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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.    Electronic supplementary material  The online version of this article (10.1186/s13054-017-1932-6) contains supplementary material, which is available to authorized users.

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