Intensive Care Med https://doi.org/10.1007/s00134-025-07937-7
This editorial synthesizes recent high-impact evidence on nutrition and metabolic management for critically ill patients.
- The central theme is a paradigm shift: for acute critical illness, historical approaches of aggressive, early full nutritional support are not only ineffective but can be harmful.
- The authors argue that the acute phase of illness triggers adaptive “fasting responses,” such as autophagy and ketogenesis, which are crucial for repair and recovery.
- Providing full nutrition too early suppresses these beneficial responses and can cause metabolic damage, including worsening hyperglycemia and muscle wasting.
- The recommendation is to avoid full feeding in the first few days of ICU admission, initiating nutrition gradually after the patient stabilizes, while carefully monitoring for metabolic intolerance.
- A similar cautious approach is advised for glucose control, aiming to prevent both severe high and low blood sugar rather than strictly targeting normal levels in all contexts.
Methods
This article is an editorial and expert review, not a primary research study. Its methodology consists of:
- Literature Synthesis:
- The authors have reviewed and interpreted findings from recent major studies, particularly large randomized-controlled trials (RCTs) and mechanistic investigations in the field of ICU nutrition and metabolism.
- Expert Opinion:
- The conclusions and recommendations are based on the authors’ expert interpretation of this body of evidence, including their own extensive research contributions in this area.
Study Population
- The editorial discusses findings relevant to the broad population of critically ill patients, including both adults and children, in the intensive care unit (ICU).
- The summarized RCTs included a wide range of ICU patients, such as those with medical or surgical admission diagnoses and those on mechanical ventilation.
- The piece does not focus on a single pathology but rather the general metabolic response to critical illness.
Statistical Methods
This editorial does not perform its own statistical analysis. It reports on the outcomes of other studies, primarily large RCTs. The validity of its conclusions rests on the statistical rigor of the cited research.
| Statistical Method/Study Design Mentioned | Why It Was Used in the Cited Research |
|---|---|
| Randomized-Controlled Trials (RCTs) | To compare the outcomes of an intervention (e.g., early full nutrition, tight glucose control) against a control or standard care (e.g., late or restricted nutrition) by randomly assigning patients, minimizing bias and allowing for causal inference. |
| Mechanistic Studies | To understand the biological pathways (e.g., autophagy, ketogenesis, ureagenesis) through which an intervention exerts its effects, explaining why an outcome occurred. |
Main Results of the Discussed Evidence
- Providing full nutrition (both energy and protein) within the first few days of critical illness can cause harm, regardless of whether it is given enterally or parenterally.
- Early full nutritional support fails to prevent muscle wasting (catabolism) and does not improve long-term functional outcomes.
- The harm from early feeding is linked to suppressing beneficial processes like autophagy and ketogenesis, and causing metabolic overload (e.g., hyperglycemia, excess urea production).
- Withholding parenteral nutrition for the first week in the ICU was shown to be safe and, in some contexts, superior to starting it early.
- The benefits of tight glucose control are most significant in patients receiving aggressive early nutrition, which worsens hyperglycemia. In the absence of early aggressive feeding, the benefit is less pronounced.
Main Conclusions
- Avoid Full Feeding Early: Full nutritional support should be avoided in all ICU patients during the first few days after the onset of critical illness.
- Go Slow: Start enteral nutrition after the patient is stabilized from the hyperacute phase and increase the dose gradually.
- Delay Parenteral Nutrition: If enteral feeding is not feasible, parenteral nutrition can be safely withheld until after day 4-7 of the ICU stay.
- Monitor Metabolism: we should monitor biochemical markers like urea, glucose, and phosphate for signs of metabolic intolerance to feeding
- Balance Glucose Control: The primary goal of glucose management should be the avoidance of severe hyperglycemia and hypoglycemia. The ideal target range depends on the context, particularly the nutritional strategy
Questions and Doubts Raised
- The editorial states that good markers to identify when a patient transitions from “anabolic resistance” to “feeding responsiveness” are lacking. How can we develop and validate reliable, real-time biomarkers for this transition to truly personalize nutritional therapy?
- The authors suggest a theoretical rationale to reduce nutrition again if a patient suffers a second severe insult later in the ICU stay. What level of evidence exists for this “second-hit” nutritional restriction, and how would clinicians determine its appropriate timing and depth?
- Given that both feeding and insulin suppress protective autophagy and ketogenesis, what is the net effect of using insulin to control feeding-induced hyperglycemia? Are we trading one harm for another?
- The editorial proposes future strategies like intermittent feeding and ketogenic diet]]s. How can we design trials to test these complex interventions against a “go slow” continuous feeding strategy, and what are the most important primary outcomes to measure (e.g., organ failure, functional recovery, mortality)?
Guidance on Follow-up Questions
Question: What can I learn from this editorial that relates to ICU patients with severe burns?
- The “less may be more” nutritional paradigm, which challenges traditional aggressive feeding, should it apply to severe burn patients – a group characterized by the most extreme hypermetabolic and catabolic state seen in medicine?
- Background:
- The Classic Burn Nutrition Paradigm: Traditionally, severe burn injury (e.g., >20% Total Body Surface Area) is considered a state of extreme hypermetabolism and hypercatabolism. For decades, the standard of care has been aggressive and very early enteral nutrition (within 24 hours) with high protein and calorie targets to counteract this catabolic state, preserve gut integrity, and modulate the immune response.
- Connecting to the Editorial’s Concepts: The core principles discussed in the editorial are highly relevant, even if the specific population wasn’t burns.
- Anabolic Resistance: Burn patients are known to have profound and prolonged anabolic resistance. This means that, especially in the early “ebb” phase (the first ~48-72 hours) post-injury, their bodies cannot effectively use the amino acids and energy provided to build protein. Forcing high-dose nutrients during this period may not build muscle but instead fuel the detrimental pathways mentioned in the editorial: increased ureagenesis, hyperglycemia, and oxidative stress.
- Autophagy: The cellular repair process of autophagy is critical for recovery from any severe injury, including burns. The editorial’s central warning—that early full feeding suppresses this vital process —is therefore a crucial consideration. Suppressing autophagy in a burn patient could theoretically impair wound healing and organ recovery.
- Iatrogenic Harm: The risk of iatrogenic hyperglycemia from overfeeding is particularly high in burn patients, who are already insulin resistant. Such hyperglycemia is known to increase the risk of infection and mortality.
- Synthesizing the Evidence: While this editorial does not cite burn-specific RCTs, its conclusions are based on large trials in general ICU patients, some of whom may have had trauma or shock, states which share features with burns. The fundamental biological principles likely apply. The key difference is one of degree and duration. The hypermetabolic “flow” phase in burns is more intense and prolonged than in almost any other critical illness. Therefore, the lesson is not necessarily to starve burn patients, but to reconsider the timing and aggressiveness of initial feeding. The editorial’s advice to “gradually initiate and advance enteral nutritional support after stabilization” is a very relevant and likely safer principle than a one-size-fits-all aggressive target from day one.
- Perhaps the question for burn patients should shift from “if we should feed early” to “how should we feed early”. Could a strategy of initial trophic feeding (a very small amount) to maintain gut health, while allowing for beneficial autophagy, be followed by a more rapid escalation of nutrition as soon as objective markers show the hyperacute phase is resolving? The future may lie in finding better markers than heart rate and blood pressure to signal this transition point in burn patients.