Abstract
The rationale for the provision of nitrogen from proteins given via the enteral route or from intravenous amino acids is to boost the synthesis of muscle proteins, and thereby to limit the severity of intensive care unit-acquired weakness by the prevention of muscle loss. However, the optimal timing for supplemental nitrogen provision is a matter of debate and controversy. Indeed, consistent data from retrospective studies support an association between high early protein intakes and better outcomes, while recent post-hoc findings from prospective studies raise safety concerns. This pro–con paper details the arguments of both sides and highlights the need for large-scale prospective studies assessing the safety and efficacy of different levels of protein intake in combination with physical activity and summarizes the currently recruiting clinical trials.
Highlights
A large consensus supports the provision of high protein intakes during the late phase of critical illness, e.g., during recovery when the ability to increase the synthesis of muscle proteins from the pool of circulating amino acids increases [1, 2]
Controversial views are expressed regarding the amount of proteins to be given during the early phase of critical illness, when muscle protein breakdown outweighs muscle synthesis as a result of the resistance to anabolic stimuli [3, 4]
The proportion of nitrogen losses to be compensated by protein intake in the critically ill is a matter of debate, as reflected by recommendations cited in the most recently published guidelines: 1.2–2.5 g/kg of protein per day [5, 6] and the Correspondence: Jean-Charles.Preiser@erasme.ulb.ac.be Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, 808 route de Lennik, B-1070 Brussels, Belgium provision of an amount of protein lower than nitrogen losses [1, 4], in agreement with the “Baby stomach” concept [7]
Summary
Industrial companies recently started to market nutritional formulas containing high amounts of proteins or amino acids and promoted their use early during the course of critical illness, following experts’ opinions mainly based on associations between high nitrogen intakes and better outcomes and on biochemical arguments. The marketing of these solutions is possible as the legal standards do not require the same sequence of testing as for a new drug, i.e., phase I clinical trials to check the safety, phase II clinical trials to assess the efficacy, and phase III clinical trials to compare the new treatment with the current standard of care. A preplanned post-hoc analysis of the PEPaNIC study [33] that evaluated the effects of withholding parenteral nutrition in critically ill children suggests a linear positive
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