Cardiovascular parameters continue to change after achieving constant effect site drug concentration

Abstract

There is a good correlation between the calculated effect site concentration and the depth of anaesthesia. Propofol is known to depress the cardiovascular system but the relationship between the effect site concentration and cardiovascular depression has not been extensively studied. A previous study by Kazama et al. showed that the maximal cardiovascular depression (using systolic blood pressure only) would happen some 8 min after peak plasma propofol concentrations [1]. We wished to investigate this further while using effect site concentration target-controlled infusions (TCI) of total intravenous anaesthesia (TIVA). Local Research Ethics Committee approval was given and informed consent obtained from 20 patients of ASA physical status 1–2 due to undergo elective day surgery. They were then anaesthetised using a standard effect site concentration TIVA technique. From the time of attaining a steady state effect site concentration of both propofol and remifentanil ([ES]ss) we measured Bispectral Index, heart rate, blood pressure and cardiac index every minute for 25 min. Any alterations were then mathematically modelled in a nonlinear regression model to calculate when they reached a steady plateau with 95% certainty. These are shown in Table 1. We have shown that the time to maximal cardiovascular depression occurs well after that previously claimed [1]. The depression of cardiovascular parameters is most profound in the vasodilatation that is well known with propofol, reflected in the drop in mean arterial pressure. The reduction in heart rate is also significant but reflex mechanisms of increasing the stroke volume ensures that the measured cardiac index changes less. These results show that after achieving steady state concentrations of anaesthetic agents the cardiovascular system depresses further with a maximal time of depression ∼78 min after achieving calculated steady state anaesthesia. Papers using patients at ‘steady state’ anaesthesia must either have a comparable control arm to the experiment or wait for 78 min until the cardiovascular systems achieve a steady plateau.