Annually, more than 90,000 patients are admitted to intensive care units (ICUs) in the Netherlands. As in-hospital mortality has dropped to 15%, 85% percent of patients are discharged alive from the hospital. However, a large number of patients have acquired weakness, and functional disabilities. Many have to be transferred to rehabilitation centers or nursing homes and young patients cannot return to work. For many patients, post-ICU hospital discharge is the beginning of a long journey of physical, cognitive and/or mental health problems. Currently, awareness and recognition of these symptoms, known as post-intensive care syndrome (PICS), is limited. Moreover, there is no consensus on best treatment strategies. This may be due to the lack of understanding of the pathophysiological processes and risk factors underlying PICS. Whether chronic low-grade inflammation in PICS is the major driver of persistent catabolism limiting the benefit of traditional nutritional supplements, or whether other metabolic changes are underlying causes in this condition, needs to be further investigated. Several studies have been performed in the acute phase of critical illness focusing on reducing mortality rates, however longitudinal research in the post-ICU phase is scarce. This paucity of knowledge has resulted in a lack of effective treatment strategies for post-ICU patients with PICS. Recently, long COVID, the long-term consequences of COVID-19 infections, have gained attention. We believe similar mechanisms are involved here, undistinguishable from PICS. Therefore, in depth characterization of the patients in the acute phase and subsequent longitudinal follow-up research after ICU discharge as proposed in this project is essential to explain why some patients recover and others do not.
The insights and research in this project proposal may guide us to optimize the treatment strategy of these patients and design targeted nutritional interventions that contribute to accelerated and improved recovery.

With the prospective observational research in this project proposal, we aim toward an in-depth and comprehensive insight into the pathophysiological characteristics that predict poor functional recovery outcomes after critical care. With the nutritional interventions nested within the prospective cohort, we aim to explore the potential of targeted nutritional intervention strategies to minimize the risk of complications and improve long-term functional recovery.
We expect that the project will help to:
define predictive signatures for long-term functional outcome and quality of life (WP2,5).
identify novel, and select relevant targets for new nutritional intervention strategies (WP2,5).
create proof of concept data to evaluate the potential of high protein tube feed interventions during critical care in the ICU (WP3).
explore the potential of combined exercise and nutritional intervention strategies after critical care by targeting the nutritional status, inflammation and immune fitness, the gut microbiome, brain health and muscle function in a multimodal rehabilitation program following hospital admission after ICU stay (WP4)

This project nicely fits the mandate of TKI Agri&Food and Mission D "Valued, healthy and safe food," as defined in the topsectoren Agri&Food 2022 call. When developing nutritional supplements or food solutions for this most vulnerable target group, it is essential to fully understand their nutritional needs and metabolic response to food administration. This personalized strategy will ensure that these solutions are safe and deliver relevant benefits to these target populations. With this project, we aim to develop new and safe intervention strategies to maximize the recovery potential of critical care patients.

Today longitudinal studies to follow post-ICU patients are scarce. The few studies describe a high prevalence of poor longer-term functional outcomes with a high burden for the patient and the health care system. However, prospective studies with an in-depth assessment of patients' characteristics and systemic analysis of correlations predictive of poor outcomes are lacking. The core study of this project aims to identify predictive signatures and will allow us to define targets to optimize the care for ICU and post-ICU patients with improved intervention strategies targeting the physiological alterations present in (post) ICU patients. Outcomes of this prospective research in (post) ICU patients will also help us to understand better the (nutritional) needs of other severely ill patients suffering from long-term (i.e. long COVID) to maximize their chances for optimal recovery.
Next to the prospective observational research, the project includes two nested proof-of-concept studies
help guide intensivists to choose optimized protein feeding during ICU stay
enables us to determine the potential and effect size of targeted exercise and nutritional interventions towards physiological processes that are likely to be compromised in patients recovering from ICU stay.