Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  1. Evaluate the necessity and significance of achieving steady state as compared to simple interval testing
  2. To determine the optimal steady state criteria that would best correlate to the 24 hr total energy expenditure
  3. To help identify those patients who might need 24-h indirect calorimetry testing


  • Steady state
  • RQ: The ratio of VCO2 VO2and was calculated by the monitor
  • Total energy expenditure: The cumulative energy expenditure derived for the entire 24 hr by the 7250 IC monitor
Inclusion Criteria:
  1. Hemodynamically stable and in a plateau phase of their ventilatory support
  2. Pt with respiratory failure on mechanical ventilation (i.e., hospitalized)
  3. Medications allowed
Exclusion Criteria:
  1. Evidence of medical/surgical instability
  2. Demonstration of a measured RQ out of physiological range
  3. Conditions that may have prohibited IC testing such as poor cooperation, fraction of inspired O2>0.80, or a positive end-expiratory pressure (PEEP) >20 mm Hg
Description of Study Protocol:


  • Ht measured? No
  • Wt measured? No
  • Fat-free mass measured? No


  • Monitored heart rate? Unknown
  • Body temperature? unknown
  • Medications administered? Unknown

Resting energy expenditure

  • IC type: Nellcor Puritan Bennett 7250 Indirect Calorimeter
  • Equipment of Calibration: Not mentioned
  • Coefficient of variation using std gases: Yes; over the first 30 min of the study;
  • Rest before measure (state length of time rested if available): Resting throughout
  • Measurement length: 1 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 hr prior to test? NA
  • Room temp: Not mentioned
  • No. of measures within the measurement period: 15
  • Were some measures eliminated? Based on study design
  • Were a set of measurements averaged? Yes
  • IF avg, identify length of each measure & no. of measurements? The first 15 1-minute measurements and then each hour after
  • Coefficient of variation in subjects measures? Divided into 2 grp: =9.0 and >9.0 in the first 30 mins
  • Training of measurer? Not mentioned
  • Subject training of measuring process? Not mentioned
Data Collection Summary:

Outcome(s) and other measures

  1. Measured REE [(VO2 l/min), VCO2 (l/min; ml/kg/min), RQ, ventilation (l/min)], Coefficient of Variation (CV)
  2. Total Energy Expenditure (TEE) by measuring VO2 VCO2the first 60 minutes and then every 15 min for the remaining 23 hrs

Blinding used: No

Description of Actual Data Sample:
  • N=25 patients
  • N=22 pt completing the study
  • Mean age: 52.8 y (Range 16-84)
  • N=13 (59%) males; N=9 (41%) females
  • APACHE III score for males: mean 42.0 with the range 12-77).
  • 100% on mechanical ventilation
  • Setting: 14 (63.6% in short-term acute care unit)
  • 3 patients excluded from analysis for failure tObtain a full 24 hours of IC data

Statistical tests

Pearson correlation coefficient b/t the “snapshot” REE value and the TEE value for each subject was calculated. Steiger’s method was used to determine whether the correlations of different “snapshots” with the TEE were significantly different from each other. Paired t tests were used to compare the mean REE for each “snapshot” with the mean TEE.

Summary of Results:


Number of measurements: 1328 data points on each patient; VO2and VCO2and REE were obtained and averaged each minute for the initial hour, and then every 15 min for the remaining 23 hr.

Length of measurements

  • INT20=Initial 20 min
  • INT30=Initial 30 min
  • INT40=Initial 40 min
  • INT60=Initial 60 min

Steady state

  • SS10=VO2VCO2change =10%
  • SS15=VO2VCO2change =15%
  • SS20=VO2VCO2change =20%
  • RQ=Excluded if out of physiologic range


  • Sleep or rest: Yes measured during
  • Physical activity: Not necessary
  • Food intake: Continuous enteral fdg was provided for 77.4% pt, continuous TPN in 13.6%; Continuous nutrition support by both routes in 4.5%; no nutrition therapy in 4.5%
  • Various times in the day:


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


  • Mean 24-h total energy expenditure (TEE)for all study patients: 1999 (+90) kcal/d
  • Mean 24-h total energy expenditure (TEE)for study patients with low variation in VO2 (CV<9.0): 2142 (+118) kcal/d
  • Mean 24-h total energy expenditure (TEE)for study patients with high variation in VO2 (CV>9.0: 1857 (+125) kcal/d; mean CV=15.0 (±1.7)
  • 16 of 22 achieved steady state of VO2VCO2change by =10%.

Correlation between REE values of short-term steady state and interval periods to mean 24-hr 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-hr 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 (5 min with steady state =9.0%; R=0.943).

Correlation to 24-hr 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% change) with <20% 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 min interval (INT 60; R=0.942 vs R=0.929, p=0.329). Shortening the interval testing to 40 mins 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 INT 20)

The effect of gas exchange parameters and correlation with REE values and mean 24-hr TEE were measured

In a pt population with CV<9.0 in the first 30 min, 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 (INT 20, INT 30, INT 40) resulted in similar correlation (R>0.920, p<0.001)

In a pt population with CV >9.0 in the first 30 min, 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 RE with 60 minute interval had similar correlation with the 24 hr TEE (R=0.960 vs. R=0.937, p=0.212); Of note, variation in gas parameters could not be anticipated by the mean APACHE III score; ie., APACHE mean score was significantly higher in those pt with a low CV compared to pt with higher CV (47.1±7.1 vs. 37.4±5.7, p=0.002).

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

Author Conclusion:

As stated by the author in body of report:

  • Results of the current study with 1328 data points 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 5 minutes with =10% coefficient of variation) correlated best to the measured 24-hr TEE, regardless of the variation in gas exchange parameters… this steady-state REE was superior to that REE obtained by any interval testing up to and including 60 mins 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 “snap-shot” 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 <10% over a period of 5 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 mins) 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.”


  • “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 tObtain 24 h 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 meds altering metabolism and changes related to enteral/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? 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? 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? 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? Yes
  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? 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%.) 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? Yes
  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