This study will use the indicator amino acid oxidation technique (IAAO) to determine protein oxidation of ICU patients at two protein intakes: 1.3 g/kg/d versus 2.0 g/kg/d.

Rationale:

While protein administration guidelines for critical care are available from international organizations such as ASPEN and ESPEN, they vary greatly in their recommended dose and are based on relatively low-quality evidence. The Indicator Amino Acid Oxidation (IAAO) technique has been developed as a more practical and non-invasive tool to assess protein metabolism that can be used in vulnerable populations. Application of the IAAO technique in patients admitted to the Intensive Care Unit (ICU) could provide an alternative to better investigate optimal protein feeding during critical illness.

Objective:

To assess the effect of enteral feeding with higher protein content compared to standard protein content on indicator amino acid oxidation in ICU patients.

Study design:

Randomized, counterbalanced, cross-over trial.

Study population:

Adult patients with an unplanned admission to the ICU, who are mechanically ventilated and have an indication for prolonged enteral nutrition.

Intervention:

Subjects will undergo two test days in randomized order during which they receive either enteral feeding according to a standard protein dose (1.3 g/kg/d) or a higher protein dose (2.0 g/kg/d). Continuous feeding of L-[1-13C]-phenylalanine combined with breath, urine and blood samples will be applied to assess indicator amino acid oxidation.

Main study parameters/endpoints:

The primary endpoint is indicator amino acid oxidation after enteral feeding with a standard or higher protein content, determined using the Indicator Amino Acid Oxidation (IAAO) method by measuring 13CO2 enrichment in expired breath and enrichment of L-[1-13C]-phenylalanine in plasma and urine.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The overall risk of the study is negligible. The current study compares the effect of two nutritional compositions, that fall within the recommendations of international guidelines on ICU nutrition, on protein metabolism following ICU admission. To avoid overfeeding in the early phase of critical illness, both in terms of calories and protein, full enteral nutrition is provided after three days of gradual increase of intake (i.e., 25-50-75% of targeted intake, on days 1-2-3 respectively). Sampling of breath, urine, feces and plasma does not bring additional risks for this population. Our department has an extensive background in amino acid stable isotope methodology, assessment of 13CO2 enrichment in expired breath samples, and assessment of carbon dioxide production by indirect calorimetry.

Inclusion Criteria:

• ≥ 18 years old
• Unplanned admission to the ICU
• Mechanically ventilated
• Start of enteral nutrition within 2 days of intubation
• ≥ 3 days on enteral nutrition
• Expected remaining ICU stay on mechanical ventilation of ≥ 2 days

Exclusion Criteria:

• Contra-indication for enteral nutrition at the discretion of the treating physician
• Feeding intolerance during incremental feeding protocol
• Moribund or withholding of treatment
• On extracorporeal membrane oxygenation (ECMO)
• Presence of chest drains, pneumothorax, tracheoesophageal fistula or subcutaneous emphysema
• Kidney failure AND a "no dialysis"-code on admission
• Hepatic encephalopathy (West Haven criteria 3-4)
• BMI < 18 kg/m2

Study data can be made available upon reasonable request, which will be considered by the project investigators (Drs. Julia Bels, Dr. Jorn Trommelen) and the Principal Investigator (Prof. Dr. Luc van Loon). A request for data-sharing together with a developed study protocol are prerequisites for consideration.