A computer controlled infusion device for propofol was used to induce and maintain general anaesthesia in 20 children undergoing minor surgical procedures. The device was programmed with an adult pharmacokinetic model for propofol. During and after anaesthesia, blood samples were taken for measurement of propofol concentrations and it was found that the values obtained were systematically overpredicted by the delivery system algorithm. New pharmacokinetic microconstants were derived from our data which reflected more accurately the elimination and distribution of propofol in a prospective study involving another 10 children.
We studied four electrophysiological variables (bispectral index (BIS), 95% spectral edge frequency (SEF), median frequency (MF) and auditory evoked potential index (AEP index) in 10 patients during emergence from anaesthesia. We compared correlation of the signals with gradually decreasing calculated blood propofol concentrations, and evaluated the signal differences between preinduction and emergence from anaesthesia. Values of BIS, MF and SEF correlated with calculated blood concentrations of propofol during emergence from anaesthesia. The correlation was best with BIS, but was poor with MF and SEF at low calculated blood propofol concentrations. Although AEP index values did not correlate with calculated blood concentrations of propofol during emergence from anaesthesia, values after eye opening and before anaesthesia were well distinguished from those during emergence from anaesthesia. BIS correlated best with calculated blood concentrations of propofol. AEP index appeared to distinguish the awake from asleep state.
During propofol TCI in healthy patients, the decrease in pupil response to a painful stimulus is a better measurement of the progressive increase of remifentanil Ce(T) up to 5 ng ml(-1) than haemodynamic or BIS measurements.
Key wordsAnaesthetics, intravenous; propofol. Equipment; computers, infusion pumps.There has been interest for many years in the maintenance of anaesthesia with intravenous drugs as an alternative to inhalational agents.' The withdrawal of propanidid and Althesin, and the problems related to suppression of adrenocortical function with etomidate, have led to the emergence of propofol as the most suitable intravenous anaesthetic for this purpose. Propofol offers many advantages as a total intravenous anaesthetic in terms of its pharmacokinetic profile,2 but anaesthetists are not familiar generally with the use of intravenous agents to maintain anaesthesia compared with standard volatile anaesthetics delivered via calibrated vaporizers.Various suggestions have been proposed for suitable infusion rates of propofol to maintain satisfactory anaesthesia.'.4 Roberts et al. ' have proposed a manual infusion scheme designed to achieve a constant blood level throughout the duration of surgery and the success of this regimen has been confirmed during computer-controlled infusion of propofol,' intended also to maintain a constant blood concentration during anaesthesia. However, such a scheme has the principal disadvantage of inability to vary the blood propofol concentration in response to changing surgical and anaesthetic requirements. Volatile agents may then have to be introduced to maintain adequate anaesthesia." Consequently, we believe that there is a need for a system which enables the anaesthetist to alter the depth of anaesthesia in as simple a manner as that used for volatile agents. We have constructed a computer-controlled device for the infusion of propofol which fulfils this requirement. The performance of the system has been evaluated by comparing the predicted blood concentrations of propofol selected by the anaesthetist to produce a satisfactory level of anaesthesia with the values measured from blood samples.
Methods
Coniputer systemThe pharmacokinetic variables which influence the distribution and elimination of propofol? have been incorporated into a computerised delivery system which is designed to allow the anaesthetist at any time to achieve and maintain the desired blood concentration of propofol.The predicted blood concentration is achieved by a preselected rapid zero-order infusion and thereafter is controlled automatically to maintain the concentration at the desired level. Our system incorporates a three-compartment mathematical model of the pharmacokinetics of M.
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