## 4 Practical Implementation
### Medical Nutrition Therapy: EN, PN, ONS, and Combinations  
Routes, quantity, and timing of nutritional delivery have been widely discussed over recent decades. With the increasing administration of parenteral nutrition (PN) to the critically ill, some studies have shown more infectious complications in comparison to enteral nutrition (EN) [29; 30]. Enteral feeding was subsequently used in first line with an important reduction in the use of PN [108]. However, achieving energy and protein targets with EN alone is difficult during the ICU and IMC-U stay and may result in undernutrition in most patients [31; 32]. Recent RCTs have shown no increase in the rate of complications independent of the chosen route of nutrition [57; 109]. Avoiding under- or overnutrition is more important than the feeding route [108]. The SPN study (\(n=305\)) showed that the use of supplemental parenteral nutrition (SPN) (when EN was insufficient to match the energy targets at day 4 after ICU admission) could reduce nosocomial infections after the end of the intervention and until the end of the observation period (days 9 to 28), as well as antibiotic use during the ICU stay [7]. However, no impact on infections was shown when counting the infection rate from the randomization day onward. The TICACOS pilot study (\(n=130\)) [55] showed, based on prospective intention to treat analysis of the data, that IC-guided nutrition therapy provoked an increase in complications with more infections, longer duration of ventilation, and prolonged ICU stays. A per protocol analysis, on the contrary, suggested a short-lived survival benefit [55]. Some other studies (e.g., EAT-ICU (\(n=203\)) [56], TARGET (\(n=3957\)) [11], EDEN (\(n=1000\)) [13]) showed no difference between the early versus standard initiation groups in primary clinical outcomes, but secondary outcomes revealed hyperglycemia [13; 56] and decreased gastric tolerance [11; 13] in the early nutrition intervention group. The PermiT trial (\(n=894\)) group studied permissive underfeeding (40-60% of calculated caloric requirements) compared to standard enteral feeding (70-100%) with similar protein intake. The results showed no difference in 90-day mortality and no differences in other significant outcomes between the groups [12]. The results of the EPANIC trial (\(n=4640\)) revealed no difference in 90-day mortality but an increased complication rate with early initiation of parenteral support (i.e., infections, longer mechanical ventilation, and length of stay) [54]. The divergence of results may be related to the heterogeneous patient population and highly variable study designs with differences such as the amount of calories administered, the timing of EN or PN initiation, and the use of IC or predictive formulas. Considering these contradictory findings, expert guidelines agree on the following indications for MNT [17; 27]: (1) Oral nutrition should be preferred over EN or PN in patients able to eat voluntarily (GPP). (2) If needed, oral nutritional supplements (ONS) can be given with the aim to achieve energy and protein needs [34]. (3) Early EN (within 48 h) is suggested for all patients with a functional digestive tract who cannot eat voluntarily (grade B). Enteral feeding can be performed progressively after the early phase of the critical illness and, after 3 days, caloric delivery can be increased up to 80-100% of the measured EE (grade 0). (4) In patients who do not tolerate full EN during the first week, initiation of SPN should be considered on a case-by-case basis and should only be started after all strategies to maximize EN tolerance have been attempted (GPP). (5) In case of impossible oral feeding and EN contraindications, PN must also be started progressively during the first week of the ICU stay. The timing of PN initiation is a highly debated topic. ESPEN experts propose an early implementation of PN within 3-7 days in case of contraindications to oral feeding or EN (grade B).