Energy expenditure and substrate utilization during critical illness

Background: Critical illness leads to major alterations in metabolism. The net result is a state where catabolism predominates over anabolism. The associated loss of lean body mass is significant and potentially harmful. It is commonly held that providing calories and protein from nutrition may attenuate this response. Despite significant research efforts, an optimal dose for these therapies remains to be defined. The metabolic rate of ICU patients is readily measured by indirect calorimetry. Questions regarding the accuracy of modern instruments in the setting of mechanical ventilation have been an impediment to wider application of this technique. The physiological effects of common nutritional interventions on protein balance are difficult to assess in clinical practice but can be quantified using stable isotope tracers.

Aims: The studies of this thesis had two main aims: to validate techniques for gas exchange measurements in ICU, and to describe the effects of energy and/or amino acid supplementation on protein kinetics. In studies I and II we evaluated the measurement properties of three new instruments for indirect calorimetry in mechanically ventilated ICU patients against a clinical gold standard (Deltatrac). Study III investigated the effects of a supplemental amino acid infusion on whole-body protein balance in critically ill patients. In study IV, we quantified whole-body protein kinetics after 24 hours of full-dose or half-dose enteral nutrition in a randomized cross-over study design.

Results: In study I, we performed 48 measurements with the evaluated instruments and reference method in sequence. Mean resting energy expenditure (REE) was similar between Quark RMR and Deltatrac (p = 0.17). Mean REE from CCM Express was 64% higher than Deltatrac (p <0.001). In study II we conducted 48 simultaneous measurements with the evaluated instruments and Deltatrac. Compared to Deltatrac, both Quark RMR and E-sCOVX overestimated REE with similar bias and 95% limits of agreement. In study III, a 24-hour intravenous amino acid infusion resulted in a positive protein balance during the study period (p = 0.0016) without increasing amino acid oxidation (p = 0.147). In study IV, whole-body protein kinetics could be determined in six patients during half-dose and full-dose enteral nutrition. An improvement in protein balance was observed during full-dose nutrition (p = 0.044).

Conclusions: Measured energy expenditure is variable between instruments for indirect calorimetry. Apart from one device, agreement compared to the reference method was better than what is commonly accepted for other monitoring technologies in critical care. The studies of protein kinetics indicate that an increase in energy or amino acid delivery improves whole-body protein balance in critically ill patients. Indirect calorimetry and tracer techniques are promising methods to further our understanding of alterations in energy metabolism and substrate utilization during critical illness. In turn, this knowledge may assist in the development of clinical trials with patient-centered outcomes.

List of scientific papers

I. Indirect calorimetry in mechanically ventilated patients: A systematic comparison of three instruments. Sundström M, Tjäder I, Rooyackers O, Wernerman J. Clin Nutr. 2013 Feb;32(1):118-21.
https://doi.org/10.1016/j.clnu.2012.06.004

II. Measuring energy expenditure in the intensive care unit: a comparison of indirect calorimetry by E-sCOVX and Quark RMR with Deltatrac II in mechanically ventilated critically ill patients. Sundström Rehal M, Fiskaare E, Tjäder I, Norberg Å, Rooyackers O, Wernerman J. Crit Care. 2016 Mar 5;20:54.
https://doi.org/10.1186/s13054-016-1232-6

III. A supplemental intravenous amino acid infusion sustains a positive protein balance for 24 hours in critically ill patients. Sundström Rehal M, Liebau F, Tjäder I, Norberg Å, Rooyackers O, Wernerman J. Crit Care. 2017 Dec 6;21(1):298.
https://doi.org/10.1186/s13054-017-1892-x

IV. Whole-body protein kinetics in critically ill patients during 50 or 100% energy provision by enteral nutrition: A randomized cross-over study. Sundström Rehal M, Liebau F, Wernerman J, Rooyackers O. [Submitted]