High protein versus medium protein delivery under equal total energy delivery in critical care: A randomized controlled trial

Nakamura, Kensuke; Nakano, Hidehiko; Naraba, Hiromu; Mochizuki, Masaki; Takahashi, Yūji; Sonoo, Tomohiro; Hashimoto, Hideki; Morimura, Naoto

doi:10.1016/j.clnu.2020.07.036

Cited by 69 publications

(108 citation statements)

References 37 publications

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“…Interestingly, subgroup analyses revealed that a highprotein supply was only effective when combined with active early rehabilitation. In consequence, the authors concluded that only a combination of 'high' protein supply and physical rehabilitation could help to preserve muscle mass in ICU patients [33]. However, since these studies focused on high protein supply in the early phase of critical illness, a comparison of the same to the results of the current study is limited.…”

Section: Discussionmentioning

confidence: 67%

“…Thus, conclusions concerning the effects of a high-protein protocol on muscle mass cannot be drawn. In contrast, Nakamura et al [33] conducted a randomized controlled trial (n ¼ 117) to assess the effect of high-protein (1.8 g/kg BW/d) compared to medium-protein supply (0.9 g/kg BW/d) under equal energy intake (target defined per kg BW/d; nutrition therapy initiated within 48 h after ICU admission) on the loss of femoral muscle volume without (n ¼ 56) and in combination with active early rehabilitation (belt-type electrical muscle stimulation; n ¼ 61). Concurrent to similar clinical trials, including ours, the protein supply did not reach the target (median of actual intake: 1.5 g and 0.8 g/kg BW/d, respectively).…”

Section: Discussionmentioning

confidence: 88%

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Medical high-protein nutrition therapy and loss of muscle mass in adult ICU patients: A randomized controlled trial

et al. 2021

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Background & aims: The degradation of muscle mass and loss of functional proteins due to catabolism are associated with adverse outcomes in critically ill patients. While an adequate supply of protein within a medical nutrition concept is suggested to minimize proteolysis, the specificities on appropriate dosage and timing are still under debate. The current study aimed to evaluate the effect of two different quantities of protein as part of a standardized energetically controlled nutrition therapy for the preservation of muscle mass in the later phase of critical illness. Methods: A randomized controlled trial was conducted in 42 critically ill patients (age 65 ± 15; 12 females; SAPS 45 ± 11; TISS 20 ± 7; SOFA-score 7 ± 3). The subjects were randomly assigned to either the intervention (1.8 g protein/kg body weight [BW]/d) or standard (1.2 g protein/kg BW/d) group. Nutrient supply via enteral and/or parenteral nutrition was calculated based on the individual energy expenditure measured by indirect calorimetry and target protein content. Quadriceps muscle layer thickness (QMLT) was observed through sonography at inclusion, and during the follow-up period, two and four weeks after inclusion. The measurement points were fixed on two sides at the midpoint and two-thirds between the anterior superior iliac spine and top of the patella. The data were analyzed descriptively wherein chi-squared tests or unpaired two-samle t-tests checked group differences. Daily changes in muscle mass were estimated using a linear mixed model. All data are shown as the mean ± standard deviation (SD). Results: Actual protein intake reached 1.5 ± 0.5 g and 1.0 ± 0.5 g/kg BW/d in the intervention and standard group, respectively. Mean values of all measurements of QMLT at inclusion (day 13 ± 2 after ICU admission) were 13.5 ± 7.4 mm and 13.4 ± 7.1 mm in the intervention and standard group, respectively (P ¼ 0.967). In both the groups, QMLT decreased over time (P < 0.001), while the estimated mean values of daily QMLT changes were À0.15 ± 0.08 mm (intervention) and À0.28 ± 0.08 mm (standard) without significant between-group differences (intervention effect, P ¼ 0.368; time x intervention effect, P ¼ 0.242). Illness scores and clinical outcomes showed no group differences. Conclusion: In this single-center trial the increased amounts of protein (1.5 g vs. 1.0 g/kg BW/d) provided through medical nutrition therapy in the late phase of critical illness did not achieve a statistically significant impact on the loss of muscle mass in long-term immobilized ICU patients. Larger multi-center trials are needed to evaluate whether observed numerical differences in muscle mass could be a true finding, and will translate into improved clinical outcomes. Trial registration: German Clinical Trials Register (http://www.drks.de/), DRKS-ID: DRKS00013594.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 88%

Medical high-protein nutrition therapy and loss of muscle mass in adult ICU patients: A randomized controlled trial

et al. 2021

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“…The systematic reviews by Davies and Fetterplace included studies that had significant differences in calories between groups, which may limit interpretation of results as the confounding effect of calories intake cannot be excluded [12,13]. Furthermore, since the publication of the last meta-analysis, several other RCTs have been published that were not included in these analyses [14,15].…”

Section: Introductionmentioning

confidence: 99%

The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials

et al. 2021

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Background The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients. Methods We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Results Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75–1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD −3.44% per week, 95% CI −4.99 to −1.90; p < 0.0001). Conclusion In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery. PROSPERO registration number: CRD42021237530

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“…Another strategy is to ensure sufficient protein intake during the acute phase. Nakamura et al reported that protein intake of 1.5 g/kg/day prevented muscle atrophy during the first 10 days of ICU admission, compared with 0.8 g/kg/day (12.9% ± 8.5% vs. 16.9% ± 7.0% in 1.5 vs. 0.8 g/kg/day, p < 0.01) [70]. These strategies in the acute phase will possibly prevent PICS.…”

Section: Picsmentioning

confidence: 99%

Urinary Titin N-fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

Nakanishi¹,

Tsutsumi²,

Hara³

et al. 2020

Preprint

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Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interplays the contraction of actin-containing thin filaments and myosin-containing thick filaments. The breakdown product of titin has been measurable in urine as urinary titin N-fragments. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome.

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High protein versus medium protein delivery under equal total energy delivery in critical care: A randomized controlled trial

Cited by 69 publications

References 37 publications

Medical high-protein nutrition therapy and loss of muscle mass in adult ICU patients: A randomized controlled trial

Medical high-protein nutrition therapy and loss of muscle mass in adult ICU patients: A randomized controlled trial

The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials

Urinary Titin N-fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

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