Methods to validate the accuracy of an indirect calorimeter in the in-vitro setting

The international ICALIC initiative aims at developing a new indirect calorimeter according to the needs of the clinicians and researchers in the field of clinical nutrition and metabolism. The project initially focuses on validating the calorimeter for use in mechanically ventilated acutely ill adult patient. However, standard methods to validate the accuracy of calorimeters have not yet been established. This paper describes the procedures for the in-vitro tests to validate the accuracy of the new indirect calorimeter, and defines the ranges for the parameters to be evaluated in each test to optimize the validation for clinical and research calorimetry measurements.

Two in-vitro tests have been defined to validate the accuracy of the gas analyzers and the overall function of the new calorimeter. 1) Gas composition analysis allows validating the accuracy of O₂ and CO₂ analyzers. Reference gas of known O₂ (or CO₂) concentration is diluted by pure nitrogen gas to achieve predefined O₂ (or CO₂) concentration, to be measured by the indirect calorimeter. O₂ and CO₂ concentrations to be tested were determined according to their expected ranges of concentrations during calorimetry measurements. 2) Gas exchange simulator analysis validates O₂ consumption (VO₂) and CO₂ production (VCO₂) measurements. CO₂ gas injection into artificial breath gas provided by the mechanical ventilator simulates VCO₂. Resulting dilution of O₂ concentration in the expiratory air is analyzed by the calorimeter as VO₂. CO₂ gas of identical concentration to the fraction of inspired O₂ (FiO₂) is used to simulate identical VO₂ and VCO₂. Indirect calorimetry results from publications were analyzed to determine the VO₂ and VCO₂ values to be tested for the validation.

O₂ concentration in respiratory air is highest at inspiration, and can decrease to 15% during expiration. CO₂ concentration can be as high as 5% in expired air. To validate analyzers for measurements of FiO₂ up to 70%, ranges of O₂ and CO₂ concentrations to be tested were defined as 15-70% and 0.5-5.0%, respectively. The mean VO₂ in 426 adult mechanically ventilated patients was 270 ml/min, with 2 standard deviation (SD) ranges of 150-391 ml/min. Thus, VO₂ and VCO₂ to be simulated for the validation were defined as 150, 250, and 400 ml/min.

The procedures for the in-vitro tests of the new indirect calorimeter and the ranges for the parameters to be evaluated in each test have been defined to optimize the validation of accuracy for clinical and research indirect calorimetry measurements. The combined methods will be used to validate the accuracy of the new indirect calorimeter developed by the ICALIC initiative, and should become the standard method to validate the accuracy of any future indirect calorimeters.