Indirect calorimetry is the gold standard to assess REE in ICU patients: some limitations to consider

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. In their metanalysis, Duan et al. address the role of indirect calorimetry (IC) in nutritional therapy in critically ill patients [1].Their findings support using IC rather than predictive equations as the gold standard to assess resting energy expenditure (REE) [1]. Previous studies have demonstrated the low accuracy of various REE predictive equations based on weight, height, age, gender, etc. [1]. Despite adjustments according to patient population and other modifying factors, REE discrepancies remain, (with variations up to 60%) [1]. IC allows for the measurement of VO2 and VCO2 through the ventilator and is the gold standard method for measuring REE in ICU, when ideal test conditions are implemented [1]. Both the European (ESPEN) and American (ASPEN) clinical practice guidelines recommend the use of IC to measure REE [2]. While supporting the use of IC in some settings, we wish to point out a number of limitations, particularly when patients are undergoing continuous renal replacement therapy (CRRT) [3] and extracorporeal membrane oxygenation (ECMO) [4, 5]. Estimating REE using IC in CRRT patients is less reliable for several reasons [3]. First, CO2 from bicarbonate-based dialysate can pass the filter and circulate in the form of dissolved CO2, bicarbonate, or carbamino compounds in red blood cells or plasma [3]. Though a quantity of CO2 may be removed in the effluent [3], a recent study showed that CO2 removal by CRRT led to a minimal change of 3% of measured EE [3] Second, patients may experience heat loss up to 1000 kcal during CRRT, resulting in increased metabolism and REE [3]. Third, dialysate compositions and citrate also contribute to caloric uptake [3]. For all these reasons, IC remains less reliable during CRRT and more research should shed light [3]. This is also true for IC performed in patients on ECMO, unless a mathematical correction is applied [3]. It is important that clinicians are aware not only of the indications for IC, but also its limitations. [3]. Other technical limitations of IC in ICU are discussed in a comprehensive review to which readers should refer [5].

In their metanalysis, Duan et al. address the role of indirect calorimetry (IC) in nutritional therapy in critically ill patients [1].Their findings support using IC rather than predictive equations as the gold standard to assess resting energy expenditure (REE) [1]. Previous studies have demonstrated the low accuracy of various REE predictive equations based on weight, height, age, gender, etc. [1]. Despite adjustments according to patient population and other modifying factors, REE discrepancies remain, (with variations up to 60%) [1]. IC allows for the measurement of VO2 and VCO2 through the ventilator and is the gold standard method for measuring REE in ICU, when ideal test conditions are implemented [1]. Both the European (ESPEN) and American (ASPEN) clinical practice guidelines recommend the use of IC to measure REE [2]. While supporting the use of IC in some settings, we wish to point out a number of limitations, particularly when patients are undergoing continuous renal replacement therapy (CRRT) [3] and extracorporeal membrane oxygenation (ECMO) [4,5]. Estimating REE using IC in CRRT patients is less reliable for several reasons [3]. First, CO2 from bicarbonate-based dialysate can pass the filter and circulate in the form of dissolved CO2, bicarbonate, or carbamino compounds in red blood cells or plasma [3]. Though a quantity of CO2 may be removed in the effluent [3], a recent study showed that CO2 removal by CRRT led to a minimal change of 3% of measured EE [3] Second, patients may experience heat loss up to 1000 kcal during CRRT, resulting in increased metabolism and REE [3]. Third, dialysate compositions and citrate also contribute to caloric uptake [3]. For all these reasons, IC remains less reliable during CRRT and more research should shed light [3]. This is also true for IC performed in patients on ECMO, unless a mathematical correction is applied [3]. It is important that clinicians are aware not only of the indications for IC, but also its limitations. [3]. Other technical limitations of IC in ICU are discussed in a comprehensive review to which readers should refer [5].
Response to the letter to the editor: "Using indirect calorimetry in place of fixed energy prescription was feasible and energy targets were more closely met: do not forget an important limitation"

Hui-Bin Huang, Jing-Yi Duan, Yuan Xu and Hua Zhou
We thank Professor Honore et al. for their interest in our meta-analysis [1]. Our study identified 8 RCTs and demonstrated that compared with predictive equations, indirect calorimetry (IC) guided energy delivery can significantly reduce short-term mortality in critically ill
*Correspondence: Patrick.Honore@CHU-Brugmann.be 1 ICU Dept, Centre Hospitalier Universitaire Brugmann-Brugmann University Hospital, Place Van Gehuchtenplein, 4, 1020 Brussels, Belgium Full list of author information is available at the end of the article patients without affecting other important clinical outcomes such as hospital stay and mechanical ventilation.
We fully agree with what Professor Honore and colleagues pointed out that clinicians need to understand not only indications of IC but its limitations [6]. Especially, Professor Honore highlighted that the use of IC might be unreliable in patients undergoing continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). Indeed, although all included RCTs in our meta-analysis provided detailed IC indications, only two trials had excluded patients receiving CRRT, and no trials reported having excluded patients with ECMO [1].
Cardiopulmonary bypass can remove part of VCO2, which is considered the most important technical factor affecting the reliability of IC measurement [6]. However, this does not mean that patients who receive CRRT or ECMO are bystanders of the IC technique. In a monocentric, controlled, prospective, observational pilot study, Wollersheim, and colleagues proposed measuring the reliability of energy expenditure (EE) in extracorporeal lung support patients by calculating the O2 uptake and the CO2 elimination by the ECLS membrane, then using sum O2 uptake and CO2 elimination in the equation of Weir to calculate EE [7].
Although CRRT may be more complicated due to factors such as replacement fluid, Jonckheer et al. proposed a simple blood gas analysis based on the circuit to quantify CO2 that was removal during continuous venovenous hemofiltration. In their study, the CO2 content in ultrafiltration is available by blood gas analysis, and the CO2 content is converted from mmoL to mL with the help of the ideal gas law (pV = nRT). The authors performed IC in 4 different states (baseline, high dose, baseline with NaCl predilution and without CVVH) and found that CO2 removal by CVVH led to a change in REE of only 3%, which makes a correction factor unnecessary in this setting [8]. Although the authors believed that citrate might be the only factor that significantly changes metabolism out of all the potential metabolic influences during CVVH, they also admitted that this required further research [8].