Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients - A protocol for the prospective randomised controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study

Abstract Background Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30-60 min period), while having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks. To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study (Protein Bolus Nutrition) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 hours) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis. Methods Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 hours after ICU admission. The primary outcome measure is the time until the daily protein target (≥1.5 g protein/kg bodyweight/24h) is achieved. Secondary outcome measures include tolerance of enteral feeding and evolution of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed. Discussion The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting. Trial registration ClinicalTrials.gov Identifier: NCT03587870, registered July 16, 2018. Swiss National Clinical Trial Portal identifier: SNCTP000003234, last updated July 24, 2019.

Download Full-text

Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients - A protocol for the prospective randomised controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study

10.21203/rs.2.23374/v3 ◽

2020 ◽

Author(s):

Simona Reinhold ◽

Désirée Yeginsoy ◽

Alexa Hollinger ◽

Atanas Todorov ◽

Lionel Tintignac ◽

...

Keyword(s):

Protein Synthesis ◽

Critically Ill ◽

Enteral Feeding ◽

Critically Ill Patients ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Secondary Outcome ◽

Pro Bono ◽

Randomised Controlled

Abstract Background Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30-60 min period), while having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks. To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study (Protein Bolus Nutrition) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 hours) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis.Methods Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 hours after ICU admission. The primary outcome measure is the time until the daily protein target (≥1.5 g protein/kg bodyweight/24h) is achieved. Secondary outcome measures include tolerance of enteral feeding and evolution of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed.Discussion The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting.Trial registration ClinicalTrials.gov Identifier: NCT03587870, registered July 16, 2018. Swiss National Clinical Trial Portal identifier: SNCTP000003234, last updated July 24, 2019.

Download Full-text

Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients - A protocol for the prospective randomised controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study

10.21203/rs.2.23374/v1 ◽

2020 ◽

Author(s):

Simona Reinhold ◽

Désirée Yeginsoy ◽

Alexa Hollinger ◽

Atanas Todorov ◽

Lionel Tintignac ◽

...

Keyword(s):

Protein Synthesis ◽

Critically Ill ◽

Enteral Feeding ◽

Critically Ill Patients ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Secondary Outcome ◽

Pro Bono ◽

Randomised Controlled

Abstract Background Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30-60 min period), while having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks. To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study ( Pro tein Bo lus N utriti o n) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 hours) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis. Methods Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 hours after ICU admission. The primary outcome measure is the time until the daily protein target (≥1.5 g protein/kg bodyweight/24h) is achieved. Secondary outcome measures include tolerance of enteral feeding and trajectory of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed. Discussion The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting.

Download Full-text

Intermittent feeding in intensive care – the theory and practice

10.33699/pis.2021.100.2.66-73 ◽

2021 ◽

Vol 100 (2) ◽

Keyword(s):

Intensive Care ◽

Critically Ill ◽

Enteral Feeding ◽

Critically Ill Patients ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Abdominal Discomfort ◽

Residual Volume ◽

Gastric Residual Volume ◽

Intermittent Feeding

Introduction: Nutrition therapy becomes one of the fundamental conditions of a successful outcome in malnourished patients and in critically ill patients. The administration of enteral feeding in critically ill patients is mostly performed by continuous or cyclic feeding. On the contrary, the potential benefits of intermittent feeding include increased muscle protein synthesis. This review outlines the theory of a possible anabolic effect of intermittent feeding. The authors describe their experience with implementation of this method of administration in the intensive care unit including the follow-up of possible complications and adverse effects. Methods: Six patients with intermittent feeding were followed retrospectively during the study period. In addition to demographic data, potential complications related to intermittent enteral feeding (aspiration pneumonia, increased gastric residual volume, abdominal discomfort, osmotic diarrhoea) were evaluated. Results: The average time of intermittent feeding was 8 days. The sum of intermittent feeding days was 63. No aspiration followed by pneumonia was detected during this period. The gastric residual volume did not increase, either. Abdominal discomfort and osmotic diarrhoea were not observed in any patient. Conclusion: Although continuous and cyclic enteral feeding in critically ill patients remains the standard and the most common practice, it is considered as a non-physiological method with possible negative consequences for the patient. On the other hand, intermittent feeding is theoretically associated with respecting of the circadian rhythm and with activation of autophagy. Intermittent feeding increases muscle protein synthesis and supports the release of fatty acids. As shown by our observational study, intermittent administration of enteral nutrition in intensive care can be implemented without any adverse effects; however, it is more time consuming for the nurses.

