Another vital macronutrient that needed to be provided was protein. Initial experiments in the 1930s were done with plasma as the protein source, and investigators achieved positive nitrogen balance. In the early 1900s, research began on the development of protein hydrolysates and crystalline amino acids. Vitrum, a Swedish company, produced the first commercially available casein hydrolysate solution. It was developed by Arvid Wretlind, who hydrolyzed casein enzymatically and then dialyzed the mixture to remove large polypeptides. The crystalline amino acid solutions that we are more familiar with were first developed by Bansi in 1964. Wretlind went on to modify it further and eventually replaced the hydrolysates in the 1970s.

The development of amino acid solutions specifically for infants occurred in the early 1980s. These solutions provided conditionally required amino acids for the immature organ systems of premature infants and newborns. They were formulated based on the postprandial plasma amino acid levels of breast-fed infants. Special amino acid solutions for renal or liver failure are also available that have increased amounts of branched-chain amino acids. Studies on the solutions for liver failure have shown that they are probably beneficial in adult patients with encephalopathy. Glutamine is a much researched amino acid that could not initially be added to PN solutions due to shelf instability in liquid form. When added as a dipeptide, it has been found to be more stable. Not all studies have shown clear benefit to its addition in patients for gut adaptation or prevention of bacterial translocation.

The recommendation for initiation of protein is 1 g/kg/day and that for advancement is 1 g/kg/day to goal (Table 2). Blood urea nitrogen is monitored for tolerance to amino acid infusion.

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