Micronutrient trials in critical illness - new evidence since 2023

Numerous trials have tested the impact on outcome of single high to very high doses of micronutrients as adjuvant therapy in severe critical illness and particularly in septic shock. The present review will address the recent knowledge acquired since 2023 including mainly randomized controlled trials (RCTs), but also some quality observational studies.

Eighteen RCTs and nine meta-analyses were reviewed and globally confirm previous findings. Very high MN dose interventions delivered independent of a predisease deficiency in the early phase are not successful. The most frequently used outcomes are duration on vasopressors, length of mechanical ventilation, kidney injury, neurological outcome, biomarkers of inflammation, and mortality. Nosocomial infections are rarely reported, and immunity is rarely addressed while being dependent on micronutrients for optimization. Potential factors impacting study outcomes are discussed, such as the heterogeneity of doses, durations of therapy, primary endpoints, and absence of consideration of the level of inflammation and physiological response.

The recent publications seem to confirm that, in absence of evidence of a prior deficiency, very-high dose MN supplementation is not beneficial and might even be harmful. The heterogeneity of the trial designs compromises definitive conclusions. More trials integrating physiology and status determination are needed to determine the synergistic effect of MN in clinical practice.