EE: Duration of Measurement (Steady State) (2013)


McClave SA, Spain DA, Skolnick JL, Lowen CC, Kieber MJ, Wickerham PS, Vogt JR, Looney SW. Achievement of steady state optimizes results when performing indirect calorimetry. JPEN J Parenter Enteral Nutr. 2003; 27(1): 16-20.

PubMed ID: 12549593
Study Design:
Time Study
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
  • Evaluate the necessity and significance of achieving steady state as compared to simple interval testing
  • To determine the optimal steady state criteria that would best correlate to the 24-hour total energy expenditure
  • To help identify those patients who might need 24-hour indirect calorimetry testing.
Inclusion Criteria:
  • Hemodynamically stable and in a plateau phase of their ventilatory support, with the anticipation that ventilator settings would not be changed during the ensuing 24-hour period
  • Patient with respiratory failure on mechanical ventilation (i.e., hospitalized).
Exclusion Criteria:
  • Evidence of medical or surgical instability
  • Demonstration of a measured RQ out of physiological range
  • Conditions that may have prohibited IC testing such as poor cooperation, fraction of inspired O2 higher than 0.80 or a positive end-expiratory pressure (PEEP) 20mm Hg or higher.
Description of Study Protocol:


Sample comprised of hospital patients on mechanical ventilation.


Time series.

Statistical Analysis

  • Pearson correlation coefficient calculated between seven snapshots (three steady-state periods and four time intervals) REE and the total energy expenditure (TEE) for each subject
  • Steiger's methods used to determine whether the correlations of different snapshots with TEE were significantly different from each other
  • Paired T-tests were used to compare the mean REE for each snapshot with the mean TEE.
Data Collection Summary:

Timing of Measurements

  • REE obtained and averaged each minute for the initial hour (to simulate routine snapshot IC testing)
  • Then obtained every 15 minutes for the remaining 23 hours of the study.

Dependent Variables

  • Total Energy Expenditure (TEE): Cumulative energy expenditure derived for the entire 24 hours by measuring VO2:VCO2 the first 60 minutes and then every 15 minutes for the remaining 23 hours
  • Measured REE: [(VO2, L per minute), VCO2 (L per minute; ml per kg per minute), RQ, ventilation (L per minute)], Coefficient of Variation (CV) (optimal prediction of REE by steady state criteria):
    • IC type: Nellcor Puritan Bennett 7250 Indirect Calorimeter
    • Equipment of calibration: Not mentioned
    • Coefficient of variation using std gases: Yes, over the first 30 minutes of the study
    • Rest before measure (state length of time rested if available): Resting throughout
    • Measurement length: One minute
    • Steady state: See middle column
    • Fasting length: Patients receiving nutrition support by the enteral or parenteral route were fed by continuous infusion throughout the study
    • Exercise restrictions XX hour prior to test? NA
    • Room temperature: Not mentioned
    • Number of measures within the measurement period: 15
    • Were some measures eliminated? Based on study design
    • Were a set of measurements averaged? Yes
    • If average, identify length of each measure and number of measurements? The first 15 one-minute measurements and then each hour after
    • Coefficient of variation in subjects measures? Divided into two groups (9.0 or less and more than 9.0 in the first 30 minutes)
    • Training of measurer? Not mentioned
    • Subject training of measuring process? Not mentioned
    • RQ: The ratio of VCO2/VO2 and was calculated by the monitor
    • Monitored heart rate? Unknown
    • Body temperature? Unknown
    • Medications administered? Unknown
    • Sleep or rest: Yes, measured during
    • Physical activity: Not necessary
    • Food intake: Continuous enteral feeding was provided for 77.4% of patients, continuous TPN in 13.6%; continuous nutrition support by both routes in 4.5%; no nutrition therapy in 4.5%.

Independent Variables

  • Three steady state (SS) periods for consecutive five-minute periods:
    • SS10: VO2:VCO2 change by 10% or less
    • SS15: VO2:VCO2 change by 15% or less
    • SS20: VO2:VCO2 change by 20% or less
  • Four separate time intervals defined by initial consecutive timed intervals:
    • INT20: Initial 20 minutes
    • INT30: Initial 30 minutes
    • INT40: Initial 40 minutes
    • INT60: Initial 60 minutes.
Description of Actual Data Sample:
  • Initial N: N= 25 patients
  • Final N: N=22  (59% male, N=13; 41% female, N=9); three patients were excluded from analysis for failure to obtain a full 24 hours of IC data; APACHE III score, mean 42.0 with a range 12 to 77)
  • Age: Mean age 52.8 y (range, 16 to 84)
  • Location: Louisville, Kentucky.
Summary of Results:

Individual Characteristics

  • Circulatory hormones: Not mentioned
  • Breathing ability: All were on ventilatory support
  • Medical tests and procedures: Measurements occurred during any tests and procedures but were not reported
  • Chemicals (medications, drugs and herbs; caffeine; nicotine; alcohol): Medications given and measurements taken but not reported. 

Measurement Results

  • Mean 24-hour total energy expenditure (TEE) for all study patients: 1,999 (+90) kcal per day
  • Mean 24-hour total energy expenditure (TEE) for study patients with low variation in VO2 (CV less than 9.0): 2,142 (+118) kcal per day
  • Mean 24-hour total energy expenditure (TEE) for study patients with high variation in VO2 (CV more than 9.0): 1,857 (+125) kcal per day
  • Mean CV = 15.0 (±1.7)
  • 16 of 22 achieved steady state of VO2:VCO2 change by 10% or less. 

