Having previously demonstrated that supplemental parenteral nutrition to complete an insufficient enteral nutrition (EN) between D4 and D8 improves outcome after critical illness, by reducing infectious complications, the present trial aims at investigating the underlying carbohydrate and protein metabolism changes, as well as the immune and inflammatory modulations associated with this improvement.

Enrollment on day 3 of critically ill patients, without contraindication to EN, not achieving 60% of the ICU per protocol energy target.

Intervention: Randomization to either continued pure EN, or from day 4 to supplemental PN to complete EN at target validated by indirect calorimetry.

Measurements: Indirect calorimetry on Days 3, 4, 9 (twice). Primary endpoints = glucose and leucine metabolism On days 4 and 9-10: isotopic investigation of glucose metabolism, and immune and inflammatory responses// Day 9-10: isotopic investigation of protein (leucine) metabolism Secondary endpoints: Insulin requirements, area under the curve (AUC) of blood Glucose, infections after day 9, overall complications, length of mechanical ventilation, of ICU and hospital stay.

Inclusion Criteria:

• estimated duration of ICU stay > 5 days,
• estimated survival > 7 days,
• absence of contraindication to EN
• need for mechanical ventilation
• informed consent obtained from patients, close relative, or referring physician

Exclusion Criteria:

• refusal of the patient or of the next of kin
• age < 18 years
• non-functional digestive tract (short bowel, persistent ileus, proximal intestinal fistula high rate > 1.5 litres/day)
• already receiving PN before Day 3
• absence of a central venous catheter
• women who are pregnant (pregnancy test).
• Admission after cardiac arrest, or severe brain injury