Comparison of different methods of chemical loop gain measurement during tidal ventilation in awake healthy subjects.

The loop gain (LG) is defined as the ratio of a ventilatory response over the perturbation in ventilation, and it is used to analyze ventilatory control stability. The LG can be derived from minute ventilation (VE), end-tidal PCO2 (PETCO2) and PETO2 values. Several methods of LG assessment have been developed, which have never been compared. We evaluated the computability, the short term repeatability and the agreement of six published (or slightly modified) models for LG determination. These models included three unconstrained autoregressive models: univariate (VE), bivariate (VE, PETCO2) and trivariate (VE, PETCO2 and PETO2) and three analytical transfer function constrained models based on VE, VE and CO2-sensitivity, and VE, central and peripheral CO2-sensitivities, respectively. The models were tested using tidal breathing data in 37 awake healthy subjects (median age, 35 years, 23 women). Modelling failed in 11, 0, and 0 subjects for the three unconstrained models respectively, and 4, 1, and 9 subjects for the three constrained models, respectively. Bland and Altman analyses of the LG values in the medium frequencies range of two separate recordings demonstrated good repeatability for four models, excluding univariate and trivariate unconstrained models. The four repeatable models gave LG values that were in agreement (medium frequencies LG, median 0.100 to 0.210), although the constrained model based on VE systematically overestimated LG values. The variances explained by these models were around 20%. In conclusion, model-based analyses of tidal breathing were performed using different approaches that give comparable results of chemical LG and explained variance.