RESUMEN
BACKGROUND: Amino acid availability is a regulatory factor of protein anabolism and is partly dependent on enteral amino acid uptake. During continuous enteral feeding, enteral amino acid uptake may vary considerably, but this has not been documented systematically. METHODS: In this pragmatic study, we investigated patients in the intensive care unit (n = 10) and healthy adults (n = 10). The time course of essential amino acid concentrations in arterial plasma and the uptake of dietary phenylalanine were recorded during 12 hours of continuous enteral feeding, using a 13C-labeled phenylalanine tracer. RESULTS: Plasma essential amino acid concentrations and 13C-phenylalanine enrichment reached a tentative steady state after no more than 4.5 h from start of tracer infusion. There was a large intra- and inter-individual variability in both cohorts. No periodicity could be detected in the temporal variation. CONCLUSION: During continuous enteral feeding, uptake of amino acids shows large intra- and inter-individual variation. A tentative steady state of 13C-phenylalanine uptake is eventually reached. TRIAL REGISTRATION: Registered at Australian New Zealand Clinical Trials Registry, trial ID ACTRN12616000593437.
Asunto(s)
Aminoácidos Esenciales/farmacocinética , Proteínas en la Dieta/farmacocinética , Nutrición Enteral , Fenilalanina/farmacocinética , Adulto , Anciano , Aminoácidos Esenciales/sangre , Disponibilidad Biológica , Estudios de Casos y Controles , Enfermedad Crítica , Proteínas en la Dieta/sangre , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Periodicidad , Fenilalanina/sangre , Trazadores Radiactivos , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Timing, dose, and route of protein feeding in critically ill patients treated in an ICU is controversial. This is because of conflicting outcomes observed in randomized controlled trials (RCTs). This inconsistency between RCTs may occur as the physiology of protein metabolism and protein handling in the critically ill is substantially different from the healthy with limited mechanistic data to inform design of RCTs. This review will outline the current knowledge and gaps in the understanding of protein absorption and kinetics during critical illness. RECENT FINDINGS: Critically ill patients, both children and adults, lose muscle protein because of substantial increases in protein degradation with initially normal, and over time increasing, protein synthesis rates. Critically ill patients appear to retain the capacity to absorb dietary protein and to use it for building body protein; however, the extent and possible benefit of this needs to be elucidated. More sophisticated methods to study protein absorption and digestion have recently been described but these have yet to be used in the critically ill. SUMMARY: Adequate understanding of protein absorption and kinetics during critical illness will help the design of better interventional studies in the future. Because of the complexity of measuring protein absorption and kinetics in the critically ill, very few investigations are executed. Recent data using isotope-labelled amino acids suggests that critically ill patients are able to absorb enteral protein and to synthesize new body protein. However, the magnitude of absorption and anabolism that occurs, and possible benefits for the patients need to be elucidated.
Asunto(s)
Enfermedad Crítica , Proteínas en la Dieta , Adulto , Niño , Humanos , Cinética , ProteolisisRESUMEN
BACKGROUND: Enteral nutrition (EN) is a ubiquitous intervention in ICU patients but there is uncertainty regarding the optimal dose, timing and importance for patient-centered outcomes during critical illness. Our research group has previously found an improved protein balance during normocaloric versus hypocaloric parenteral nutrition in neurosurgical ICU patients. We now wanted to investigate if this could be demonstrated in a general ICU population with established enteral feeding, including patients on renal replacement therapy. METHODS: Patients with EN >80% of energy target as determined by indirect calorimetry were randomized to or 50% or 100% of current EN rate. After 24 hours, whole-body protein kinetics were determined by enteral and parenteral stable isotope tracer infusions. Treatment allocation was then switched, and tracer investigations repeated 24 hours later in a crossover design with patients serving as their own controls. RESULTS: Six patients completed the full protocol. During feeding with 100% EN all patients received >1.2 g/kg/day of protein. Mean whole-body protein balance increased from -6.07 to 2.93 µmol phenylalanine/kg/h during 100% EN as compared to 50% (p = 0.044). The oxidation rate of phenylalanine was unaltered (p = 0.78). CONCLUSIONS: It is possible to assess whole-body protein turnover using a stable isotope technique in critically ill patients during enteral feeding and renal replacement therapy. Our results also suggest a better whole-body protein balance during full dose as compared to half dose EN. As the sample size was smaller than anticipated, this finding should be confirmed in larger studies.