Download Full-text

Leucine-stimulated mTOR signaling is partly attenuated in skeletal muscle of chronically uremic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00068.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. E873-E881 ◽

Cited By ~ 16

Author(s):

Yu Chen ◽

Sumita Sood ◽

Kevin McIntire ◽

Richard Roth ◽

Ralph Rabkin

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Signaling Pathway ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Exercise Induced ◽

Rps6 Phosphorylation

The branched-chain amino acid leucine stimulates muscle protein synthesis in part by directly activating the mTOR signaling pathway. Furthermore, leucine, if given in conjunction with resistance exercise, enhances the exercise-induced mTOR signaling and protein synthesis. Here we tested whether leucine can activate the mTOR anabolic signaling pathway in uremia and whether it can enhance work overload (WO)-induced signaling through this pathway. Chronic kidney disease (CKD) and control rats were studied after 7 days of surgically induced unilateral plantaris muscle WO and a single leucine or saline load. In the basal state, 4E-BP1 phosphorylation was modestly depressed in non-WO muscle of CKD rats, whereas rpS6 phosphorylation was nearly completely suppressed. After oral leucine mTOR, S6K1 and rpS6 phosphorylation increased similarly in both groups, whereas the phospho-4E-BP1 response was modestly attenuated in CKD. WO alone activated the mTOR signaling pathway in control and CKD rats. In WO CKD, muscle leucine augmented mTOR and 4E-BP1 phosphorylation, but its effect on S6K1 phosphorylation was attenuated. Taken together, this study has established that the chronic uremic state impairs basal signaling through the mTOR anabolic pathway, an abnormality that may contribute to muscle wasting. However, despite this abnormality, leucine can stimulate this signaling pathway in CKD, although its effectiveness is partially attenuated, including in skeletal muscle undergoing sustained WO. Thus, although there is some resistance to leucine in CKD, the data suggest a potential role for leucine-rich supplements in the management of uremic muscle wasting.

Download Full-text

Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis

Clinical Science ◽

10.1042/cs20110233 ◽

2011 ◽

Vol 122 (3) ◽

pp. 133-142 ◽

Cited By ~ 82

Author(s):

Maria Klaude ◽

Maiko Mori ◽

Inga Tjäder ◽

Thomas Gustafsson ◽

Jan Wernerman ◽

...

Keyword(s):

Gene Expression ◽

Protein Degradation ◽

Critically Ill ◽

Critically Ill Patients ◽

Proteolytic Enzyme ◽

Muscle Wasting ◽

Muscle Protein ◽

Synthesis Rate ◽

Normal Muscle ◽

Enzyme Systems

Muscle wasting negatively affects morbidity and mortality in critically ill patients. This progressive wasting is accompanied by, in general, a normal muscle PS (protein synthesis) rate. In the present study, we investigated whether muscle protein degradation is increased in critically ill patients with sepsis and which proteolytic enzyme systems are involved in this degradation. Eight patients and seven healthy volunteers were studied. In vivo muscle protein kinetics was measured using arteriovenous balance techniques with stable isotope tracers. The activities of the major proteolytic enzyme systems were analysed in combination with mRNA expression of genes related to these proteolytic systems. Results show that critically ill patients with sepsis have a variable but normal muscle PS rate, whereas protein degradation rates are dramatically increased (up to 160%). Of the major proteolytic enzyme systems both the proteasome and the lysosomal systems had higher activities in the patients, whereas calpain and caspase activities were not changed. Gene expression of several genes related to the proteasome system was increased in the patients. mRNA levels of the two main lysosomal enzymes (cathepsin B and L) were not changed but, conversely, genes related to calpain and caspase had a higher expression in the muscles of the patients. In conclusion, the dramatic muscle wasting seen in critically ill patients with sepsis is due to increased protein degradation. This is facilitated by increased activities of both the proteasome and lysosomal proteolytic systems.

