When should parenteral nutrition (PN) be initiated in critically ill patients?

When to Initiate Parenteral Nutrition in Critically Ill Patients

Parenteral nutrition (PN) should be initiated after 3 days if enteral nutrition (EN) cannot be started or remains insufficient, but only after attempting enteral feeding first in hemodynamically stable patients. 1, 2

Primary Approach: Enteral Nutrition First

• Attempt enteral nutrition within 48 hours of ICU admission in all hemodynamically stable patients with functioning gastrointestinal tracts, as this is the preferred route that reduces infectious complications by 50% compared to early PN (relative risk 0.50,95% CI 0.37-0.67). 1, 2

• Start EN at low rates (10-20 mL/hour) while carefully monitoring for gastrointestinal intolerance, then increase slowly as tolerated. 1

• Target approximately 70% of measured energy expenditure during the acute early phase (days 1-2), avoiding full feeding which has been shown to cause harm. 1

When to Initiate Parenteral Nutrition

Timing Algorithm:

Day 1-2 (Acute Early Phase):

• Continue attempting EN at low doses (20-50% of full nutrition support) to "open" the enteral route. 1
• Do not start PN during this period unless EN is absolutely contraindicated. 1

Day 3-7 (Acute Late Phase):

• Initiate PN if EN remains insufficient or not feasible after 3 days, providing approximately 50% of predicted or measured energy needs (not full feeding). 1, 2
• This applies specifically to patients with expected ICU stay longer than 3 days and organ failure (SOFA score >4). 1, 2

After Day 7 (Recovery Phase):

• Continue or initiate PN if oral/enteral intake remains inadequate, now targeting full energy requirements. 1

Absolute Contraindications to Enteral Nutrition (When PN Should Be Started After Day 3):

• Uncontrolled shock with hemodynamic instability 1
• Uncontrolled hypoxemia and acidosis 1
• Uncontrolled upper GI bleeding 1
• Gastric aspirate >500 mL per 6 hours 1
• Bowel ischemia or mesenteric ischemia 1
• Bowel obstruction or discontinuity 1
• Abdominal compartment syndrome 1
• High-output fistula without distal feeding access 1

Critical Evidence on Timing

The EPaNIC trial (n=4,640 patients) demonstrated that late initiation of PN (started on day 8) resulted in better outcomes than early PN (within 48 hours), including increased proportion of patients discharged alive (HR 1.06, p=0.04), reduced infectious complications (22.8% vs 26.2%, p=0.008), and shorter duration of mechanical ventilation. 1 This landmark study fundamentally changed practice by showing harm from early aggressive nutrition.

However, the 2019 ESPEN guidelines balance this by recommending PN initiation after 3 days when EN is insufficient, representing a pragmatic middle ground between immediate feeding and waiting a full week. 1

Dosing Strategy When PN Is Initiated

Acute Phase (Days 3-7):

• Provide 20-25 kcal/kg/day (approximately 50% of full needs) to avoid overfeeding. 1, 2
• Protein: Start low (<0.8 g/kg/day) early, then progress to 1.3-1.5 g/kg/day as patients stabilize. 1, 2

Recovery Phase (After Day 7):

• Increase to match measured energy expenditure using indirect calorimetry when available. 1
• Target protein delivery ≥1.2 g/kg/day. 1

Administration Requirements

• Central venous access is required for high osmolarity PN mixtures designed to cover full nutritional needs (>850 mOsmol/L). 1, 2
• Peripheral PN can be considered only for low osmolarity solutions (<850 mOsmol/L) providing partial nutrition support. 1

Supplemental PN Strategy

When EN is started but remains insufficient after 3 days:

• Add supplemental PN to reach approximately 50% of energy targets rather than continuing inadequate EN alone. 1
• Recent meta-analysis showed supplemental PN combined with EN decreased nosocomial infections (RR 0.733, p=0.032) and ICU mortality (RR 0.569, p=0.030) compared to EN alone. 3
• Energy deficits correlate strongly with infectious complications, duration of mechanical ventilation, and ICU length of stay. 1, 2

Critical Pitfalls to Avoid

• Never provide full feeding (100% of energy needs) in the first 3-7 days, as this causes harm including increased infections and prolonged ICU stay. 1
• Do not start PN within the first 48 hours unless EN is absolutely contraindicated, as early PN increases infectious complications. 1, 2
• Avoid overfeeding at any time, maintaining blood glucose between 4.5-10 mmol/L, as hyperglycemia increases mortality and infectious complications. 2
• Do not delay PN beyond 3 days in patients who cannot receive adequate EN, as progressive energy deficits worsen outcomes. 1, 2, 4
• Correct severe electrolyte abnormalities (hypokalemia, hypomagnesemia, hypophosphatemia) before initiating PN to prevent refeeding syndrome. 5

Special Populations

Sepsis/Septic Shock:

• After successful resuscitation, provide 20-50% of nutrition support early, then increase gradually according to GI tolerance once hemodynamic alterations resolve. 1
• If EN not feasible, start PN after resuscitation at approximately 50% of energy needs. 1

Post-Surgical (Abdominal/Esophageal):

• Prefer early EN over delayed EN when GI tract is intact. 1
• Start PN only if anastomotic leak, fistula, or GI discontinuity present and distal feeding access cannot be achieved. 1