Anesthesiology. 2025 Aug 7. doi: 10.1097/ALN.0000000000005710. Online ahead of print.
ABSTRACT
BACKGROUND: Opioids are associated with potentially severe ventilatory depression. However, in the perioperative setting, when opioids are combined with anesthetics, we remain uninformed on their “isolated” effects on ventilatory control.
METHODS: In twelve healthy volunteers of either sex, we tested the effect of 5 clinical doses of fentanyl (initial dose 100 µg, followed by 75 µg at t = 30 and 60 min and 50 µg at t = 90 and 120 min). We measured minute ventilation, end-tidal CO2 concentrations and arterial fentanyl concentrations during the sham procedure and for another hour. Pharmacokinetic-pharmacodynamic modeling was conducted using three distinct models: a model describing just ventilation, one describing just end-tidal CO2 concentrations and a physiological model in which ventilation and end-tidal CO2 concentrations were modelled simultaneously and closed loop conditions and CO2 kinetics were considered. We hypothesized that the physiological model yields the most reliable estimation of fentanyl’s ventilatory potency. Parameter values are median ± standard error of the estimate.
RESULTS: The value of the fentanyl potency parameter, C50 or the steady-state fentanyl concentration causing 50% depression of ventilation, derived from the physiological model, was less than one-third of those derived from the separate models for VE: 2.3 ± 0.5 versus 7.5 ± 1.3 ng/mL (typical value ± standard error of the estimate). Few other differences in mutual parameter values between models were observed. Parameters exclusive to the physiological model were the gain and time constant of the ventilatory controller, with values 5.3 ± 1.4 L.min-1.kPa-1 and 2.4 ± 1.4 min, respectively, and tissue volume (53 ± 10 L).
CONCLUSIONS: In this exploratory and hypothesis generating study, the pharmacodynamic model that incorporates CO2 kinetics and a ventilatory controller produced a fentanyl potency estimate that was lower than that estimated from simpler models lacking these components, a value that we consider pharmacologically realistic and clinically relevant.
PMID:40773676 | DOI:10.1097/ALN.0000000000005710
Recent Comments