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Essay: Compare the frequently used equations to measured REE

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Abstract
Background and Aim: ESPEN guidelines recommend to prescribe between 20 and 35 kcal/kg/day to patients requiring home parenteral nutrition. Others use predictive equations. However, these equations have not been validated. Indirect calorimetry is recommended as the gold standard method to determine energy expenditure (REE). The aim of our study was to compare the frequently used equations to measured REE.
Material and Methods: Seventy six hospitalized patients suffering from intestinal failure and aged 21 to 85 years were enrolled between January 2012 and May 2014. They were eligible for implementation of home parenteral nutrition (HPN) due to: short bowel syndrome (SBS) ‘ 54%, intestinal fistulae ‘ 24%, cancer obstruction ‘ 16%, radiation- induced intestinal injury ‘ 6%. REE measurements were compared to predictive equations by Harris and Benedict, Owen, Ireton-Jones and Mifflin, as well as ESPEN recommendations.
Results: Results: 152 calorimetry measurements (two per patients) were performed among 76 patients, after TPN administrations. An average result of REE measurement by indirect calorimetry was 1181 ?? 322 kcal/day. Variability in MEE from one measurement to the other was 8 ?? 7%. Bland Altman analysis showed a mean bias of -192 ?? 300 kcal/day between MEE and estimated energy expenditure using the HB equation which means that the equation increase the score in average by 192 ?? 300 kcal/day. Limits of agreement between the 2 methods was -780 to +396 kcal/day. Estimation energy expenditure using the Ireton-Jones equation gave a mean bias of -359 ?? 335 kcal/day. Limits of agreement between the 2 methods was -1015 to +297 kcal/day. For Owen equation, Bland Altman analysis showed a mean bias of -208 ?? 313 kcal/day and the limits of agreement between the 2 methods was -822 to +406 kcal/day. Using the Mifflin equation, estimation energy expenditure gave a mean bias of -172 ?? 312 kcal/day and the limits of agreement between the 2 methods was -784 to +439 kcal/day. Using the ESPEN range (20 to 35 kcal/kg/day) analysis showed mean bias of -13 ?? 326 kcal/day and the limits of agreement was -652 to +626 kcal/day for 20 kcal/kg/day and mean bias of -909 ?? 436 kcal/day with the limits of agreement between the 2 methods -1764 to -54 kcal/day for 35 kcal/kg/day.
Conclusion: If REE cannot be measured by IC in patients qualified for HPN, the Ireton-Jones equation and the 20 kcal/kg/day ESPEN recommendation seem to be the most appropriate ones as it provides results that constitute the best approximation of calorimetric examination results.
Key words: Resting Energy Expenditure, predictive equations, indirect calorimetry, Home Parenteral Nutrition.
1. Introduction.
Home nutrition is administered in patients who are chronically unable to take enough food via the enteral route or if such supply cannot meet their demand for energy and nutrients (1). When excessive calories are administrated, complications such as metabolic disorders and elevated liver function can be observed (2, 3). Inversely, when too little energy is prescribed, malnutrition can occur (4). Guidelines are recommending administering calorie supply in this population according to predictive equations. ESPEN, AuSPEN, BAPEN guidelines recommend to administer around 20 to 35 kcal/kg to patients suffering from intestinal failure (1, 5, 6) while ASPEN (7) or others (8) propose 25 kcal/kg/day or 2000 kcal/day. Some clinicians use predictive equations such as Harris Benedict (9), Owen (10), Ireton-Jones (11) and Mifflin-St Jeor (12). However, these equations have been challenged in the last decade because low accuracy (13) and, they may lead to over or underfeeding (14) mainly in the ICU. The purpose of this study was to compare the usual predictive equations to measurement of energy expenditure using indirect calorimetry in this specific population receiving home parenteral nutrition particularly exposed to complications related to over or under feeding, since receiving this regimen for months and years.
Material and methods
The study enrolled 76 patients aged 21 to 85 years (29 women and 47 men) hospitalized between January 2012 and May 2014. The study inclusion criterion was the necessity to implement home parenteral nutrition (HPN) due to: short bowel syndrome (SBS) ‘ 54%, intestinal fistulae ‘ 24%, cancer obstruction ‘ 16%, radiation- induced intestinal injury ‘ 6%. All patients were evaluated for risk related to their nutrition status (Nutritional Risk Score, NRS 2002). Prior to initiation of the home parenteral nutrition, the loss of ‘ 10% of baseline body weight over three months was diagnosed and the NRS-2002 score of ‘ 3 points was obtained. Patients qualified for the study had adequate circulatory and respiratory function and stable hemodynamic parameters (Table 1). Each patient was provided with specific information about the testing. All the patients consented to the procedure and IRB requirements were fulfilled.
1.1. Indirect calorimetry
Resting energy expenditure was assessed using an indirect calorimeter (CCM Express, MedGraphics). The first measurement was done after administration of a first nutrition bag, and the following measurement was done after the second TPN bags to ensure reliable results. The calorimeter was calibrated prior to each testing. The testing was done under the same conditions in all patients, i.e. at the same time (11:00 12:00 a.m.), in the same treatment room, in semi-supine position. Conditions in which the tests were performed met specific standards. Temperature in the study room was 24’C; patients did not receive enteral or parenteral nutrition for at least 3 hours before the measurement and did not participate in any physical activity for at least 30 minutes prior to testing. The duration of each test was 30 minutes and the study subject was instructed to remain motionless/at rest during this time.
1.2. Predictive equations
The equations evaluated in this study were including the 4 most commonly used and cited in the literature equations by: Harris and Benedict (HB), Owen, Ireton-Jones and Mifflin [9, 10, 11, 12 ] as well as the formulas proposed by the ESPEN, AuSPEN and BAPEN guidelines (20 to 35 kcal/kg/day).]. Table 2 presents these equations.
1.3. Statistical analysis
Analyses were done using SPSS V.21.0. All the results were expressed as mean ‘ standard deviation (SD). The agreement between REE and predictive energy expenditure values was analyzed using Bland Altman plots (15). The frequency (%) of energy expenditure estimates, using the different equations, to predict energy expenditure to within 80% and 110% of the REE was calculated. The number of estimates which were <80% or above 110% of MEE were also calculated. Cumulative energy balance that would have arisen had the patients been fed for 3 months according to prediction equation estimates was also evaluated. Assessment of predictions was done using a linear regression analysis and coefficient of determination R2.
Results
One hundred fifty two calorimetry measurements were performed among 76 patients, 2 times after the first and second TPN bags to ensure reliable results. Table 1 presents the characteristics of the study group. An average result of REE measurement by indirect calorimetry was 1181 ?? 322 kcal/day. The results in women were slightly lower than in men (1131 ?? 242 cal/day in the group of women, and 1212 ?? 361 kcal/day in the group of men) t(150) = 1,528 ; p=0,129. Variability in REE from one measurement to the other was 8 ?? 7%. Bland Altman analysis showed a mean bias of -192 ?? 300 kcal/day between REE and estimated energy expenditure using the HB equation (Fig 1) which means that the equation increase the score in average by 192 ?? 300 kcal/day. Limits of agreement between the 2 methods were -780 to +396 kcal/day (Table 3). Estimation energy expenditure using the Ireton-Jones equation gave a mean bias of -359 ?? 335 kcal/day (Fig 1). The limits of agreement between the 2 methods was -1015 to +297 kcal/day (Table 3). For Owen equation Bland Altman analysis showed a mean bias of -208 ?? 313 kcal/day (Fig 1) and the limits of agreement between the 2 methods was -822 to +406 kcal/day (Table 3). Using the Mifflin equation, estimation energy expenditure gave a mean bias of -172 ?? 312 kcal/day (Fig 1) and the limits of agreement between the 2 methods was -784 to +439 kcal/day (Table 3). Bland Altman analysis showed a mean bias of – 13 ?? 326 kcal/day for the 20 kcal/kg and the -909 ?? 436 for the 35 kcal/kg/day proposed by ESPEN guidelines (Fig 1). The wide limits of agreement in each case highlight the potential under and overfeeding of individual patients if such prediction equations were used. Since patients achieving intakes within 80 to 110% of target are described as “adequately fed”, and patients receiving <80% considered underfed and >110% overfed, we present in (table 4), the percentage of estimates calculated using the different equations, that fall into adequate, under and overfed categories. All 4 equations and 2 ESPEN recommendations were found to significantly predict the result of the calorimetric measurement, and the analyzed models were well-matched with the data; this is presented in Table 5. The largest part of variance of results among our patients was explained by the Ireton-Jones equation (R2 = 19%). The smallest part of variance was explained by the Owen equation (R2 = 11%) (Table 5). Table 5 presents also coefficients of an estimation error that indicate an estimated error which can be made by predicting the calorimetric result based on analyzed equations. An estimation error was 18-24%.