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Metabolismo Energético , Nutrición Enteral/métodos , Proteínas/metabolismo , Adulto , Anciano , Isótopos de Carbono/química , Enfermedad Crítica , Estudios Cruzados , Ingestión de Energía , Femenino , Humanos , Unidades de Cuidados Intensivos , Marcaje Isotópico , Cinética , Masculino , Persona de Mediana Edad , Nutrición Parenteral , Fenilalanina/química , Fenilalanina/metabolismo , Recuento Corporal Total/métodosRESUMEN
BACKGROUND: Providing supplemental amino acids to ICU patients during a 3-h period results in improved whole-body net protein balance, without an increase in amino acid oxidation. The primary objective was to investigate if a 24-h intravenous amino acid infusion in critically ill patients has a sustained effect on whole-body protein balance as was seen after 3 h. Secondary objectives were monitoring of amino acid oxidation rate, urea and free amino acid plasma concentrations. METHODS: An infusion of [1-13C]-phenylalanine was added to ongoing enteral nutrition to quantify the enteral uptake of amino acids. Primed intravenous infusions of [ring-2H5]-phenylalanine and [3,3-2H2]-tyrosine were used to assess whole-body protein synthesis and breakdown, to calculate net protein balance and to assess amino acid oxidation at baseline and at 3 and 24 hours. An intravenous amino acid infusion was added to nutrition at a rate of 1 g/kg/day and continued for 24 h. RESULTS: Eight patients were studied. The amino acid infusion resulted in improved net protein balance over time, from -1.6 ± 7.9 µmol phe/kg/h at 0 h to 6.0 ± 8.8 at 3 h and 7.5 ± 5.1 at 24 h (p = 0.0016). The sum of free amino acids in plasma increased from 3.1 ± 0.6 mmol/L at 0 h to 3.2 ± 0.3 at 3 h and 3.6 ± 0.5 at 24 h (p = 0.038). Amino acid oxidation and plasma urea were not altered significantly. CONCLUSION: We demonstrated that the improvement in whole-body net protein balance from a supplemental intravenous amino acid infusion seen after 3 h was sustained after 24 h in critically ill patients. TRIAL REGISTRATION: This trial was prospectively registered at Australian New Zealand Clinical Trials Registry. ACTRN, 12615001314516 . Registered on 1 December 2015.
Asunto(s)
Aminoácidos/farmacología , Proteínas/efectos de los fármacos , Proteínas/metabolismo , Anciano , Aminoácidos/uso terapéutico , Análisis de Varianza , Enfermedad Crítica/terapia , Nutrición Enteral/métodos , Femenino , Humanos , Infusiones Intravenosas/métodos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Fenómenos Fisiológicos de la Nutrición/efectos de los fármacos , Oxidación-Reducción , Fenilalanina/análisis , Fenilalanina/sangre , Estadísticas no ParamétricasRESUMEN
The high fashion in nutrition for the critically ill is to recommend a high protein intake. Several opinion leaders are surfing on this wave, expanding the suggested protein allowance upwards. At the same time, there is no new evidence supporting this change in recommendations. Observational data show that in clinical practice protein intake is most often far below current ESPEN recommendations of 1.2-1.5 g/kg/day. Therefore, it may be in the best interests of our patients just to adhere to that guideline, and not to stretch them upwards for protein intake? Here we give arguments to stay conservative.
