Modelling the dynamic ventilatory response to hypoxia in humans

Abstract

A two-component dynamic model was used to describe the ventilatory response to sustained hypoxia in humans. One component (Xs) represents the stimulating effects of hypoxia and the other component (Xd), the hypoxic ventilatory decline. The total ventilatory response to hypoxia is represented by the sum of the two components. A nonlinearity is included to account for the nonlinear steady-state ventilatory response to hypoxia. A sensitivity analysis of the model indicates that, with a step change in F(ETO2) as the input, all the parameters can be estimated from the data except for the nonlinearity. The relative sensitivity of the parameters from the model analysis was confirmed in an experimental study. However, comparing steps into hypoxia versus steps out of hypoxia we found a decrease in the gains of both components. The most likely explanation for the decrease in the gains is that the combination of Xs and Xd is not entirely additive. Other models may be required to completely describe the ventilatory response to inputs more complex than steps.

Modeling the Non–Steady State Respiratory Effects of Remifentanil in Awake and Propofol-sedated Healthy Volunteers

“…A sensitivity analysis of a proposed model will indicate whether the parameter values of the model can be estimated with finite precision from the measured data. 20 The parameters may not be estimable for various reasons: because of the model structure, dependence on other parameters, or the specific input function chosen. We performed a sensitivity analysis of simulated data in which C REM increases to 5 ng/ml in five steps using three distinct input functions: (1) step size ϭ 1 ng/l, duration of step ϭ 1 min; (2) step size ϭ 1 ng/ml, duration of step ϭ 5 min; and (3) step size ϭ 1 ng/ml, duration of step ϭ 0.1 min.…”

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

“…They are considered a critical defense mechanism to preserve oxygen delivery to the brain. The response to both isocapnic and poikilocapnic hypoxia has been well characterized in humans and animals (42,149,206,551,740). Duffin et al (150) first showed a selective depression of the peripheral chemoresponse by halothane compared to barbiturates in man.…”

“…In the awake human, even moderate hypoxia causes swift hyperventilation (206,740). The response to acute hypoxia originates from the peripheral chemoreceptors in the CB.…”