New Stable Isotope Method to Determine Protein Requirements in Critically Ill Children

Development of New Stable Isotope Method to Determine Protein Requirements in Critically Ill Children

The need for certain components of food (i.e. protein) for critically ill children is not clear. It is important to have critically ill children fed adequately to prevent that their condition becomes worse or that recovery takes longer. Research methods used in the past to investigate the need for protein (Nitrogen Balance calculations), were not sensitive enough in severely ill children. The purpose of this study is to develop a new research method to determine the need for protein in severely ill children. In order to develop this new method, more information is needed on the way the body of these children uses protein in 24-hours. In the present study during 24-hours 8 children of age less than 18 years who are admitted to either the Pediatric ICU or the Cardiovascular ICU. Subjects will receive a standard nutrition, providing an age specific amount of protein (age ≤ 3: 2.52 protein g/kg BW.d; age 4-6: 1.8 protein g/kg BW.d; age > 10: 1.44 protein g/kg BW.d) via tube feeding. They will also receive a mixture of stable isotopes of amino to investigate protein behavior in the body (protein kinetics) both by infusion in their blood and together with the nutrition. Blood will be drawn every 60 minutes during the 24-hour period and the behavior of protein and the concentrations in blood of amino acids and urea will be measured. Urine will be collected to measure nitrogen balance. The investigators will compare the results of this nitrogen balance method with the results of the stable isotope method. PIM2, PRISM, SIRS criteria will be used to get information on the severity of illness of the subjects. Also body weight and length as well as body composition of the subjects will be measured at the start and after the 24-hour period. Body composition will be measured by Bioelectrical Impedance Spectroscopy. Endpoints of the study are net whole-body protein synthesis (protein balance), 24-hour pattern of protein balance, 24-hour urea production, 24-hour nitrogen balance, 24-hour contribution of arginine kinetics to whole body protein breakdown, 24-hour muscle protein breakdown, splanchnic amino acid extraction and plasma amino acid concentrations.

Study Overview

• Status: Completed
• Conditions: Critically Ill

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Stable critically ill children admitted to the Pediatric Intensive Care Unit or Cardiovascular Intensive Care Unit of ACH

Description

Inclusion Criteria:

1. Critically ill children with age less than 18 years at the time of enrollment
2. Admitted to the Pediatric ICU or Cardiovascular ICU, with an expected stay of >72 hours
3. One arterial line (or umbilical arterial line) and one multi-lumen central venous line (or two peripheral venous catheters) in place.
4. Continuous total parenteral nutrition or continuous enteral feeding (e.g. via nasogastric, nasoduodenal, gastric, jejunal tube) with standard nutrition appropriate for age and weight expected during admission.
5. No planned major changes or interventions (such as surgery) in the treatment and care of the patient from enrollment to completion of study period (end of 24-hour stable isotope infusion protocol).
6. Hemodynamic stable condition (with or without continuous inotropic medication) defined as ≤1 boluses of volume resuscitation for hypotension in 24 hour.
7. No significant loss of plasma/blood from wounds or drains, that may influence the results of the study, no chylothorax.
8. Informed consent by parent(s) or LAR.

Exclusion Criteria:

1. Congenital/acquired metabolic or endocrine disorders or hepatic or renal failure or anuria or oliguria.
2. Gastrointestinal obstructions or any condition that causes malabsorption.
3. Active gastro-intestinal bleeding.
4. Fluid restriction (<100 ml/kg BW.day) making administration of intravenous and enteral stable isotopes impossible.
5. Any other condition that according to the Principal Investigator or study physician would interfere with collecting study samples (for example isolation due to MRSA infection).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Standard clinical care; Standard nutritional therapy and treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole body protein synthesis rate	Whole body protein synthesis rate in the fed state	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole body protein breakdown rate	Whole body protein breakdown rate in the fed state	24 hours
Whole body protein breakdown rate	Whole body myofibrillar protein breakdown rate in the fed state	24 hours
Whole body Arginine production rate	Net whole body arginine production rate in the fed state	24 h
Splanchnic amino acid extraction	Splanchnic amino acid extraction in the fed state	24 hr
Urea production	Whole body urea production in the fed state	24 hr
Plasma amino acid levels	Plasme amino acid level in the fed state	24 hr

Collaborators and Investigators

• Sponsor: Texas A&M University
• Collaborators: Arkansas Children's Hospital Research Institute
• Investigators: Principal Investigator: Marielle P Engelen, PhD, University of Arkansas

Publications and helpful links

General Publications

• de Betue CTI, Garcia Casal XC, van Waardenburg DA, Schexnayder SM, Joosten KFM, Deutz NEP, Engelen MPKJ. 24-Hour protein, arginine and citrulline metabolism in fed critically ill children - A stable isotope tracer study. Clin Nutr. 2017 Jun;36(3):876-887. doi: 10.1016/j.clnu.2016.12.023. Epub 2017 Jan 4.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: January 12, 2012
• First Submitted That Met QC Criteria: January 17, 2012
• First Posted (Estimate): January 18, 2012

Study Record Updates

• Last Update Posted (Actual): October 11, 2017
• Last Update Submitted That Met QC Criteria: October 10, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: ICU; critically ill children; stable isotopes; 24hr protein balance; fed state
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: 101653