to determine differences, analyses were performed for both populations separately and stratified by BMI category and gender. RESULTS: In total 2291 subjects were included. In the population with relatively healthy persons (n = 506, ≥55 years of age) mean weight is 86.5 ± 18.2 kg, FFM is 51 ± 12 kg and in the population with adult in- and outpatients (n = 1785, ≥18 years of age) mean weight is 72.5 ± 18.4 kg, FFM is 51 ± 11 kg. Clinically relevant differences were found in protein requirement between actual bodyweight and FFM in most of the participants with overweight, obesity or severe obesity (78-100%). Using corrected bodyweight, an overestimation in 48-92% of the participants with underweight, healthy weight and overweight is found. Only in the Amsterdam UMC population, protein requirement is underestimated when using the approach of corrected bodyweight in participants with severe obesity. CONCLUSION: The three approaches in estimation of protein requirement show large differences. In the majority of the population protein requirement based on FFM is lower compared to actual or corrected bodyweight. Correction of bodyweight reduces the differences, but remain unacceptably large. It is yet unknown which method is the best for estimation of protein requirement. Since differences vary by gender due to differences in body composition, it seems more accurate to estimate protein requirement based on FFM. Therefore, we would like to advocate for more frequent measurement of FFM to determine protein requirements, especially when a deviating body composition is to be expected, for instance in elderly and persons with overweight, obesity or severe obesity.

Computed tomography reference values for visceral obesity and increased metabolic risk in a Caucasian cohort.

BACKGROUND: Visceral obesity is associated with the metabolic syndrome. The metabolic risk differs per ethnicity, but reference values for visceral obesity for body composition analyses using Computed Tomography (CT) scans in the Caucasian population are lacking. Therefore, the aim of this study was to define gender specific reference values for visceral obesity in a Caucasian cohort based upon the association between the amount of visceral adipose tissue (VAT) and markers of increased metabolic risk. METHODS: Visceral Adipose Tissue Area Index (VATI cm2/m2) at the level of vertebra L3 was analyzed using CT scans of 416 healthy living kidney donor candidates. The use of antihypertensive drugs and/or statins was used as an indicator for increased metabolic risk. Gender specific cut-off values for VATI with a sensitivity ≥80% were calculated using receiver operating characteristic (ROC) curves. RESULTS: In both men and women who used antihypertensive drugs, statins or both, VATI was higher than in those who did not use these drugs (p ≤ 0.013). In males and females respectively, a value of VATI of ≥38.7 cm2/m2 and ≥24.9 cm2/m2 was associated with increased metabolic risk with a sensitivity of 80%. ROC analysis showed that VATI was a better predictor of increased metabolic risk than BMI (area under ROC curve (AUC) = 0.702 vs AUC = 0.556 in males and AUC = 0.757 vs AUC = 0.630 in females). CONCLUSION: Gender and ethnicity specific cut-off values for visceral obesity are important in body composition research, although further validation is needed. This study also showed that quantification of VATI is a better predictor for metabolic risk than BMI.

State of the art: the role of citrulline as biomarker in patients with chemotherapy- or graft-versus-host-disease-induced mucositis.

PURPOSE OF REVIEW: Serum or plasma citrulline levels are used as biomarker for a broad spectrum of intestinal functions. During high-dose chemotherapy, citrulline levels are decreased due to mucositis, a common side effect of chemotherapy. This may decrease intestinal function and result in diarrhea. In this review, most recent studies investigating citrulline as biomarker for intestinal function are discussed, with focus on patients with oncological diseases, specifically hematological malignancies with chemotherapy- or Graft-versus-Host-disease (GVHD)-induced mucositis. RECENT FINDINGS: Citrulline has recently been widely studied in relation to intestinal function and various clinical conditions. It seems therefore a promising noninvasive biomarker in clinical practice for more than intestinal function alone. The association between citrulline levels and intestinal function in patients with hematological malignancies, with or without mucositis remains unclear, as no other parameters of intestinal function for this purpose were assessed. SUMMARY: In conclusion, citrulline seems to be a promising noninvasive biomarker for various intestinal conditions in general, and potentially for intestinal function in patients with chemotherapy- or GVHD-induced mucositis. It is unclear from recent literature whether high fecal volume or diarrhea as side effect, results in impaired intestinal function and severe malabsorption and if citrulline biomarkers can be useful to detect this.