Discussion
To our knowledge, this is the first study comparing measured and calculated energy expenditure in HPN patients with concomitant malnutrition. Many authors have compared measured and predicted energy expenditure in a larger context. In hospitalized patients, Amirkalali et al. [16] compared the results obtained with the Harris-Benedict as well as the Mifflin equations with the results of indirect calorimetry. They found no significant difference between the calculated REE and MEE for both these equations, for the whole study group and in subgroups identified based on the reason for hospitalization. There were no significant differences for the Harris-Benedict equation in subgroups identified by sex, whereas the Mifflin equation was demonstrated to underestimate the obtained results in women and overestimate the results for men. Barak et al (17) divided the measured energy expenditure obtained from all the patients by their predicted energy expenditure calculated by the Harris Benedict equation and the ratio was considered as the stress factor for the hospitalized patients. HB formulas had to be increased by 25%. In ventilated patients, more studies are available. Kross et al. [18] demonstrated poor conformance between the Harris-Benedict equation and the results of indirect calorimetry in all studied BMI ranges, and in particular in subjects with overweight and obesity. The results obtained using the Owen and the Mifflin equations were underestimated to a higher degree than those calculated with the Harris-Benedict equation. A study published by Helems et al. evaluated REE in 42 liver transplant recipients during one year after the transplantation procedure. Having analyzed the IC data and the calculations based on the H-B equation, the author demonstrated a significant correlation between the obtained results [19]. The majority of published studies focused on evaluation of energy demand in obese subjects [20] or critically ill, mechanically ventilated patients [21, 22, 23].
When REE cannot be obtained by indirect calorimetry, we recommend the Ireton-Jones equation or the ESPEN 20 kcal/kg/day equation, based on the coefficient of determination (R2) as well as the estimation error levels. Our analyses indicate that the Ireton-Jones equation and the ESPEN 20 kcal/kg/day equation are the most reliable equation for patients with gastrointestinal insufficiency and malnutrition, who require parenteral nutrition (PN), It must be emphasized that all equations enable calculation of REE; however, the equation we recommend explains the highest rate of the results (coefficient of determination R2). In our studies, the coefficient of determination R2 for the Ireton-Jones equation was 41% for men and 23% for women. The obtained coefficients are not entirely satisfactory, and the prediction values are relatively low.
Our study has some limitations: The results are obtained from a single center, recruiting a relatively low number of patients. However, many diseases are represented and two measurements have been performed to each patient, a procedure rarely performed in other studies. We could conclude that the day to day variability is not influencing the measurement significantly.
2. Conclusions
Measurement of MEE using indirect calorimetry is strongly recommended in HPN patients since the prediction equations can lead to large negative or positive cumulative energy balance. Using the Bland Altman analysis, this study quantifies the level of inaccuracy associated with equations routinely used to predict energy expenditure or even recommended by international guidelines. If REE cannot be measured by indirect calorimetry (IC), the Ireton-Jones equation or the ESPEN equation of 20 kcal/kg/day appear, in our population, to be the most adequate method for REE calculation in malnourished patients in whom implementation of parenteral nutrition is planned. These findings have to be validated in other centers.
Author contribution
M?? was responsible for planning the article research design and for preparing the manuscript. PS reviewed the results and the manuscript. ??G, AG performed the statistical analysis. AB, KM collected and analyzed data. All authors read and approved the final manuscript.
Conflict of interest statement
Each author declared no conflict of financial or personal interests in this study.

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