EE: Stable, Acute Care Patients (2005)


Heymsfield SB, Hill JO, Evert M, Casper K, DiGirolamo M. Energy expenditure during continuous intragastric infusion of fuel. Am J Clin Nutr 1987;45:526-33.

Study Design:
Non-Randomized Controlled Trial
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To define the effects of three levels of continuous intragastric-formula infusion on resting metabolic rate.


  • Steady state – not defined
  • Submaintenance formula – 1.02±0.04 times the fasting metabolic rate
  • Maintenance formula – 1.39±0.01 times the fasting metabolic rate
  • Supramaintenance formula – 2.77±0.2 times the fasting metabolic rate
Inclusion Criteria:
  1. Healthy volunteers
  2. Taking no medications
  3. No prior hx significant weight loss.
Exclusion Criteria:
None listed
Description of Study Protocol:

Subjects were admitted to the Clinical Research Facility of Emory University MC and began fasting after 8 pm on the day of admission. Beginning at 8 am the following day, fasting metabolic rate was measured by IC. A total of between 5 and 8 measurements were performed on each subject. After the initital measurements of fasting energy expenditure were completed, subjects were free to move about and eat a regular hospital meal at noon. That evening a thin nasoenteric tube was inserted and an intragastric infusion of formula was started. Group 1, the submaintenace group, (n=6) received an infusion rate approximately equal to their fasting energy expenditure (0.9-1.1 X FMR). Group 2, the maintenance group,  (n=19) received a formula approximately aimed at producing estimated zero energy balance (1.3-1.5 X FMR). Intraprandial metabolic rate was then measured at about 1 h intervals throughout the following day, and the 5 – 8 measurements were averaged on each subject. 14 of the Group 2 members went on to become Group 3, the supramaintenance group, who received a feeding for an additional day that was equal to 2.6 – 3 X FMR. An additional 5 – 8 measurements were made and averaged through that second day.


  • Ht measured? yes
  • Wt measured? yes
  • Fat-free mass measured? no
  • BMI measured? Yes


  • Monitored heart rate? no
  • Body temperature? no
  • Medications administered? no

Resting energy expenditure

  • IC type: Subjects breathed through a face mask   Expired air was captured in a meteorological balloon. Minute ventilation rate was measured by a digital pneumontachograph (VR-1 Accutach, McGaw) and expired gas was analyzed using Applied Electrochemistry (Sunnyvale, CA) oxygen (S-3A) and CO2 (CD-3A) analyzers. EE was calculated as described by Lusk.
  • Equipment of Calibration: not mentioned
  • Coefficient of variation using std gases: Not mentioned
  • Rest before measure (state length of time rested if available): 30 minutes in bed
  • Measurement length: 7-10 minutes
  • Steady state: Not mentioned
  • Fasting length: 12 hours before the first measurement only.
  • Exercise restrictions: Fasting measure taken after admission into research facility with an overnight stay;  Able to walk around facility after initial RMR measure
  • Room temperature: not mentioned
  • No. of measures within the measurement period: 5-8
  • Were some measures eliminated? No
  • Were a set of measurements averaged? Yes
  • Coefficient of variation in subjects measures? No
  • Training of measurer? Not mentioned but likely
  • Subject training of measuring process? Not mentioned


  • Enteral: Compleat Modified blenderized food source (Sandoz Nutrition, Minneapolis, MN) Caloric density 1.07 kcal/mL, energy distribution: 16% protein, 36 % fat, 48% CHO.
Data Collection Summary:

Outcome(s) and other measures

  1. Measured REE (VO2, VCO2,)
  2. Independent variables of weight, height, age, BMI, standard body weight, body surface area.

Blinding used: No

Description of Actual Data Sample:
  • N=24: 15 males, 9  females
  • Age range: 19-51 y, mean 33±1.9 y
  • Maintenance group: N=19 (13 M; 6 F).

Statistical tests

Paired t-test. Significant differences were reported if P=0.05.

Summary of Results:


N=24 Total Mean±SD      Range
Wt, kg      33.0±1.9        19-51
Ht, m         1.715±1.9
BMI          24.7±0.8       

Submaintenance group (1)

  • N=6
  • Neither average metabolic rate nor average area under the 8-h regression line differed significantly from the respective fasting value.

