In this study, differences, effective doses, and concentrations of propofol and thiopental in hypnotic, analgesic, and EEG end-point were evaluated. Nine New Zealand White rabbits, and 143 patients scheduled for elective surgical procedures were studied. Infusions of propofol and thiopental were used in all studies (I-V); bolus doses were used as an induction of anaesthesia in study II before the infusion of the anaesthetic agent started. Furthermore, in study III there was two bolus groups (loss of reflexes) as controls. In addition to propofol and thiopental, ketamine was used in study I.

A comparison of ketamine, propofol, and thiopental in rabbits revealed propofol to be the best choice during non-noxious diagnostic procedures because recovery was rapid and breathing patterns were well preserved during infusion. Recovery was prolonged after thiopental and ketamine. Effective doses and concentrations for hypnotic and analgesic end-points were defined. The main metabolites of ketamine in rabbits were norketamine and dihydronorketamine.

Alfentanil 17.5 microg/kg given 2 min before tracheal intubation with propofol 2.0 mg/kg or thiopental 5 mg/kg, followed by infusion attenuated arterial pressure response but not heart rate response. Neither infusion of propofol (12 mg/kg/h) nor infusion of thiopental (18 mg/kg/h) could attenuate the cardiovascular or catecholamine response to the insertion of the operating laryngoscope 10 min after alfentanil bolus. The response of SAP and ADR was more pronounced with thiopental. According to the present study, propofol better attenuates the catecholamine response to tracheal intubation than thiopental, especially the NOR response. This partially explains the differences in cardiovascular responses to tracheal intubation between propofol and thiopental. In fact, CA response to tracheal intubation was almost totally blocked during burst suppression pattern (BSP) of EEG induced by propofol. It is obvious that neither propofol nor thiopental alone can totally block the cardiovascular response to tracheal intubation. This shows that mechanical stimuli from the larynx and the base of the tongue are important in mediating the cardiovascular responses to tracheal intubation.

Our hypothesis that more precise information might be obtained on the reaction to tracheal intubation when unconsciousness is controlled by aid of the BSP instead of clinical signs was not supported. Levene s test showed insignificant differences of variance between BSP level anaesthesia compared with loss of reflexes level anaesthesia. Cardiovascular reflexes were still highly variable at BSP level except for the loss of catecholamine response with propofol. However, we did find that at BSP level, thiopental attenuated the hemodynamic response to intubation nearly as well as propofol.

The effective doses of thiopental at hypnotic and EEG end-points were determined. Remifentanil infusion started before the infusion of propofol significantly reduced times and doses of propofol at the attainment of hypnotic, analgesic and BSP end-points. Remifentanil also affects the BIS value at BSP onset level. However, when remifentanil was present, plasma concentrations of propofol were not reduced at BSP end-point as they were in hypnotic and analgesic end-points. These results suggest that remifentanil is kinetically useful for loss of consciousness because it accelerates the hypnotic onset of propofol.

The arterial concentrations of thiopental and propofol at the onset of BSP were determined. Propofol and thiopental have certain similarities in burst suppression pattern of EEG, but differences exist especially in the terminal parts of the bursts. During BSP induced by propofol 13-15 Hz spindle oscillations are seen both during bursts and suppressions. These oscillations are also present at a continuous suppression level. Different anaesthetics produce different BSPs indicating their different mechanisms of action. An algorithm for automatic detection of BSP was developed. Automatic detection is useful when comparing different anaesthetics at certain EEG effect level and when BSP level of anaesthesia is needed.