Novel neurophysiological monitors of the transition from wakefulness to loss of consciousness during anaesthesia

Abstract: Background: The concept of adequate anaesthesia is not easily defined. One important component of anaesthesia is the suppression of wakefulness, that is, a patient who does not experience sensory input such as hearing, vision, and feeling of pain. The ability to determine the depth of anaesthesia for an individual patient is of great clinical value. Optimally, the clinician would like to avoid both excessively deep and superficial anaesthesia. Furthermore, this judgement needs to be made in real time - not after the fact. The transition between being fully awake and loss of consciousness should be clinically definable, as well as the ability to predict if the patient is going to react at the start of surgical stimulation. The studies included in this dissertation summary have focused on the possibility to objectively define and measure the transition between wakefulness and loss of consciousness in real time using commercially available monitors of anaesthetic depth based on neurophysiological principals. Both of the two monitors studied transform the electroencephalogram (EEG) to a simple numerical index. Bispectal analysis of the passive EEG yields the bispectral index (BIS) while the AAI index reflects the EEG effect of an auditory stimulation on the EEG. Study 1 investigated the effect of an established intravenous anaesthetic technique based on fentanyl (opiate) and midazolam (bensodiazepam) on BIS and how well BIS reflected the degree of wakefulness. Plasma concentrations of the anaesthetics and awareness of a loud auditory stimulus were evaluated. Study 2 investigated how nitrous oxide influenced BIS and how well BIS could distinguish between wakefulness and loss of consciousness with nitrous oxide. Nitrous oxide was administered both as a sole anaesthetic and as an adjunct to an intravenous anaesthetic. The effect of the anaesthetic gas sevoflurane on BIS was also studied as an active reference. Study 3 investigated the influence of the fentanyl alone on BIS. Studies 4 and 5 investigated how the hypnotic drug propofol influenced BIS and how well BIS could distinguish between wakefulness and unconsciousness. The anaesthetic depth AAI -index based on the auditory evoked potential was also studied and compared with BIS. Results: Study 1 BIS was very variable during intravenous anaesthesia based on fentanyl and midazolam. Despite the registration of high BIS values on several occasions, no patient reported either explicit or implicit awareness during anaesthesia nor of the auditory stimulus. The loud auditory stimulus used for auditory evoked potential gave no increase in BIS. Plasma concentrations of fentanyl and midazolam. did not correlate with BIS. Study 2 The addition of nitrous oxide to an intravenous anaesthesia did not influence BIS. BIS was not influenced by nitrous oxide when used to render volunteers unconscious. BIS decreased in a regular fashion with increasing sevoflurane concentration. Study 3 A wide range of BIS values were seen when fentanyl alone was given. High BIS values were seen in patients made unconscious during anaesthetic induction using fentanyl after only a small dose propofol. Study 4 BIS decreased during propofol induction but varied widely at the transition between wakefulness and loss of consciousness. Study 5 The auditory evoked potential index AAI decreased during propofol induction but in a more on-off fashion than BIS and at a wide range of values at the transition to loss of consciousness. Summary: The two commercial monitors studied here are potential complements to the clinical assessment of depth of anaesthesia. BIS decreased with increasing depth of hypnosis but with a distinct variation between different anaesthetics. No threshold value for either BIS or AAI could be found which for the individual patient could reliably predict the transition between wakefulness and unconsciousness in real time.