[Analysts note: Because sample size didn’t meet sorting criteria; evidence not used in Evidence Summary]

Maintenance group (2)

  • N=19
  • Neither average metabolic rate nor average area under the 8-h regression line differed significantly from the respective fasting value.

Supramaintenance group (3)

  • N=14
  • Average metabolic rate increased by 10.1% compared with the fasting metabolic rate (p<0.05) and by 11.7% compared with the maintenance metabolic rate (p<0.05). Likewise, the average area under the 8-h regression line increased by 10.7% during the supramaintenance formula infusion compared with the fasting metabolic rate (p<0.05) and by 9.4% compared with the maintenance metabolic rate (p<0.05).


  • Number of measurements: 5-8 per 8 h period
  • Measurement timing: 7-10 minutes
  • Physical activity: no
  • Food intake: yes
  • Various times in the day: up to once an hour between 8 am and 4 pm
  • RQ: Formula not given


  • Stability of metabolic rate during continuous infusion: The maintenance infusion CV was 6.3±0.7% (range 1.9-17.8%).

[Analyst note:  translated into individual kcal variability over 8 hours it would represent a range from 7-73 kcals/8 hours]

During the maintenance infusion, the slopes of the regression line was 0.6±0.2 kcal/h.

  • The supramaintenance infusion rate was 5.6±0.9%.  During the supramaintenance infusion, the slopes of the regression line was 0.6±0.2 kcal/h.
  • During the maintenance, and supramaintenance, the slopes were 0.7±0.2 kcal/h and 0.7±0.2 kcal/h, respectively.
  • The continuous feeding produced a relatively stable metabolic rate.    The variability in metabolic rate during continous formula infusion was always about the same or less than that seen during fasting.
Author Conclusion:

“Submaintenance and maintenance infusions were accompanied by a steady output of heat that had a variability and magnitude equal to fasting metabolic rate. Thermal losses during the supramaintenance infusion were also stable and showed little variability throughout the 1-day study period. Contrastingly, the absolute rate of heat production was significantly increased during the supramaintenance infusion relative to the metabolic rate observed during fasting and submaintenance and maintenance infusions.”

That is, “if the observations in the current report can be supported by in-depth studies, the results indicate that maintenance energy requirements are reduced during continuous feeding relative to isocaloric intermittentt food ingestion.”
Funding Source:
Government: NIH, Georgia Heart Association
Reviewer Comments:


  • Clinically relevant
  • Credible use of statistics including area under curve, intra-individual CV and slope of regression that described the relation between metabolic rate and time.


  • Limitations were not discussed.
  • Use of healthy adults with intragastric enteral nutrition would have some limitations when generalized  to ill patients.
  • Small sample size reduces power of the study.
  • Authors recognize that their hypothesis is oversimplified and needs larger studies.
  • Components of accurate IC measure criteria not specified were machine calibration, achievement of steady state in individuals and education of IC measurement process prior to initial baseline fasting RMR measure.
Analyst note:  The fasting RMR measures lasted for four hours.  In order to compare to 8-hr infusion rates, the researchers doubled the area under the 4-hour regression line for that day and then doubled.  Since the evidence analysis question looked for variability, the analyst halved the area under 8-hour fasting regression line column in Tables 2 & 3, to represent the actual data collected over 4 hours.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? N/A
  1.3. Were the target population and setting specified? N/A
2. Was the selection of study subjects/patients free from bias? No
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? N/A
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? N/A
  2.4. Were the subjects/patients a representative sample of the relevant population? N/A
3. Were study groups comparable? No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? No
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? No
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? N/A
  7.5. Was the measurement of effect at an appropriate level of precision? N/A
  7.6. Were other factors accounted for (measured) that could affect outcomes? N/A
  7.7. Were the measurements conducted consistently across groups? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? N/A
  8.2. Were correct statistical tests used and assumptions of test not violated? N/A
  8.3. Were statistics reported with levels of significance and/or confidence intervals? N/A
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  8.6. Was clinical significance as well as statistical significance reported? N/A
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? N/A
  9.2. Are biases and study limitations identified and discussed? N/A
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? N/A
  10.2. Was the study free from apparent conflict of interest? N/A