Nutritional and metabolic modulation of inflammation in critically ill patients: a narrative review of rationale, evidence and grey areas

Inflammation is the hallmark of critical illness and triggers the neuro-endocrine stress response and an oxidative stress. Acute inflammation is initially essential for patient’s survival. However, ongoing or exaggerated inflammation, due to persistent organ dysfunction, immune dysfunction or poor inflammation resolution, is associated to subsequent hypermetabolism and hypercatabolism that severely impact short and long-term functional status, autonomy, as well as health-related costs. Modulation of inflammation is thus tempting, with the goal to improve the short- and long-term outcomes of critically ill patients.

Inflammation can be modulated by nutritional strategies (including the timing of enteral nutrition initiation, the provision of some specific macronutrients or micronutrients, the use of probiotics) and metabolic treatments. The most interesting strategies seem to be n-3 polyunsaturated fatty acids, vitamin D, antioxidant micronutrients and propranolol, given their safety, their accessibility for clinical use, and their benefits in clinical studies in the specific context of critical care. However, the optimal doses, timing and route of administration are still unknown for most of them. Furthermore, their use in the recovery phase is not well studied and defined.

The rationale to use strategies of inflammation modulation is obvious, based on critical illness pathophysiology and based on the increasingly described effects of some nutritional and pharmacological strategies. Regretfully, there isn’t always substantial proof from clinical research regarding the positive impacts directly brought about by inflammation modulation. Some arguments come from studies performed in severe burn patients, but such results should be transposed to non-burn patients with caution. Further studies are needed to explore how the modulation of inflammation can improve the long-term outcomes after a critical illness.