Correlation Between REE Values of Short-term Steady State and Interval Periods to Mean 24-hour TEE:

  • The mean REE for all steady state definitions and interval periods correlated significantly with the 24-hour TEE with no significant difference in means by paired T-tests
  • The actual value obtained for the REE +10% for all steady state and interval periods was significantly different from the 24-hour TEE (P<0.05 by paired T-test)
  • The best correlation to 24-hour TEE was observed when the mean REE was obtained from the steady-state period defined by the most stringent criteria (five minutes with VO2:VCO2 change 10.0% or less; R=0.943)
  • Correlation to 24-hour TEE diminished as less stringent criteria for the steady-state interval was used. . .with a significant decrease in correlation when comparing the most stringent criteria (10% or less change) with 20% or less change (R=0.943 vs. R=0.817, P<0.001)
  • Similar correlation to 24-hour TEE was obtained for the mean REE from the initial 60-minute interval (INT60; R=0.942 vs. R=0.929, P=0.329). Shortening the interval testing to 40 minutes or less yielded significant decreases in correlation with TEE (R=0.929 INT60; R=0.838 for INT40, R=0.868 for INT30, R=0.838 for INT20).

The Effect of Gas Exchange Parameters and Correlation with REE Values and Mean 24-hour TEE were Measured

  • In a patient population with CV less than 9.0 in the first 30 minutes, the correlation (R-value) with TEE (mean CV=4.9±0.4) decreases when the steady state criteria is less stringent
  • The mean REE obtained from almost any interval (INT20, INT30, INT40) resulted in similar correlation (R>0.920, P<0.001)
  • In a patient population with CV higher than 9.0 in the first 30 minutes, the correlation with TEE (mean CV=15.0±1.7) decreases with shortening the interval testing (R=0.937, 0.795, 0.788, 0.729) and with less stringent steady state criteria (0.960, 0.917, 0.772)
  • In patients with high variation, only the mean REE with 60-minute interval had similar correlation with the 24-hour TEE (R=0.960 vs. R=0.937, P=0.212)
  • The definitions of steady-state criteria and use of short-term interval testing become more clinically important in those patients with greater physiologic variation and high CV values for VO2
  • In a subset of patients with low variation (CV of 9.0 or less), the best correlation was still seen with the SS10 period of most stringent criteria (R=0.942), but the mean REE obtained from almost any interval (INT20, INT30, INT40) resulted in similar correlation (R≥0.920, P<0.001) for all comparisons:
    • Mean REE for less stringent steady-state periods (SS15, SS20) resulted in decreasing degrees of correlation, with a significant decrease in correlation when comparing with the most stringent criterion [less than 10% change with less than 20% change (R=0.942 vs. R=0.831, P=0.22)]
  • Of note, variation in gas parameters could not be anticipated by the mean APACHE III score; i.e., APACHE mean score was significantly higher in those patients with a low CV compared to patients with higher CV (47.1±7.1 vs. 37.4±5.7, P=0.002).
Author Conclusion:
  • Results of the current study with 1,328 data point per patient support the clinical importance of achieving steady state when performing IC testing. The average REE for the steady-state period defined by the most stringent criteria (i.e., steady state of five minutes with 10% or less coefficient of variation) correlated best to the measured 24-hour TEE, regardless of the variation in gas exchange parameters. This steady-state REE vs. superior to that REE obtained by any interval testing up to and including 60 minutes in duration.
  • Previous findings suggest factors such as severity of illness, circadian rhythm, sedation, nutrition therapy, nursing care, motor activity and pain often lead to alteration in energy expenditure, resulting from clinical fluctuations in the physiologic state. A snapshot REE may vary 10% to 23% above a single measured snapshot REE.
  • Although these study results standardize the methodology, the statistical differences between the various steady-state and interval criteria do no necessarily represent clinically important differences
  • Steady state should be defined by change in VO2 and VCO2 of less than 10% over a period of five consecutive minutes. IC testing may be terminated when the patient achieves this steady state. The values for the mean REE from this steady-state period, with no further adjustments (in the absence of fever), can be used as an accurate representation of the 24-hour TEE. For the patient who fails to achieve steady state and is metabolically unstable, more prolonged testing is required (minimum of 60 minutes) and 24-hour IC monitoring should be considered.
Funding Source:
University/Hospital: Louisville School of Medicine, Stanford University, Kindred Healthcare
Reviewer Comments:


Well-designed study and generalizable to adults in critical care on ventilatory support that do not experience artifactual errors (i.e., variability caused by change in inspired oxygen or leaks). 


  • Questionable validity of indirect calorimeter
  • Did not describe IC methods of machine calibration, training of measurer and if a thermoneutral environment; of note, the brand name of the machine is known to self-calibrate with measurements
  • Did not explain why subjects were unable to obtain 24-hour data
  • Did not identify ethnicity or weight of subjects
  • An intervening variable not measured was mentioning the initial start time (i.e., time of day when first 30 minutes placed in a high or low CV
  • Of interest would have been important to identify medications altering metabolism and changes related to enteral or parenteral nutrition.
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? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  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? Yes
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  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? Yes
  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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  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? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  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? Yes
  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? ???
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.7. Were the measurements conducted consistently across groups? Yes
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? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  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? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes