Energy expenditure and substrate utilization during critical illness

Background Critical illness leads to major alterations in metabolism. The net result is a state where catabolism predominates over anabolism. The associated loss of lean body mass is significant and potentially harmful. It is commonly held that providing calories and protein from nutrition may attenuate this response. Despite significant research efforts, an optimal dose for these therapies remains to be defined. The metabolic rate of ICU patients is readily measured by indirect calorimetry. Questions regarding the accuracy of modern instruments in the setting of mechanical ventilation have been an impediment to wider application of this technique. The physiological effects of common nutritional interventions on protein balance are difficult to assess in clinical practice but can be quantified using stable isotope tracers. Aims The studies of this thesis had two main aims: to validate techniques for gas exchange measurements in ICU, and to describe the effects of energy and/or amino acid supplementation on protein kinetics. In studies I and II we evaluated the measurement properties of three new instruments for indirect calorimetry in mechanically ventilated ICU patients against a clinical gold standard (Deltatrac). Study III investigated the effects of a supplemental amino acid infusion on whole-body protein balance in critically ill patients. In study IV, we quantified whole-body protein kinetics after 24 hours of full-dose or half-dose enteral nutrition in a randomized cross-over study design. Results In study I, we performed 48 measurements with the evaluated instruments and reference method in sequence. Mean resting energy expenditure (REE) was similar between Quark RMR and Deltatrac (p = 0.17). Mean REE from CCM Express was 64% higher than Deltatrac (p <0.001). In study II we conducted 48 simultaneous measurements with the evaluated instruments and Deltatrac. Compared to Deltatrac, both Quark RMR and E-sCOVX overestimated REE with similar bias and 95% limits of agreement. In study III, a 24-hour intravenous amino acid infusion resulted in a positive protein balance during the study period (p = 0.0016) without increasing amino acid oxidation (p = 0.147). In study IV, whole-body protein kinetics could be determined in six patients during half-dose and full-dose enteral nutrition. An improvement in protein balance was observed during full-dose nutrition (p = 0.044). Conclusions Measured energy expenditure is variable between instruments for indirect calorimetry. Apart from one device, agreement compared to the reference method was better than what is commonly accepted for other monitoring technologies in critical care. The studies of protein kinetics indicate that an increase in energy or amino acid delivery improves whole-body protein balance in critically ill patients. Indirect calorimetry and tracer techniques are promising methods to further our understanding of alterations in energy metabolism and substrate utilization during critical illness. In turn, this knowledge may assist in the development of clinical trials with patient-centered outcomes

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Effects of normocaloric vs. hypocaloric enteral nutrition on whole-body protein turnover in critically ill patients

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. 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. The files give all data for calculating whole body protein kinetics and the amino acids and urea concentrations at the end of the two 24h intervention periods (day 1 and day 2). The file "Tracer infusions" gives the details of the preparation of the tracers infused during the two days, including the volumes taken up in the syringes, the dilutions and the final weight of the syringes. All this information is used to calculate the exact rates of infusion in micromol per kg bodyweight per hour. The file "Enrichments" includes the amount of the tracers (given as Molar Percent Excess) in the blood samples and in the dialysis samples as measured at the different time points during the 5 hours infusion of the tracers. The last 4 samples over the last 15 minutes of the two 24h periods are averaged and used for the calculations of the whole body protein turnover as specified in the publication. The file "Amino acids and Urea" gives the concentrations of all amino acids in plasma and in the dialysate (if appropriate) and of urea in plasma at the end of the two 24h intervention periods (last sample only).Det råder osäkerhet huruvida enteral kaloritillförsel i nivå med uppmätt energibehov (EE) kan minska proteinkatabolism hos intensivvårdspatienter. Studiens syfte var att undersöka huruvida enteral nutrition motsvarande 100% av EE resulterade i en förbättrad helkropps-proteinbalans jämfört med 50% av ordinerad nutrition. Intensivvårdspatienter med invasiv ventilatorbehandling och etablerad enteral nutrition (>80% av EE) rekryterades och randomiserades till hel- eller halv tillförsel av ordinerad näring under 24 timmar, vartefter behandlingen ändrades till den andra tilldelningen i ytterligare ett dygn. Helkropps-proteinbalans bestämdes efter 24 och 48 timmar med stabila isotoptracers. Se beskrivning av datafilerna i den engelska versionen av katalogposte

Whole-body protein kinetics in critically ill patients during 50 or 100% energy provision by enteral nutrition: A randomized cross-over study.

BackgroundEnteral 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.MethodsPatients 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.ResultsSix 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).ConclusionsIt 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

High protein intake without concerns?

Abstract 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

A supplemental intravenous amino acid infusion sustains a positive protein balance for 24 hours in critically ill patients

Abstract 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

An attenuated rate of leg muscle protein depletion and leg free amino acid efflux over time is seen in ICU long-stayers

Abstract Background There is extensive documentation on skeletal muscle protein depletion during the initial phase of critical illness. However, for intensive care unit (ICU) long-stayers, objective data are very limited. In this study, we examined skeletal muscle protein and amino acid turnover in patients with a prolonged ICU stay. Methods Patients (n = 20) were studied serially every 8–12 days between days 10 and 40 of their ICU stay as long as patients stayed in the ICU. Leg muscle protein turnover was assessed by measurements of phenylalanine kinetics, for which we employed a stable isotope-labeled phenylalanine together with two-pool and three-pool models for calculations, and results were expressed per 100 ml of leg volume. In addition, leg muscle amino acid flux was studied. Results The negative leg muscle protein net balance seen on days 10–20 of the ICU stay disappeared by days 30–40 (p = 0.012). This was attributable mainly to an increase in the de novo protein synthesis rate (p = 0.007). It was accompanied by an attenuated efflux of free amino acids from the leg. Leg muscle protein breakdown rates stayed unaltered (p = 0.48), as did the efflux of 3-methylhistidine. The arterial plasma concentrations of free amino acids did not change over the course of the study. Conclusions In critically ill patients with sustained organ failure and in need of a prolonged ICU stay, the initial high rate of skeletal muscle protein depletion was attenuated over time. The distinction between the acute phase and a more prolonged and more stable phase concerning skeletal muscle protein turnover must be considered in study protocols as well as in clinical practice. Trial registration Australian New Zealand Trial Registry, ACTRN12616001012460 . Retrospectively registered on 1 August 2016