Lessons from pharmacokinetics in the design of new nutrition formulas for critically ill patients.

Severe injury causes alterations in protein metabolism [1], including net muscle protein breakdown, increased transfer of amino acids (AAs) from the peripheral to the splanchnic area, intense use of AAs for gluconeogenesis and consequently a marked increase in nitrogen loss, leading to a negative nitrogen balance [2]. When persistent and/or very severe, this process is responsible for protein wasting and in turn for morbidity and mortality. Nutritional supply must therefore form an integral part of therapeutic strategy in critically ill intensive care unit (ICU) patients. But the qualitative intake of nitrogen has to match the requirements of such patients, which are specific and different from those of healthy subjects [1]. The specificity of their requirements arises from a number of factors, some of which are summarized in table 1. However, because historically the technical aspects were mastered before knowledge of the physiopathological alterations became fully known [3], the specific AA needs of ICU patients unfortunately long went unrecognized, and recommended requirements were merely adapted from those set for healthy subjects. Most products tailored for enteral use supply nitrogen in the form of high nutritional value proteins, and most solutions for parenteral nutrition (PN) provide a mixture of free AAs that reproduce the composition of these high-quality reference proteins (egg and cow milk proteins), namely 45% essential AAs (EAAs) and a ratio of EAAs to total nitrogen of 3.1 mg/g. It is clear that current formulas are unlikely to meet ICU patients’ requirements fully [4]. The key questions that must be addressed are the following: (1) How do we determine the AA requirements of critically ill