EDITORIAL URRENT C OPINION

Too little or too much are inadequate Claude Pichard, Didier Attaix, and Vickie E. Baracos

Indirect calorimetry is the reference method to measure energy expenditure of in-patients and outpatients. Briefly, the continuous collection of inspiratory and expiratory gases allows the determination of O2 consumption and CO2 production. Then, the energy expenditure is calculated by using the energy value equivalent to the measured gas volumes [1]. The need for accurate determination of energy expenditure is increasing because of the rising prevalence of patients with clinical conditions associated with unpredictable variation of the ratio of body weight/energy expenditure. For example, very old individuals with reduced lean body mass and increased fat mass, have a reduced energy expenditure. Similarly, patients with cachexia related to cancer, anorexia nervosa, chronic obstructive pulmonary disease, chronic infectious, prolonged stay in the ICU, or those with reduced muscle activity, such as in case of extensive muscle paralysis or degenerative conditions (tetraplegia, paraplegia, and muscle sclerosis) or chronic neurological diseases, have a significant reduction of their energy expenditure, but of variable magnitude. On the contrary, young patients with severe trauma or burn, acute or chronic infection, or those with severe obesity have increased energy expenditure. A number of studies have shown that predictive formulae developed to predict energy expenditure of such patients are clinically not relevant. The principle flaw of these equations is that they are not able to correctly estimate the mass of metabolically active (i.e., lean) tissue. A related issue is that there is also a crucial lack of accurate and precise measurements of body composition that can be used at the bedside, so that the equations cannot be corrected. We, therefore, rely on predictive formulae for energy expenditure that are inaccurate in 30–40% of ICU patients [2]. When comparing these equations with measured values by indirect calorimetry, the difference varies from 40% below or above the physiological needs and results in underfeeding or overfeeding, both conditions that are associated with excess morbidity. Indeed, clinicians need to measure their patient’s energy expenditure to optimize the prescription of nutritional support and to thereby gain clinical benefit. This statement is supported by

recent important studies on the impact of nutrition intervention, which have generated different results [3–6]. Diverging conclusions are mostly related to the overinterpretation of a mixture of independent factors, namely the timing (early vs. late) and the route (enteral vs. parenteral) of nutrition, the patient’s diseases (surgical vs. medical), and the adequacy (under/over) of energy provision. Among the explanations for these conflicting results, the inadequate provision of energy is the most prevalent [7,8]. All recent clinical trials pointed to the need for accurate measurement of energy expenditure. In theory, indirect calorimetry measurement allows precise determination of the patient’s energy expenditure in case of spontaneous breathing, as well as during mechanical ventilation. Most of the clinical studies using indirect calorimetry used equipment developed 30 years ago (Deltatrak, Datex, Finland). This equipment has been discontinued, and a few manufacturers have developed their own indirect calorimetry devices. Recent prospective studies have shown that these new devices have insufficient accuracy and can, therefore, not be recommended for clinical practice without some limitations [9–11]. Indeed, statistical analysis revealed that they were as unreliable as predictive formulae based on age, sex, body weight, and height (see Harris–Benedict formula). Insufficient testing in clinical settings and lack of collaboration with clinicians mostly explain this poor outcome. This observation has stimulated an international consortium of clinicians to develop a new indirect calorimetry device. In reaction, two large academic societies (The European Society for Clinical Nutrition and Metabolism and The European Society of Intensive Care Medicine) are supporting the project, which includes the definition of the technical characteristics, the proof-ofconcept, and clinical feasibility tests. The technical Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland Correspondance to Professor Claude Pichard, MD, PhD, Head, Clinical Nutrition, Geneva University Hospital, 1211 Geneva, Switzerland. Tel: +41 22 37 29 349; fax: +41 22 372 9363; e-mail: claude.pichard @unige.ch Curr Opin Clin Nutr Metab Care 2014, 17:211–212 DOI:10.1097/MCO.0000000000000055

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Translational research in wasting diseases

characteristics have been defined by a bottom-up strategy, and an industrial developer did accept the challenge to create a completely new indirect calorimetry device. A prototype is about to be released, which features two types of characteristics: (1) Critical: easy-to-use, with sufficient accuracy levels and precision for clinical and research use, easy disinfection procedure, and low cost ($10 000). (2) Important: no warming up delay, flexible site for sampling, fast sampling rate, compatibility with most mechanical ventilators, working with an oxygen enrichment fraction (FiO2) up to 70%, reduced-weight and reduced-size instrument, no calibration gas required, and low sensitivity to physical displacements. A prospective multicenter study of the prototype will be launched in six countries in 2014. It is hoped that the new indirect calorimetry device will meet clinical needs and allows for quick, reliable, and affordable determination of patient’s energy requirements. Such an evolution will significantly contribute to the routine optimization of nutritional support. It should also allow for the systematic use of calorimetry in clinical trials, which should promote the quality of the results and facilitate their interpretation. Acknowledgements None.

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Conflicts of interest C.P. has received two official grants to develop a new indirect calorimetry device from the European Critical Care Research Network, European Society of Intensive Care Medecine (ESICM), and from the European Society Of Clinical Nutrition and Metabolism (ESPEN).

REFERENCES 1. Guttormsen AB, Pichard C. Determining energy requirements in the intensive care unit. Curr Opin Clin Nutr Metab Care 2014; 17:171–176. 2. McClave SA, Martindale RG, Kiraly L. The use of indirect calorimetry in the intensive care unit. Curr Opin Clin Nutr Metab Care 2013; 16:202– 208. 3. Heidegger CP, Berger MM, Graf S, et al. Optimization of energy provision with supplemental parenteral nutrition (SPN) improves the clinical outcome of critically ill patients: a randomized controlled trial. Lancet 2013; 381:385– 393. 4. Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011; 365:506–517. 5. Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013; 368:1489–1497. 6. Doig G, Simpson F, Sweetman EA, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. JAMA 2013; 309:2130– 2138. 7. McClave S, Heyland D, Martindale R. Adding supplemental parenteral nutrition to hypocaloric enteral nutrition: lessons learned from the Casaer Van den Berghe study. JPEN J Parenter Enteral Nutr 2012; 36:15–17. 8. Singer P, Pichard C. Reconciling divergent results of the latest parenteral nutrition studies in the ICU. Curr Opin Clin Nutr Metab Care 2013; 16:187– 193. 9. Sundstrom M, Tjader I, Rooyackers O, Wernerman J. Indirect calorimetry in mechanically ventilated patients. A systematic comparison of three instruments. Clin Nutr 2013; 32:118–121. 10. Graf S, Karsegard V L, Viatte V, et al. Evaluation of three indirect calorimetry devices in mechanically ventilated patients: which device compares best with the Deltatrac II? A prospective observational study. Clin Nutr 2014. [Epub ahead of print]. doi: 10.1016/j.clnu.2014.01.008. 11. Graf S, Karsegard V L, Viatte V, et al. Comparison of three indirect calorimetry devices and three methods of gas collection: A prospective observational study. Clin Nutr 2013; 32:1067–1072.

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Too little or too much are inadequate.

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