Adherence to guidelines on nutrition support during intensive treatment of acute myeloid leukemia patients: A nationwide comparison.

BACKGROUND & AIMS: The level of adherence to the updated guidelines of The European Societies for Clinical Nutrition and Metabolism (ESPEN) and for Blood and Marrow Transplantation (EBMT) on nutrition in intensively treated adult acute myeloid leukemia (AML) patients in clinical practice is unknown. The aim of this nationwide survey was to investigate ESPEN/EBMT nutritional guideline adherence during intensive AML treatment, variation in nutrition support practices among hospitals and whether these practices changed after guideline publication. METHODS: All 22 Dutch hospitals providing (aftercare following) high-dose chemotherapy and/or hematopoietic stem cell transplantation for adult AML patients were surveyed on nutrition support practices during these intensive AML treatments. We used an online questionnaire in 2015 and semi-structured telephone interviews in 2018-2019. Both surveys were completed by registered dieticians and addressed the use of enteral (EN) and parenteral (PN) nutrition. The ESPEN/EBMT nutritional guideline adherence was investigated through the telephone interviews. RESULTS: High-level ESPEN/EBMT guideline adherence and/or uniformity among hospitals regarding nutrition support practices during intensive AML treatment were observed for nutritional screening, -aims, safe food handling and exercise training. Adherence to ESPEN/EBMT recommendations that were not implemented into national guidelines, including nutritional assessment and use of medical nutrition, was poor. All hospitals assessed nutritional intake, -impact symptoms and body weight, but muscle mass, physical performance and degree of systemic inflammation were rarely and variably monitored. Although the number of hospitals using EN as first-choice nutritional intervention increased from 3 hospitals in 2015 to 8 in 2019, PN remained the preferred method of nutrition support. Furthermore, the timing of medical nutrition varied. CONCLUSIONS: Although the use of EN increased after publication of the updated ESPEN/EBMT nutritional guidelines, adherence to these standards was limited and there was heterogeneity in nutrition support practices during intensive AML treatment among hospitals. Incorporating international nutritional standards into national guidelines by nutrition expert groups immediately upon publication may improve adherence.

Validity of the "Rate-a-Plate" Method to Estimate Energy and Protein Intake in Acutely Ill, Hospitalized Patients.

BACKGROUND: Prevalence of malnutrition in hospitals has been reported around 20% and increases during hospitalization. The "Rate-a-Plate" method has been developed to monitor dietary intake and identify patients whose nutrition status deteriorates during hospitalization, but has not yet been validated. The objective was to study the validity and reliability of the method (phase 1) and redesign and revalidate a revised version (phase 2). METHODS: Detailed food records provided a reference method. A priori difference of >20% in energy or protein between the reference and the "Rate-a-Plate" method was determined as clinically relevant. Intraclass correlation coefficients were used to determine the reliability. RESULTS: In phase 1, 24 patients were included with a total 67 test days. In phase 2, 14 patients were included, 28 test days. In phase 1, the "Rate-a-Plate" method underestimated intake by 422 kcal (29%, ICC 0.349, 95% CI 304-541) and 5.7 g protein (10%, ICC 0.511, 95% CI 0.0-11.5). Underestimation was found in 65% and 23% for energy and protein intake, respectively. Underestimation was higher when patients had higher intake. In phase 2, underestimation was 109 kcal (7%, ICC 0.788, 95% CI -273 to 56) and 3.7 g protein (6%, ICC 0.905, 95% CI -8.4 to 1.0). In 32% and 21% of the cases, energy and protein intake were underestimated. CONCLUSION: The revised version of the "Rate-a-Plate" method is a valid method to monitor energy and protein intake of hospitalized patients and can be filled out by nutrition assistants. A larger validation study is required.

