Impact of Supplemental Parenteral Nutrition in ICU Patients on Metabolic, Inflammatory and Immune Responses

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Impact of Supplemental Parenteral Nutrition (SPN) on Energy Balance, and Infection Rate in Intensive Care Patients: Underlying Metabolic, Inflammatory and Immune Mechanisms.

Conditions
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Critical Illness

Intervention / Treatment
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* Dietary Supplement: Supplemental parenteral nutrition (SPN)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Enteral nutrition only<br>Enteral nutrition to be progressed as soon as possible to energy target measured on day 3, and verified on day 4, using the usual facilitators (prokinetics) | |
| Experimental: Supplemental parenteral nutrition<br>Addition of supplemental parenteral nutrition to complete the gap between energy delivered by enteral feeding and energy target measured on day 4. Aim: 100% of this target, and not exceeding it, no catch up for energy deficit accumulated before day 4. | Dietary Supplement: Supplemental parenteral nutrition (SPN)<br>* The amount of energy delivered by SPN will depend on the indirect calorimetry measurement and actual enteral feed delivery. SPN will be reduced with progressing EN<br>* Other names: Standard industrial PN solutions;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose and Leucine turnover | On D04:Infusion after priming of 6.6 2H2 glucose and NaH13CO3 On Day 09-10: Infusion after priming of NaH13CO3 and of L-[1-13C]-Leucine + repeat of the glucose sequence | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune and inflammatory impact of optimized target feeding | lymphocyte phenotypes: lymphocyte subpopulations (frequency), level of activation (CD69), memory markers, effectors, regulators Cluster differentiation CD4, CD8, and natural killer (NK) phenotypes Cell inflammatory response (WBA and PBMC) on D4 and D10±1: IL-2, TNF-α, interleukine-6 (IL-6), IL-1, TGF, IL-10, in culture for 24 to 48h ex vivo and post stimulation by memory mix and mitogens. Serological inflammatory response (WBA and PBMC) on D4 and D10+1: TNF-α , IL-6, C-reactive protein (CRP): ex vivo with ELISA Nosocomial infections after day 8 | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Energy requirements, Glucose turnover, Protein turnover