A preclinical study on online monitoring of exhaled ciprofol concentration by the ultraviolet time-of-flight spectrometer and prediction of anesthesia depth in beagles.

BACKGROUND: Exhaled air has been demonstrated as a reliable medium for monitoring propofol concentration. However, online monitoring of exhaled ciprofol have not been reported. METHODS: Thirty-six beagles undergoing mechanical ventilation were divided into 6 groups, including bolus injection of low (Group BL, n = 6), medium (Group BM, n = 6), and high dose of ciprofol (Group BH, n = 6) groups; as well as 1 h continuous infusion of low (Group IL, n = 6), medium (Group IM, n = 6), and high dose of ciprofol (Group IH, n = 6) groups. The ciprofol concentration in exhaled air (CE) was determined by the ultraviolet time-of-flight mass spectrometer (UV-TOFMS). The correlations of CE and plasma concentration (Cp), CE and the bispectral index (BIS) were explored. Additionally, the pharmacokinetics (PK) models of CE and Cp, the pharmacodynamics (PD) models of CE and BIS were also established. RESULTS: Online monitoring of exhaled ciprofol can be achieved with the UV-TOFMS instrument. The CE of ciprofol in beagles was found at parts per billion by volume (ppbv) level. The linear correlation of CE and Cp was weak in bolus injection groups (R2 = 0.01) nonetheless moderate in continuous infusion groups (R2 = 0.53). The i.v. bolus PK model of CE and Cp can be fitted with the non-compartment models. Additionally, the the PD models of CE and BIS can be well fitted with the inhibitory sigmoid Emax model with the estimate values of IC50 = 0.05 ± 0.01 ppbv, γ = 4.74 ± 1.51, E0 = 81.40 ± 3.75, Imax = 16.35 ± 4.27 in bolus injection groups; and IC50 = 0.05 ± 0.01 ppbv, γ = 6.92 ± 1.30, E0 = 83.08 ± 1.62, Imax = 12.58 ± 1.65 in continuous infusion groups. CONCLUSIONS: Online monitoring of exhaled ciprofol concentration in beagles can be achieved with the UV-TOFMS instrument. Good correlations can be observed between exhaled ciprofol concentration and its cerebral effects reflected by the BIS value, demonstrating the potential of exhaled ciprofol monitoring for titrating depth of anesthesia in future clinical setting.