Amino acid kinetics in the critically ill

Abstract

Purpose of review Stable isotope methods have been used for many years to assess whole body protein and amino acid kinetics in critically ill patients. In recent years, new isotope approaches and tracer insights have been developed. The tracer pulse approach has some advantages above the established primed-continuous tracer infusion approach because of the high amount of metabolic information obtained, easy applicability, and low tracer costs. Effects of disease severity and sex on amino acid kinetics in ICU patients will also be addressed. Recent findings Current knowledge was synthesized on specific perturbations in amino acid metabolism in critically ill patients, employing novel methodologies such as the pulse tracer approach and computational modeling. Variations were evaluated in amino acid production and linked to severity of critical illness, as measured by SOFA score, and sex. Production of the branched-chain amino acids (BCAAs), glutamine, tau-methylhistidine and hydroxyproline were elevated in critical illness, likely related to increased transamination of the individual BCAAs or increased breakdown of proteins. Citrulline production was reduced, indicative of impaired gut mucosa function. Sex and disease severity independently influenced amino acid kinetics in ICU patients. Summary Novel tracer and computational approaches have been developed to simultaneously measure postabsorptive kinetics of multiple amino acids that can be used in critical illness. The collective findings lay the groundwork for targeted individualized nutritional strategies in ICU settings aimed at enhancing patient outcomes taking into account disease severity and sex.

Compartmental analysis: a new approach to estimate protein breakdown and meal response in health and critical illness

“…PB measured with the KIC plasma enrichment is 1.3 times higher than when using the leucine plasma enrichment ( 15 ). In contrast, using the pulse approach, PB appears to be 2.6 times higher when calculated with the intracellular appearance of leucine than when calculated with Ra ( 4 ). Therefore, using plasma KIC enrichment to better estimate PB is not sufficient to correctly estimate intracellular PB.…”

“…By measuring the phenylalanine production in healthy and critically ill patients ( Figure 1 ), we can calculate the turnover of protein per gram protein/day/subject ( Table 1 and Supplementary Figure S1 ) ( 4 ). As previously reported by others ( 13 ), ~300 grams of protein are broken down per day in a healthy individual in the postabsorptive state ( 4 ) as measured by the primed-constant and continuous stable isotope infusion protocol. If food only increases protein synthesis (see later), a dietary intake of approximately 75 grams of balanced protein would enhance protein synthesis to 375 grams, which is an ~25% increase.…”

“… Data are grams of protein/day [mean (95% CI)] protein breakdown (PB), obtained from recalculation of data, described previously ( 4 ). We used phenylalanine and tyrosine decay curve parameters to calculate the non-compartmental PB (comparable to the rate of appearance in plasma), intracellular production, and net protein breakdown, using the conversion of phenylalanine to tyrosine.…”

“…Protein turnover in healthy individuals and during a variety of disease states, including critical illness, has predominantly been calculated using traditional methods such as primed-constant and continuous infusion of combinations of stable isotope amino acids such as leucine, phenylalanine, and tyrosine ( 7 , 8 ). This approach requires intravenous infusion of stable amino acid tracers using a calibrated pump and accurate priming of the tracer pool to instantly obtain a tracer steady state, which is not always easy ( 4 ).…”

“…Recently, we reported a novel pulse tracer approach that enables the calculation of the intracellular production of amino acids ( 2–4 , 9 , 10 ). When using this approach, a pulse of stable isotopes is administered intravenously in a small volume and within 10 s. Measuring the decay of the isotope enrichments in plasma makes it possible to calculate simultaneously both the whole-body production (WBP) rate of these amino acids [is equal to the non-compartmental rate of appearance (Ra) as calculated by the primed-constant and continuous infusion model ( 7 , 8 )], and the intracellular production rate ( 3 , 4 ) from the compartmental analysis. We have used this approach to compare the WBP and intracellular production of amino acids to better understand the balance between protein degradation rate and dietary protein intake ( Figure 1 ).…”