1. Introduction

Early, systematic use of enteral nutrition (EN) leverages the gut’s barrier and immune functions to reduce complications and support metabolism in ICU patients.

A. Epidemiology and Incidence

• EN is initiated within 24–48 hours in 60–80% of ICU patients, but goal calories often fall below 60% due to interruptions and intolerance.
• Underutilization occurs in 30–50% of eligible patients, contributing to increased infections and longer ventilation.
• Reported feeding intolerance (FI) ranges from 2–75%, driven by variable definitions (nausea, diarrhea, high gastric residuals).

B. Clinical Rationale for ENS

EN preserves gut integrity, modulates immunity, and attenuates stress catabolism, offering advantages over parenteral feeding.

• Maintains villus architecture and tight-junction protein expression, reducing bacterial translocation.
• Stimulates gut-associated lymphoid tissue (GALT) and secretory IgA, downregulating proinflammatory cytokines (TNF-α, IL-6).
• Promotes release of trophic hormones (gastrin, CCK) and incretins (GLP-1), improving nutrient absorption and glycemic control.

2. Pathophysiology Underlying ENS

Critical illness impairs mucosal barrier, immunity, and digestion; EN delivers luminal substrates that restore these functions.

A. Preservation of Gut Barrier Integrity

• Critical illness leads to mucosal atrophy, increased permeability, and subsequent endotoxin translocation.
• Even minimal (“trophic”) EN at 10–20 mL/h can sustain epithelial cell turnover and preserve tight-junction integrity.

B. Modulation of Immune and Stress Responses

• Early EN downregulates acute-phase reactants and supports gut-associated lymphoid tissue (GALT).
• It is associated with reduced rates of ventilator-associated pneumonia and other systemic infections compared to delayed or no EN.

C. Nutrient Absorption and Hormonal Signaling

• Luminal nutrients trigger the release of GLP-1 and peptide YY, which enhances insulin secretion and gut motility.
• This helps prevent the severe hyperglycemia and electrolyte shifts associated with parenteral nutrition. However, clinicians must still monitor carefully for refeeding syndrome (hypophosphatemia, hypokalemia, hypomagnesemia) as feeds are advanced.

3. Influence of Chronic Disease States

Comorbidities alter GI motility, nutrient requirements, and EN tolerance. Formulations and strategies must be tailored to the individual patient’s underlying conditions.

A. Cardiovascular Disease and ENS Tolerance

B. Diabetes Mellitus and Glycemic Variability

• EN stimulates incretins, which can help improve post-prandial glycemic control compared to parenteral nutrition.
• Frequent glucose monitoring and proactive insulin adjustment are essential. Wide glycemic swings should be avoided as they can impair immune function and worsen outcomes.

C. Renal and Hepatic Dysfunction – Metabolic Considerations

Patients with organ dysfunction require specialized formulas to meet nutritional needs while avoiding metabolic complications.

4. Social Determinants of Health

Health literacy, access barriers, and cultural factors significantly shape the ability to initiate EN in a timely manner and ensure adherence, particularly after hospital discharge.

A. Health Literacy and Patient Engagement

• Low health literacy can delay the recognition of malnutrition by patients and caregivers and may lead to poor adherence with complex tube care regimens at home.
• Employ strategies like the teach-back method, provide simplified visual aids for formula preparation, and ensure comprehensive caregiver training before discharge to reduce complications.

B. Medication and Formula Access Barriers

• Insurance coverage and restrictive formularies may limit access to specialized or calorically dense products needed by the patient.
• Early involvement of social workers and clinical pharmacists is crucial to navigate prior authorizations, identify financial assistance programs, and arrange for reliable home delivery of supplies.

C. Socioeconomic and Cultural Factors

• Religious beliefs (e.g., desire for kosher or halal products) or cultural dietary preferences can affect patient and family acceptance of standard formulas.
• When possible, inquire about these preferences and work with dietitians to find acceptable commercial formulas or, if necessary, develop a plan using blenderized tube feeds or supplements that meet both cultural and caloric needs.

5. Key Decision Points and Controversies

Decisions on timing, the definition of intolerance, and equitable delivery are central to developing effective ENS protocols and improving patient outcomes.

A. Early vs. Delayed Initiation

• Guidelines strongly recommend initiating EN within 24–48 hours of ICU admission once a patient is hemodynamically stable.
• In unstable patients on vasopressors, the consensus is to start trophic feeds (10-20 mL/hr) and avoid advancing to goal rate until the mean arterial pressure (MAP) is consistently ≥60 mm Hg and vasopressor doses are stable or decreasing.

B. Defining and Managing Feeding Intolerance

• Feeding intolerance (FI) is a clinical diagnosis that may include GRV >250–500 mL, vomiting, significant diarrhea, or abdominal distension with pain.
• First-line prokinetic agents include metoclopramide (10 mg IV q6h) or erythromycin (200 mg IV q8h). Note that the prokinetic effect of erythromycin often wanes after 72 hours due to tachyphylaxis.

C. Equity and Ethical Considerations in ENS Delivery