EE: Diurnal Variation (2013)


Frankenfield DC, Wiles II CE, Bagley S, Siegel JH. Relationships between resting and total energy expenditure in injured and septic patients.  Crit Care Med. 1994;22(11):1796-1804.

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

To determine the difference between total energy expenditure (TEE) and resting energy expenditure (REE) in a group of trauma patients and a group of septic patients with multiple organ dysfunction.


  • “Steady state” - not defined
Inclusion Criteria:

Trauma Group

  1. Understand and give written consent from a family member.
  2. Admitted within 3 d of a blunt or penetrating injury with minimum Injury Severity Score (2) of 16.
  3. Mechanically ventilated.
  4. FIO2 < 0.8
  5. No air leaks in the ventilatory circuit
  6. Expected to require parenteral nutrition
  7. Not receiving ethanol for prophylaxis of delirium tremens

Septic Group

  1. Understand and given written consent from a family member.
    • In addition to trauma groups criteria, this septic group had to meet the following conditions:
  2. Documented or presumed infection:
    1. Leukocyte counts of >11,000 cells/mm2/L;
    2. Body temperature of >38.3 °C;
    3. Documented source of infection or deterioration in clinical course mandating immediate antibiotic therapy.
  3. Hyperdynamic response:
    1. Heart rate of >90 beats/min;
    2. Cardiac index of >5.0 L/min/m2 and either systemic vascular resistance index of <1100 dyne-sec/cm5.m2 or oxygen consumption index >200 mL/min/m2
  4. Dysfuction of at least 2 organ systems:
    1. Respiratory—mechanically ventilation required;
    2. Cardiovascular—inotropic support to maintain oxygen delivery of >/= 600mL/min/m2;
    3. Renal—dialysis required for fluid and azotemia control;
    4. Hepatic—total bilirubin concentration of > 2.5 mg/dL serum albumin of 2.8 g/dL;
    5. Gastrointestinal—failure to tolerate tube feedings or gastric drainage of >800 mL/day with distended abdomen;
    6. Coagulation—platelet count of <60,000 platelets/mm3 or platelet infusion required.
Exclusion Criteria:
  1. Refusal to consent
  2. Not meeting inclusion criteria
  3. Diabetes or other preexisting metabolic disorders
Description of Study Protocol:

An indirect calorimeter was used to measure energy expenditure at rest (REE) 0700 and 1900 hrs. The energy expenditure measurement was then continued for up to 12 hrs (TEE)

2 comparisons were generated: a) 1 12-hr TEE with a controlled 20min-REE and b) a 12-hr TEE trend measurement during which generally more patient activity occurred (0700 to 1900) with a 12-hr TEE trend measurements during which less patient activity occurred (1900 go 0700). 

Data were collected for a maximum of 10 days per subject.


  • Ht measured? yes
  • Wt measured? yes
  • Fat-free mass measured? No
  • Others: % ideal body wt, adjusted wt (ABW), body surface area(BSA)


Clinical data was collected for computation of an illness severity score: blood gas analysis, electrolyte values, metabolic profiles, hematology and coagulation studies, ventilator settings, body temperature, cardiovascular and hemodynamic variables, sedative, narcotic, and inotropic drug administration

Resting energy expenditure

  • IC type: Deltatrac MB100
  • Equipment of Calibration: yes
  • Coefficient of variation using std gases: not reported
  • Rest before measure (state length of time rested if available): not specified
  • Measurement length: 15-25 mins for REE; 12 hrs for TEE
  • Steady state: not reported
  • Fasting length: Not reported
  • Exercise restrictions XX hr prior to test? not applicable
  • Room temp: not reported
  • No. of measures within the measurement period: Continuous
  • Were some measures eliminated? Yes, a microprocessor in the metabolic monitor automatically discard all outlying data
  • Were a set of measurements averaged? Not reported
  • Coefficient of variation in subjects measures? No
  • Training of measurer? Not reported
  • Subject training of measuring process? Not reported



  • Intervening factor:
Data Collection Summary:

Outcome(s) and other measures

  1. Measured REE [(VO2, l/min), VCO2 (l/min; ml/kg/min), RQ, ventilation (l/min)].
  2. Predicted RME using HB
  3. Metabolically active wt was calculated for obese subjects from actual and ideal body wt.
  4. Body surface area were calculated
  5. Independent variables of weight, height, age

Blinding used: no

Description of Actual Data Sample:

Total 33 patients

  • 13 trauma patients
    • 10 M; 3 F
    • Mean age, y: 28±9
  • 20 septic patients
    • 17M; 3F
    • Mean age, y: 32±11

Statistical tests

  • The REE/TEE pairs were tested by Student’s paired t-test
  • Difference between the trauma and septic groups and between day and night TEE were tested with Student’s independent t-test.  Significant was set at p<.05
Summary of Results:

Descriptive (mean ±SD)

Trauma Sepsis
Ht,cm 178±61 177±6
Wt,kg 75±18 83±17
%IBW 102±10 112±21
ABW 75±13 78±9
BSA 1.92±0.19 1.99±0.18


Septic subjects had a significant higher REE and TEE than trauma subjects. Mean REE was within 5% of mean TEE in both the trauma and septic groups. The difference between REE and TEE was statistically significant.  The ratio of REE to TEE ranged from 0.67 to 1.21.  In 10 (11.6%) of 86 trauma and 17 (11.0%) of 154 septic studies, REE exceeded TEE by more than the IC measurement error of 4%.

Diurnal Variation

TEE measured over the night hours (1900 to 0700) was not significantly different from TEE measured over the day hours (0700 to 1900).  REE at 0700 did not differ from REE at 1900 hrs.