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Enfermedad Crítica/terapia , Proteínas en la Dieta/efectos adversos , Proteínas en la Dieta/uso terapéutico , Encuestas Nutricionales/normas , Humanos , Nitrógeno/metabolismo , Encuestas Nutricionales/métodosRESUMEN
PURPOSE OF REVIEW: Muscle wasting is dramatic in critically ill patients and related to worsened outcome. The question is whether this can be prevented or reduced by adequate protein feeding. Recommendations for protein requirements are different between different societies, because of limited and weak evidence. Most studies, on which these recommendations are based, use nitrogen balance as primary outcome. However, nitrogen balance to estimate protein needs over short periods, is not reliable. RECENT FINDINGS: Studies using tracer methodology to assess the effects of feeding on whole-body protein synthesis, breakdown and balance, show that both adult and pediatric critically ill patients can utilize parenterally and enterally given proteins or amino acids to build body protein, and that the extra amino acids are not oxidized. SUMMARY: Recent studies show a positive correlation between protein intake and protein balance, with many patients reaching a positive protein balance. However, many questions remain. Especially whether adult patients should have a constant positive protein balance, whether the route of administration affects utilization, which proteins are synthesized and whether these are beneficial, is more protein better and what is the upper limit, and whether a positive protein balance affects clinical outcome?
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Enfermedad Crítica/terapia , Proteínas en la Dieta/administración & dosificación , Unidades de Cuidados Intensivos , Apoyo Nutricional/métodos , Desnutrición Proteico-Calórica/prevención & control , Aminoácidos/administración & dosificación , Proteínas en la Dieta/sangre , Ingestión de Energía , Humanos , Biosíntesis de Proteínas/fisiologíaRESUMEN
INTRODUCTION: Evidence behind the recommendations for protein feeding during critical illness is weak. Mechanistic studies are needed to elucidate the effects of amino acid and/or protein supplementation on protein metabolism before larger clinical trials with higher levels of protein feeding are initiated. METHODS: We studied the effects of parenteral amino acid supplementation (equivalent to 1 g/kg/day) over the course of 3 hours on whole-body protein turnover in critically ill patients in the intensive care unit (ICU) during the first week after admission. Patients were studied at baseline during ongoing nutrition and during extra amino acid supplementation. If the patient was still in the ICU 2 to 4 days later, these measurements were repeated. Protein kinetics were measured using continuous stable isotope-labeled phenylalanine and tyrosine infusions. RESULTS: Thirteen patients were studied on the first study occasion only, and seven were studied twice. Parenteral amino acid supplementation significantly improved protein balance on both occasions, from a median of -4 to +7 µmol phenylalanine/kg/hr (P =0.001) on the first study day and from a median of 0 to +12 µmol phenylalanine/kg/hr (P =0.018) on the second study day. The more positive protein balance was attributed to an increased protein synthesis rate, which reached statistical significance during the first measurement (from 58 to 65 µmol phenylalanine/kg/hr; n =13; P =0.007), but not during the second measurement (from 58 to 69 µmol phenylalanine/kg/hr; n =7; P =0.09). Amino acid oxidation rates, estimated by phenylalanine hydroxylation, did not increase during the 3-hour amino acid infusion. A positive correlation (r =0.80; P <0.0001) was observed between total amino acids and/or protein given to the patient and whole-body protein balance. CONCLUSION: Extra parenteral amino acids infused over a 3-hour period improved whole-body protein balance and did not increase amino acid oxidation rates in critically ill patients during the early phase (first week) of critical illness.