Download Full-text

Effect of heart failure on the regulation of skeletal muscle protein synthesis, breakdown, and apoptosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00517.2002 ◽

2003 ◽

Vol 284 (5) ◽

pp. E1001-E1008 ◽

Cited By ~ 15

Author(s):

Rebecca Persinger ◽

Yvonne Janssen-Heininger ◽

Simon S. Wing ◽

Dwight E. Matthews ◽

Martin M. LeWinter ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Protein Synthesis ◽

Food Intake ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Protein Synthesis

Heart failure is often characterized by skeletal muscle atrophy. The mechanisms underlying muscle wasting, however, are not fully understood. We studied 30 Dahl salt-sensitive rats (10 male, 20 female) fed either a high-salt (HS; n = 15) or a low-salt (LS; n = 15) diet. This strain develops cardiac hypertrophy and failure when fed a HS diet. LS controls were matched to HS rats for gender and duration of diet. Body mass, food intake, and muscle mass and composition were measured. Skeletal muscle protein synthesis was measured by isotope dilution. An additional group of 27 rats (HS, n = 16; LS; n = 11) were assessed for expression of genes regulating protein breakdown and apoptosis. Gastrocnemius and plantaris muscles weighed less (16 and 22%, respectively) in HS than in LS rats ( P < 0.01). No differences in soleus or tibialis anterior weights were found. Differences in muscle mass were abolished after data were expressed relative to body size, because HS rats tended ( P = 0.094) to weigh less. Lower body mass in HS rats was related to a 16% reduction ( P < 0.01) in food intake. No differences in muscle protein or DNA content, the protein-to-DNA ratio, or muscle protein synthesis were found. Finally, no differences in skeletal muscle gene expression were found to suggest increased protein breakdown or apoptosis in HS rats. Our results suggest that muscle wasting in this model of heart failure is not associated with alterations in skeletal muscle metabolism. Instead, muscle atrophy was related to reduced body weight secondary to decreased food intake. These findings argue against the notion that heart failure is characterized by a skeletal muscle myopathy that predisposes to atrophy.

Download Full-text

Muscle wasting in emphysema

Clinical Science ◽

10.1042/cs0750415 ◽

1988 ◽

Vol 75 (4) ◽

pp. 415-420 ◽

Cited By ~ 73

Author(s):

W. L. Morrison ◽

J. N. A. Gibson ◽

C. Scrimgeour ◽

M. J. Rennie

Keyword(s):

Protein Synthesis ◽

Protein Turnover ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Myofibrillar Protein ◽

Whole Body ◽

Protein Breakdown ◽

Body Protein ◽

Net Protein

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

Download Full-text

Depressed Muscle Protein Synthesis is the Predominant Mechanism of Muscle Wasting in Emphysema

Clinical Science ◽

10.1042/cs070063pa ◽

1986 ◽

Vol 70 (s13) ◽

pp. 63P-63P

Author(s):

W.L. Morrison ◽

J.N.A. Gibson ◽

R.N. Johnston ◽

R.A. Clark ◽

M.J. Rennie

Keyword(s):

Protein Synthesis ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis

Download Full-text

Resistance exercise and nutrition to counteract muscle wasting

Applied Physiology Nutrition and Metabolism ◽

10.1139/h09-093 ◽

2009 ◽

Vol 34 (5) ◽

pp. 817-828 ◽

Cited By ~ 49

Author(s):

Jonathan P. Little ◽

Stuart M. Phillips

Keyword(s):

Protein Synthesis ◽

Resistance Exercise ◽

Muscle Mass ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Effective Means ◽

Resistance Exercise Training ◽

Highly Effective

Loss of muscle mass is an unfavourable consequence of aging and many chronic diseases. The debilitating effects of muscle loss include declines in physical function and quality of life and increases in morbidity and mortality. Loss of muscle mass is the result of a decrease in muscle protein synthesis, an increase in muscle protein degradation, or a combination of both. Much research on muscle wasting has tended to focus on preventing muscle protein breakdown, and less attention has been paid to providing adequate stimulation to increase muscle protein synthesis. In this review, we present evidence to suggest that interventions aimed at increasing muscle protein synthesis represent the most effective countermeasure for preventing, delaying, or reversing the loss of skeletal muscle mass experienced in various muscle wasting conditions. Based on results from acute and chronic studies in humans in a wide variety of wasting conditions, we propose that resistance exercise training combined with appropriately timed protein (likely leucine-rich) ingestion represents a highly effective means to promote muscle hypertrophy, and may represent a highly effective treatment strategy to counteract the muscle wasting tassociated with aging and chronic disease.

Download Full-text