0700REE 2753±355 3365±556
1900REE 2755±446 3442±691
Day TEE 2815±412 3570±691
Night TEE 2867±392 3475±551

Changes in REE/TEE Over Time

In 9 (69%) of 13 trauma subjects and 13 (65%) of 20 septic subjects, EE was measured for 4 days.  Comparing day 0,2,4, there was no significant changes in mean REE or TEE in both groups. However, individual difference ranged from 34 to 1424 kcal/day (i.e. up to 50% of initial measurement of REE)

In a subset of subjects (3 trauma and 9 septic patients), data were collected for 7 days. Neither mean REE nor mean TEE was significantly changed on day 7 compared with day 0. However, there was wide individual variation

Effects of Sedation and Neuromuscular Blockade in REE/TEE

All subjects received sedative medication, so an analysis of the difference between REE and TEE in sedated vs. nonsedated subjects could not be performed.

In the septic group, 42% of studies were performed during neuromuscular blockade plus sedation. Both REE and TEE were significantly higher in the medically paralyzed group than in the nonparalyzed group (about 120 kcal/day).

TEE was greater than REE in both the medically paralyzed and nonparalyzed studies.  There was a positive correlation between neuromuscular blocker dose (r2=.31) and TEE (r2=.32).


  • Number of measurements
    • REE: minimum of 15 valid measurements
    • TEE: continuous measurements for up to 10 days.
  • Length of measurements
    • REE: 15-25 min
    • TEE: 12 hrs
  • Steady state: Not specified
  • RQ: Not specified


  • Sleep or rest: Pt was not to be disturbed
  • Physical activity: None
  • Food intake: NPO; parenteral nutrition solutions were administered via continuous drip, and were not interrupted for the REE test
  • Various times in the day:
    • REE at 0700 and 1899
    • TEE from 0700 to 1900 (day)
    • TEE from 1900 and 0700 (night)


  • Circulatory hormones: Not reported
  • Breathing ability: all patients were mechanically ventilated
  • Medical tests/procedures: No major procedures were performed within 15 mins of the test
  • Chemicals (medications/drugs/herbs, caffeine, nicotine, alcohol): Morphine and fentanyl was infused during 99% of studies.  Neuromuscular blocking agents were used in 42% of septic studies.
Author Conclusion:

“In the current study, trauma and septic patients were markedly hypermetabolic, despite heavy sedation and in many cases medical paralysis. Additionally, a 20-min measurement of REE approximated a 12-hr measurement of TEE.  Mean REE/TEE of the groups were stable over several days of study, but there was wide individual variation.”

“REE in current study was 1.55 x predicted basal expenditure for trauma and 1.91 x predicted basal energy expenditure for sepsis.”

“REE generally approximated TEE in the current study, and both REE and TEE were significantly increased above predicted basal energy expenditure. In the current study, mean TEE (3273±647 kcal/day) was 1.037 x REE.”

“Although more activity occurs in the ICU during the day, TEE from 0700 to 1900 was not different from TEE measured from 1900 to 0700 hrs.”

“The frequency rate of REE exceeding TEE by more than the IC measurement error was ~11%). 3 types of errors were noted:

  1. TEE decreased in relation to prior and subsequent TEE periods while REE remained stable (23% of trauma; 1.3% of septic)
  2. TEE was stable but REE increased compared with prior measurements. Both TEE and REE remained elevated in subsequent study periods, with TEE greater than REE (3.4 % of trauma; 4.5% of septic)
  3. REE increased in relation to prior and subsequent values of REE, while TEE remained stable (5.7% of trauma; 4.5% of septic).”

“Error type “a” cannot be explained, but since the decrease in TEE was transient (<12 hrs), the use of REE estimate TEE remains valid. Error type “b” seems to be not an error, but an actual physiologic change in metabolic rate that persisted into subsequent study periods. Error type “c” can be interpreted as an attempt to measure REE in patient who was not at rest.  It is the most significant error, because incorrect perception will be given of TEE leading to overfeeding. Although the rate of error type “c” is low, its occurrence is undetectable.”

“In subjects who remained in the study for at least 4 days, mean REE and TEE were stable from day 0 to day 2 to day 4.  Mean difference seemed clinically insignificant, but individual variation was wide (up to 50% from values recorded on day 1 of study), indicating that in individual patients, the difference in REE and TEE from day to day can be significantly significant. In patients who remained in the study for at least 7 days, there was no significant fluctuation in mean REE or TEE from day 0 to day 7, but again individual variation was great.”

“Although EE is stable for at least a week in population of trauma and septic patients, daily variation of EE in individual patients may be clinically significant, requiring frequent measurement by indirect calorimetry.  In most cases, a 20-min measurement of REE will be sufficient to assess TEE for the patients while the condition of severe stress and heavy sedation persist.”
Funding Source:
Reviewer Comments:


  • Inclusion/exclusion criteria are clear. Limit the possible confounding factors that might influence the IC results.
  • Assess the effects of the sedation/medication on TEE/REE measurements.
  • Great study design with appropriate statistics
  • Addressed and discussed 3 types of errors of the situation when REE >TEE by more than the IC measurement error (the rate was ~ 11%)
  • Conclusions were made in consideration to the daily variation in TEE/REE on individual basis, even though the mean TEE/REE (group variance) was stable for at least a week.


  • Results only applied to trauma and septic patients who are sedated, mechanically ventilated and on parenteral nutrition.
  • Septic subjects seemed to weigh higher than trauma group (according to the descriptive data). Did not test or report if weight difference between groups was significant or not. Plus, weight status was not adjusted in the statistic analysis. Question if consistent higher REE/TEE in septic group is related to weight? (a possible confounder)
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? 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? 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