Asunto(s)
Enfermedad Crítica/terapia , Fenilalanina/administración & dosificación , Proteínas/metabolismo , Aminoácidos/sangre , Nutrición Enteral , Femenino , Humanos , Infusiones Parenterales , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
BACKGROUND: Critically ill patients are susceptible to protein catabolism. Enteral feeding may ameliorate protein loss, but its effect is not well characterized in terms of protein kinetics. OBJECTIVE: We established a method of quantifying the effect of enteral protein feeding on whole-body protein turnover and studied critically ill patients receiving early enteral nutrition. DESIGN: In a proof-of-concept study, we established, in healthy subjects (n = 6), a method of measuring the effect of continuous enteral protein feeding on whole-body protein turnover by using ¹³C-phenylalanine (¹³C-Phe) intrinsically labeled casein by a nasogastric feeding tube and an intravenous ²H5-Phe tracer. The protocol was applied to study critically ill patients (n = 10) during the initial hypocaloric-hyponitrogenous dose of enteral nutrition. RESULTS: Patients were catabolic with a negative protein balance. The median splanchnic extraction fraction of hourly dietary Phe intake was 92% (range: 86-99%); that is, the availability of dietary Phe in arterial plasma was low. In patients with a stable parenteral amino acid supply (n = 7), the median net protein balance improved during enteral feeding from -8.6 to -5.8 µmol · kg body weight⻹ · h⻹ (P = 0.018). CONCLUSIONS: Whole-body protein turnover and the contribution of dietary protein can be quantified in critically ill patients by using intravenous and enteral stable-isotope Phe tracers. The whole-body protein balance improved during early hypocaloric-hyponitrogenous enteral protein feeding in these patients.
Asunto(s)
Restricción Calórica/efectos adversos , Enfermedad Crítica , Dieta con Restricción de Proteínas/efectos adversos , Metabolismo Energético , Nutrición Enteral/efectos adversos , Biosíntesis de Proteínas , Proteolisis , Anciano , Isótopos de Carbono , Estudios de Cohortes , Deuterio , Estudios de Factibilidad , Femenino , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Cinética , Masculino , Estabilidad Proteica , SueciaRESUMEN
BACKGROUND & AIMS: Upper-body, i.e. visceral, obesity is associated with insulin resistance and impaired protein synthesis. It is unclear whether postprandial stimulation of protein synthesis is affected by body fat distribution. We investigated the postprandial protein anabolic response in a cohort of obese women. METHODS: Participants were studied after an overnight fast and after a mixed meal, grouped as upper-body obese (UBO, waist-to-hip ratio, WHR, >0.85, n = 6) vs. lower-body obese (LBO, WHR <0.80, n = 7). Lipid and carbohydrate metabolism were assessed by measurements of plasma free fatty acids (FFA), insulin and glucose plasma concentrations, and calculation of the Quicki index from fasting glucose and insulin values. Different labels of stable isotopes of phenylalanine were administered intravenously and orally, and leg and whole-body protein breakdown and synthesis were calculated from phenylalanine/tyrosine isotopic enrichments in femoral arterial and venous blood, using equations for steady-state kinetics. Data are denoted as mean ± SD. RESULTS: Age (38 vs. 40, p = 0.549) and body-mass index (33.7 ± 1.9 vs. 35.0 ± 1.8, p = 0.241) were similar in both groups. UBO subjects had more visceral fat (p = 0.002) and higher fat-free body mass (FFM) (p = 0.015). Plasma insulin concentrations were greater in UBO than LBO women (p = 0.013), and UBO were less insulin sensitive (Quicki = 0.32 ± 0.01 vs. 0.36 ± 0.02, p = 0.005). Protein kinetics across the leg were not different between groups. Fasting whole body protein balance was similarly negative in both groups (UBO -6.5 ± 2.4 vs. LBO -7.6 ± 0.9 µmol/kgFFM/h, p = 1.0). Postprandially, whole body protein balance became less positive in UBO than in LBO (14.8 ± 3.7 vs. 20.2 ± 3.7 µmol/kgFFM/h, p = 0.017). CONCLUSIONS: Whole-body protein balance following a meal is less positive in upper-body obese, insulin-resistant, women than in lower-body obese women.