Short-term amino acid infusion improves protein balance in critically ill patients

Abstract

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.

Figure 1

Plasma enrichments (A) and rate of appearance (B) measured with ¹³ C-phenylalanine intrinsically labeled casein protein (35.2 molar percent excess (MPE)) and with the same amount of free [ ² H ₅ ]phenylalanine (99.7 MPE) given enterally together with maltodextrin in six critically ill patients for 6 hours. The rate of appearance is an apparent rate of appearance of phenylalanine (not corrected for splanchnic extraction) into the central circulation and is calculated by dividing the enteral infusion rate of the two tracers by the plasma enrichment of each tracer at each time point. In one patient, none of the tracers escaped the splanchnic tissues, so mean values and standard deviations of five patients are shown. After about 4 hours, the rate of appearance was identical for both tracers. The individual data for these patients are given in Additional file 1.

Figure 2

CONSORT diagram of the number of patients included into the study. Because of the pragmatic nature of the study, the cohorts of patients studied to answer the three research questions were not identical. ICU, Intensive care unit.

Figure 3

Sum of all amino acids in plasma of critically ill patients during baseline and parenteral amino acid supplementation (AA) on 2 study days. On the first study day, 13 patients were studied, and on the second study day, 7 of these patients were still being treated in the intensive care unit and were studied again. The seven patients studied twice are indicated by continuous lines, and the other five studied on day 1 only are indicated by dashed lines. Individual values are shown, with the median in red. The sum of amino acids consists of glutamate, serine, glutamine, histidine, glycine, threonine, arginine, alanine, tyrosine, valine, methionine, tryptophan, phenylalanine, isoleucine, leucine and lysine.

Figure 4

Whole-body protein breakdown (A), protein synthesis (B), protein balance (C) and phenylalanine oxidation (D) in critically ill patients during baseline and parenteral amino acid supplementation (AA) on 2 study days. On the first study day, 13 patients were studied, and on the second study day, 7 of these patients were still being treated in the intensive care unit and were studied again. The seven patients studied twice are indicated by continuous lines, and the other five studied on day 1 only are indicated by dashed lines. Individual values are shown, with the median in red.

Figure 5

Plasma urea concentrations in critically ill patients during baseline and parenteral amino acid supplementation (AA) on 2 study days. On the first study day, 13 patients were studied, and on the second study day, 7 of these patients were still being treated in the intensive care unit and were studied again. The seven patients studied twice are indicated by continuous lines, and the other five studied on day 1 only are indicated by dashed lines. Individual values are given, with the median in red.

Figure 6

Statistical correlations between total amino acid and/or protein feeding and whole protein balance (A) and protein oxidation rate (B) in 13 critically ill patients during baseline and parenteral amino acid supplementation (AA) on 2 study days. On the first study day, 13 patients were studied, and on the second study day, 7 of these patients were still being treated in the intensive care unit and were studied again. All measurements performed for all patients are included. The protein balance is presented in grams of protein per kilogram of body weight per day. This was calculated assuming that the phenylalanine content of the human whole-body protein pool is 4% [12]. A positive correlation with r =0.80 (P <0.0001) was observed between the amino acid and/or protein feeding and whole-body protein balance. No correlation with phenylalanine oxidation was observed (r =0.02; P =0.88).