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).

Early high protein intake and mortality in critically ill ICU patients with low skeletal muscle area and -density.

BACKGROUND & AIMS: Optimal nutritional support during the acute phase of critical illness remains controversial. We hypothesized that patients with low skeletal muscle area and -density may specifically benefit from early high protein intake. Aim of the present study was to determine the association between early protein intake (day 2-4) and mortality in critically ill intensive care unit (ICU) patients with normal skeletal muscle area, low skeletal muscle area, or combined low skeletal muscle area and -density. METHODS: Retrospective database study in mechanically ventilated, adult critically ill patients with an abdominal CT-scan suitable for skeletal muscle assessment around ICU admission, admitted from January 2004 to January 2016 (n = 739). Patients received protocolized nutrition with protein target 1.2-1.5 g/kg/day. Skeletal muscle area and -density were assessed on abdominal CT-scans at the 3rd lumbar vertebra level using previously defined cut-offs. RESULTS: Of 739 included patients (mean age 58 years, 483 male (65%), APACHE II score 23), 294 (40%) were admitted with normal skeletal muscle area and 445 (60%) with low skeletal muscle area. Two hundred (45% of the low skeletal muscle area group) had combined low skeletal muscle area and -density. In the normal skeletal muscle area group, no significant associations were found. In the low skeletal muscle area group, higher early protein intake was associated with lower 60-day mortality (adjusted hazard ratio (HR) per 0.1 g/kg/day 0.82, 95%CI 0.73-0.94) and lower 6-month mortality (HR 0.88, 95%CI 0.79-0.98). Similar associations were found in the combined low skeletal muscle area and -density subgroup (HR 0.76, 95%CI 0.64-0.90 for 60-day mortality and HR 0.80, 95%CI 0.68-0.93 for 6-month mortality). CONCLUSIONS: Early high protein intake is associated with lower mortality in critically ill patients with low skeletal muscle area and -density, but not in patients with normal skeletal muscle area on admission. These findings may be a further step to personalized nutrition, although randomized studies are needed to assess causality.

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 analyses: agreement between non-contrast and contrast CT scan measurements of skeletal muscle area and mean muscle attenuation.

Low skeletal muscle area (SMA) and muscle radiation attenuation (MRA) have been associated with poor prognosis in various patient populations. Both non-contrast and contrast CT scans are used to determine SMA and MRA. The effect of the use of a contrast agent on SMA and MRA is unknown. Therefore, we investigated agreement between these two scan options. SMA and MRA of 41 healthy individuals were analysed on a paired non-contrast and contrast single CT scan, and agreement between paired scan results was assessed with use of Bland-Altman plots, intraclass correlation coefficients (ICCs), standard error of measurements (SEM) and smallest detectable differences at a 95% confidence level (SDD95 ). Analyses were stratified by tube voltage. Difference in SMA between non-contrast and contrast scans made with a different tube voltage was 7·0 ± 7·5 cm2 ; for scans made with the same tube voltage this was 2·3 ± 1·7 cm2 . Agreement was excellent for both methods: ICC: 0·952, SEM: 7·2 cm2 , SDD95 : 19·9 cm2 and ICC: 0·997, SEM: 2·0 cm2 , SDD95 : 5·6 cm2 , respectively. MRA of scans made with a different tube voltage differed 1·3 ± 11·3 HU, and agreement was poor (ICC: 0·207, SEM: 7·9 HU, SDD95 : 21·8 HU). For scans made with the same tube voltage the difference was 6·7 ± 3·2 HU, and agreement was good (ICC: 0·682, SEM: 5·3 HU, SDD95 : 14·6 HU). In conclusion, SMA and MRA can be slightly influenced by the use of contrast agent. To minimise measurement error, image acquisition parameters of the scans should be similar.

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 .

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.