Validation of a method for estimating pulmonary dead space in ventilated beagles to correct exhaled propofol concentration in mixed air.

Abstract

Background: Mixed exhaled air has been widely used to determine exhaled propofol concentrations with online analyzers, but changes in dead space proportions may lead to inaccurate assessments of critical drug concentration data. This study proposes a method to correct propofol concentration in mixed air by estimating pulmonary dead space through reconstructing volumetric capnography (Vcap) from time-CO₂ and time-volume curves, validated with vacuum ultraviolet time-of-flight mass spectrometry (VUV-TOF MS).

Methods: Existing monitoring parameters, including time-volume and time-CO₂ curves, were used to determine Vcap. The ratio of physiological dead space to tidal volume (V_D/V_T) was calculated using Bohr's formula. Additionally, an animal experiment on beagles was conducted with continuous propofol administration until a pseudo-steady state in exhaled propofol concentration was achieved. The propofol concentration in mixed air (CONC_mix), and in alveolar air combined with N₂ (CONC_AN) were measured using VUV-TOF MS to calculate V_D/V_T. The agreements between V_D/V_T values from the two methods, along with the predicted CONC_AN values based on Vcap and the actual measured CONC_AN values were evaluated using the intraclass correlation coefficient (ICC) and Pearson correlation analysis.

Results: After 30 min of continuous propofol administration, a stable respiratory cycle was selected for analysis in each beagle. The calculated V_D/V_T-Bohr values were 0.535 for beagle A, 0.544 for beagle B, and 0.552 for beagle C. Additionally, based on CONC_mix and CONC_AN, the calculated V_D/V_{T-VUV-TOF MS} values were 0.494, 0.504, and 0.513, respectively. Strong agreement between the two methods was demonstrated by an ICC of 0.994 (P = 0.003) and Pearson's r of 0.995 (P = 0.045). Additionally, the predicted CONC_AN values from mixed exhaled air (5.11 parts per billion by volume (ppbv) for beagle A, 5.93 ppbv for beagle B, and 2.56 ppbv for beagle C) showed strong agreement with the actual CONC_AN values, with an ICC of 0.996 (P = 0.002) and Pearson's r of 0.994 (P = 0.046).

Conclusion: The physiological dead space to tidal volume ratio from mixed air in beagles can be accurately measured using the existing time-volume and time-CO₂ curves from the anesthesia machine, enabling corrections of exhaled propofol concentrations in mixed air samples.