EEG‐based monitor on anti‐nociception during general anaesthesia: mission impossible?

General anaesthesia is a drug-induced state of unconsciousness and anti-nociception, eventually with peripheral neuromuscular block added. Up to the end of the last century, clinical signs were the only tokens of monitoring the central nervous system (CNS) effects, whereas peripheral muscular function was easily available for objective and precise monitoring. One problem of CNS monitoring has to do with the diversity of anaesthetic drug effects on a variety of receptors and neural networks. Also, the general complexity of the numerous responses from the CNS, some endogenous and some drug induced, are not readily measurable as clear-cut and linear responses. Still, the state of unconsciousness from the GABA-ergic hypnotics and the potent volatiles is fairly readily mirrored in the EEG signals of the cerebral cortex in an unstimulated patient, although the EEG patterns for drugs like ketamine and nitrous oxide are hard to elucidate. Different monitors such as BIS, Entropy, Narcotrend and auditory evoked potential (AEP) are in regular clinical use with documented effects of more focused and reduced drug dosing, and documented for BIS: less awareness. Monitoring the anti-nociceptive drug effect is useful because a sudden and strong nociceptive stimulus may result in untoward autonomic responses and muscular reflex movements. Unopposed stimulation may also ‘overrule’ a state of stable unconsciousness, with resultant awakening and awareness. The traditional clinical use of systolic or mean blood pressure is actually still one of the best methods in everyday use for this monitoring purpose. Another cornerstone is the experience of which drugs and doses are effective in attenuating nociception. Alpiger and colleagues found that simple end-tidal monitoring of sevoflurane was a better predictor of nociceptive response than AEP. Thus, monitoring the state of anti-nociception with objective, non-clinical methods is still in a state of testing and development, without welldocumented and proven methods for consistent ‘no-fuss’ clinical daily use. Some methods, like those using systolic blood pressure, are based on the reduced sympathetic response from the CNS when in a state of drug-induced anti-nociception during concomitant surgical stress. These include the pulse plethysmogram amplitude, heart rate variability and/or amplitude, pupillometry, muscle tonus and skin conductance. They all have limitations in interpretation, as the state of sympathetic tone is strongly influenced by numerous factors, including hypovolaemia, vasopressors, atropine and patient positioning. In addition, sympathetic tone is very unspecific in the awake or lightly sedated patient, as mood and subjective feelings have a strong impact. Attempts are also been made on using the EEG for monitoring of anti-nociception. This approach has been challenged as futile, as most of the antinociceptive drugs effects are in the periphery, the medullary cord or deeper cerebral layers, far from the EEG signals derived from the frontal cortex. Still, proponents will argue that the EEG is a ‘mirror’ of what is going on in other parts of the CNS and peripheral nervous system. One problem is to elucidate how the EEG signals may be used in a sensitive and specific way to reflect anti-nociception. Concepts such as response-entropy, Composite Variability Index and BIS variability score have been tested and launched with limited success, so far.