Early Phosphate Changes May Signal ICU Patients' Unreadiness for Artificial Feeding, Study Suggests

The study, published in the BMC journal Critical Care revealed early shifts in phosphate levels could help identify ICU patients who may be adversely affected by early parenteral nutrition (PN). Relative hypophosphatemia (RHP), defined as a decrease in phosphate levels greater than 0.16 mmol/L within the first two days of ICU admission, has been associated with poorer outcomes, including a lower chance of early ICU discharge, in patients receiving early PN. However, predicting RHP based on baseline characteristics remains difficult.

In the EPaNIC randomized controlled trial (RCT), early parenteral nutrition prolonged ICU dependency compared to withholding PN until one week after ICU admission. Conversely, the Refeeding RCT demonstrated improved outcomes by implementing temporary macronutrient restriction in ICU patients who developed refeeding hypophosphatemia, characterized by a phosphate decrease of greater than 0.16 mmol/L, reaching levels below 0.65 mmol/L.

Based on these findings, M. P. Casaer, Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium, and colleagues hypothesized that early phosphate changes could serve as an indicator for critically ill patients who are adversely affected by early PN. Furthermore, they propose that dynamic phosphate fluctuations may be more predictive of harm than an absolute threshold for hypophosphatemia.

In this secondary analysis of the EPaNIC RCT, Dr. Casaer and colleagues examined whether absolute hypophosphatemia (AHP; < 0.65 mmol/L on the second ICU day), relative hypophosphatemia (RHP; > 0.16 mmol/L decrease over the first two ICU days), or a combination of both (CHP) influenced outcomes based on the randomized nutritional strategy, while adjusting for risk factors. In the case of a significant interaction, we further explored whether baseline characteristics could predict the respective phosphate changes.

The study revealed the following findings:

• Among 3520 patients with available phosphate measurements, 9.1% developed absolute hypophosphatemia (AHP), 23.7% developed relative hypophosphatemia (RHP), and 5.3% developed a combination of both (CHP).
• RHP, but not AHP or CHP, interacted significantly with the randomized intervention for its impact on outcomes.
• In patients with RHP, early parenteral nutrition (PN) was independently associated with a lower likelihood of earlier discharge alive from the ICU (adjusted HR 0.75).
• In patients without RHP, early PN did not significantly associate with this outcome (adjusted HR 0.93).
• The development of RHP was poorly predicted by admission characteristics (adjusted pseudo R-squared = 1.7%).

This secondary analysis of the EPaNIC RCT identified that an early decrease in phosphate levels, rather than absolute hypophosphatemia, highlighted patients particularly harmed by early parenteral nutrition.

"These findings suggest the potential for incorporating phosphate changes into a "ready-to-feed" indicator, paving the way for more individualized nutritional support. However, further prospective studies are needed to validate this approach and confirm its applicability in clinical practice," the researchers concluded.

Reference:

Lauwers, C., Langouche, L., Wouters, P.J. et al. Early phosphate changes as potential indicator of unreadiness for artificial feeding: a secondary analysis of the EPaNIC RCT. Crit Care 29, 48 (2025). https://doi.org/10.1186/s13054-025-05273-2