The Energy Intake: How Much, and at What Time?

Although numerous observational studies have associated a cumulative energy deficit with impaired outcome of critically ill patients, large-scale randomized controlled trials have shown that early nutritional support induces dose-dependent harm, regardless of the route of feeding and irrespective of the anticipated nutritional risk. Likewise, early indirect calorimetry-based nutritional support and early high-dose protein supplements did not benefit critically ill patients. The lack of benefit of early full nutritional support has been explained by anabolic resistance and by suppression of beneficial recovery pathways that are induced by fasting, including autophagy and ketogenesis. This opens perspectives for intermittent feeding/fasting strategies, ketogenic diets, and ketone administration to exploit fasting-induced benefits while avoiding prolonged starvation, which should be further investigated. The time point when anabolic resistance switches into feeding responsiveness is likely dynamic and can hitherto not be monitored or predicted. Future studies should investigate markers of readiness of feeding, as well as early markers of under- and overfeeding, which would allow true individualized nutritional support. In the absence of new evidence, hypocaloric nutrition is advised in the acute phase, whereas full nutritional support is recommended from the second week in the intensive care unit onward.