## 3 Assessment of Medical Nutrition Therapy
### Protein Needs  
Although the coverage of energy needs is an area that has been studied for several years, the importance of the protein needs has only recently become a subject of focus. Indeed, critical illness causes protein catabolism resulting in important muscle loss, which influences a patient's survival and clinical outcome [81]. Current recommendations on protein intake for critically ill patients are based mainly on observational data and only a few RCTs having different designs. Thus, it is difficult to draw definitive conclusions.  
Various recent observational studies have focused on the association between protein intake and patients' clinical outcomes, suggesting an association between mortality reduction and protein intake [82; 83; 84]. For instance, decreased mortality has been related to protein intake \(\geq\)1.2 g/kg/day in non-septic and non-overfeed critically ill patients [84] by achieving \(\geq\)80% of the prescribed protein intake [82] and to a protein intake of \(>\)1 g/kg/day [83].  
Conversely, recent RCTs on protein needs have shown contradictory results and up-to-date no mortality benefit with higher amino acid intake could be shown by RCTs. In the Ferrie study (\(n=120\)), the administration of 1.2 g/kg parenteral amino acids (AA) compared to 0.8 g/kg was associated with attenuated muscle wasting, less fatigue, and better nitrogen balance, but no difference in mortality or length of stay was observed [85].  
The Nephro-Protective trial (\(n=474\)), with higher AA administration in the intervention group, did not affect the duration of renal dysfunction but only showed an improved estimated glomerular filtration rate (eGFR) and daily urinary output. Furthermore, serum urea was significantly higher, with a trend toward increased renal replacement therapy (RTT) in patients receiving AA therapy, which was not present after controlling for baseline imbalance in terms of renal failure at the time of study enrollment [86].  
Other recent RCTs, such as the EAT-ICU (\(n=203\)) and the TOP-UP trial (\(n=125\)) on protein needs, have confirmed no differences on clinical outcomes including mortality, hospital stay, days of ventilation, nosocomial infections, or organ failure rates [53; 56]. However, the EAT-ICU trial also showed a prolonged ICU length of stay (post-hoc analysis) as well as a trend to increased plasma urea levels in the Early Goal-directed Nutrition group [56].  
The EPaNIC trial (\(n=4640\)) showed that early initiation of parenteral nutrition (PN) was associated with a longer course of RTT and a longer ICU stay. Similar functional status was observed in the early and late PN group [54]. A prospectively planned subanalysis of the EPaNIC trial found an increased incidence of ICU-acquired muscle weakness with slower recovery in the early-PN group [87].  
Apart from this, in another post hoc analysis of the EPaNIC trial, delayed recovery was also attributed to the early administration of amino acids by PN [88].  
The results of the recent RCTs underline the urgent need for further studies to provide answers to questions still outstanding, such as the right amount of protein to administer and the best timing.  
Based on the available results and without the possibility to assess individual protein needs during a protein-loss phase, ESPEN guidelines [17] suggest a progressive provision of 1.3 g/kg/day of protein equivalent during critical illness (grade 0). In contrast, the ASPEN guidelines [27] propose a protein intake of 1.2-2.0 g/kg/day (grade very low).  
Exercise in combination with achieving protein targets has also been suggested to maximally maintain muscle mass [17; 89; 90].