Rationale for Enteral Nutrition in Critically Ill Adults

Mechanically ventilated adults cannot eat by mouth, making enteral nutrition (EN) a major part of supportive care. Over the past 20 years, research has improved understanding of critical illness phases, body responses, and the role of EN in critically ill adults.

A recent narrative review provides an overview of EN by outlining the phases of critical illness, explaining the biologic reasons for EN, reviewing recent studies on timing and dosing of EN, discussing protein needs and related studies, highlighting key monitoring aspects during EN, and identifying research gaps and priorities in critical care nutrition.

Early EN is a key therapy in critically ill adults, with guidelines historically recommending full-dose feeding within 72 hours of ICU admission. However, dosing should align with the phase of critical illness, as a restrictive dose during the acute phase can protect gut integrity, support the microbiome, and modulate immune responses. Recent trials show that full-dose feeding during the acute phase may cause harm by adding stress, leading to worse outcomes. Although critically ill adults experience muscle breakdown, high-dose protein has not improved outcomes and may be harmful in some patients.

In critical illness (e.g., septic shock, burns, trauma, respiratory failure), the body’s stress response prioritises survival through hormone activation while reducing processes like growth and long-term immunity. In 2018, the European Society for Enteral and Parenteral Nutrition refined the “ebb and flow” model into acute and late phases:

• Early acute phase (days 1–3): metabolic instability, inflammation, high catabolism, focus on resuscitation and source control.
• Late acute phase (days 3–7): metabolic stabilization, de-escalation of support, start of rehabilitation.
• Recovery phase (after day 7): convalescence and anabolism, with rehabilitation as the primary goal.

Transitions between phases are unclear and may fluctuate, with patients potentially returning to earlier phases if complications occur.

Early EN, compared to delayed EN, no EN, or parenteral nutrition, helps preserve gut function by maintaining mucus and antimicrobial protein secretion, tight junction integrity, and gut immune responses (regulatory T cells, Peyer’s patch lymphocytes, IgA). Early EN also supports the growth of beneficial gut bacteria.

EN started within 24–36 hours improves outcomes in critically ill adults compared to delayed or no EN, reducing infections, mortality, and ICU/hospital stay. Guidelines recommend initiating EN within 24–48 hours if there are no contraindications. However, the optimal EN dose during the first week of critical illness is debated. Contemporary RCTs and meta-analyses show no outcome benefit of early full-dose EN over restrictive strategies (permissive underfeeding, hypocaloric, trophic feeding) and suggest restrictive EN may be safer during the acute phase.

Reasons restrictive EN may be preferable include:

1. GI intolerance: Ileus and dysmotility are common early; full-dose EN increases GI complications.
2. Shock risk: Full-dose EN in patients on high-dose vasopressors increases bowel ischaemia risk.
3. Hyperglycemia: Full-dose EN worsens hyperglycaemia and insulin needs during acute illness.
4. Mitochondrial dysfunction: Full-dose EN increases oxidative stress, while restrictive feeding supports lactate clearance.
5. Refeeding syndrome: Rapid advancement to full-dose EN increases refeeding risk and mortality in malnourished patients.
6. Fluid overload & CO₂ burden: Full-dose EN may cause volume overload and increase CO₂, delaying ventilator weaning.
7. Autophagy inhibition: Restrictive EN may better support autophagy, aiding recovery.

While early EN supports gut function, restrictive dosing during the first week of critical illness may reduce complications, align better with metabolic needs, and improve outcomes compared to early full-dose EN.

Critically ill adults lose ~2% of skeletal muscle daily during the first ICU week, with muscle weakness seen in ~48% of patients, increasing the risk of long-term functional impairment. While providing sufficient protein became central in nutrition therapy, anabolic resistance in critical illness limits protein utilisation for muscle synthesis, with studies showing critically ill adults incorporate only 60% of absorbed amino acids into muscle.

Higher protein dosing was hypothesised to overcome anabolic resistance and improve outcomes, supported by small studies showing improved nitrogen balance and surrogate markers. However, large multicentre RCTs (EFFORT, PRECISe) found high-dose protein (≥2 g/kg/day) did not improve clinical outcomes over standard doses (1.2–1.3 g/kg/day) and may cause harm in patients with high illness severity or acute kidney injury, including higher mortality, refeeding hypophosphatemia, and GI intolerance.

In malnourished patients, higher protein dosing did not modify poor outcomes. Most evidence comes from medical ICU patients, leaving the optimal protein dose in surgical, trauma, and burn patients uncertain.

Overall, the review highlights that high-dose protein does not improve outcomes compared to standard-dose in critically ill adults. It may worsen outcomes in sicker patients and those with kidney dysfunction. Recent meta-analyses confirm high-dose protein is ineffective in improving critical care outcomes. There are no standardised criteria for enteral feeding intolerance (EFI), but clinical signs are categorised as low-risk or high-risk. Low-risk signs include gastric distention, ileus, abdominal pain, nausea, vomiting, constipation, and obstipation, while high-risk signs are nonocclusive mesenteric ischaemia, bowel necrosis, and abdominal compartment syndrome.

Low-risk signs should not automatically prompt stopping EN but must be evaluated considering illness severity. In critically ill patients with severe disease, especially those in circulatory shock on high-dose vasopressors and full-dose EN, low-risk signs may signal impending high-risk complications, warranting a lower threshold to reduce or hold EN.

The NIH 2020–2030 Strategic Plan emphasises advancing precision nutrition and tailoring nutrition to individual patient factors rather than using a “one size fits all” approach. Critical care nutrition trials suggest treatment effects may vary among patients, highlighting the need to identify who benefits most from different timing and doses of EN. Biomarkers are needed to predict patients’ nutrition tolerance and anabolic response, especially since transitions between critical illness phases are unclear.

While most trials focus on EN during the acute phase, more research is needed on individualised nutrition support during the late and post-ICU phases to improve patient-centred outcomes.

Source: Critical Care Medicine

Image Credit: iStock