Stefan Schraag, MD
Department of Anaesthesiology
University of Ulm, Germany
Why monitor the central
nervous system ?
Obviously, all of us have gotten along without any monitor until now, so why should we bother? The practice of anaesthesia remains one of the safest and most effective in medicine. Furthermore, like all new technologies, CNS monitoring devices will add something to the cost of delivering anaesthesia. On the other hand, there is no doubt, that significant unpredictability and uncertainty still exists in the delivery of anaesthetic drugs. This is reflected in the variety of suggested dosing regimens, especially in intravenous anaesthesia. Some patients still suffer intra-operative awareness and may consecutively develop posttraumatic stress disorder [1], whereas others still have prolonged recovery due to relative overdosing even with otherwise short-acting drugs. The primary reason for using any monitor designed to reflect the anaesthetic state must be to improve patient care.
This lecture will give an overview of current methodology using the auditory evoked response and its impact on both research and clinical anaesthesia.
What is the rationale the auditory evoked response?
Adequate oblivion is a requirement and expectation of patients undergoing general anaesthesia. The main target of drugs used in general anaesthesia is the central nervous system and therefore a reliable signal produced in the CNS is required, which reflects the balance of increasing concentrations of general anaesthetics on one hand and the nociceptive stimulation response produced by surgery on the other. Evoked potentials are the non-random components of the electroencephalogram which follow a brief sensory stimulus. Of particular interest in the monitoring of the anaesthetic effect are the early cortical responses to auditory stimuli (mid-latency auditory evoked responses), which have been shown to be extremely consistent in terms of different anaesthetic drugs and increasing drug concentrations of these drugs, with the exception of Ketamine and Benzodiazepines [2]. Processing of AEP biosignals usually consist of
1.
signal
acquisition
2.
signal
transformation
3. parameter selection
4. signal classification.
In this context a couple of approaches have been successfully studied to describe an index or parameter based on the auditory evoked response, such as the auditory evoked potential index (AEPex) [3], the autoregressive adaptive modelling (AAI) [4], Forty-hertz midlatency auditory evoked potential activity [5] or wavelet analysis of middle latency auditory evoked responses [6]. One of the problems with using evoked potentials for monitoring is the small size of the bioelectric signal, necessitating a prolonged period of averaging between measurements. However, the key issue in AEP monitoring remains the quality of the primary signal presented to subsequent processing and analysis.
Which clinical benefits does the
auditory evoked response provide?
During the last decade, there has been a large number of studies, which tried to validate the AEP in the context of clinical anaesthesia. Although they were evaluated in a variety of clinical situations and with different drugs and drug combinations, their results appear, with only a few exceptions [7], quite consistent. The essence is, that in comparison with other electrophysiological variables, auditory evoked potentials both better indicate the arousability of a patient in response to stimulation and better discriminate the transition from consciousness to unconsciousness and vice versa [8,9], whereas processed measures of the EEG, like the bispectral index (BIS), are better correlated with increasing drug concentrations [10]. This lets us suggest, that both measures are valuable, but reflect different functional parts of the cortico-thalamic neuraxis.
How can auditory evoked potentials be
used to improve research ?
The evolution of quantitative monitors of “hypnosis” tempts one to consider automated control of anaesthetic administration. Closed-loop control of anaesthesia has awaited the development of a sufficiently robust monitor. New designs for automated anaesthetic administration have been successfully evaluated using mid-latency auditory evoked potentials as the input signal [11]. These systems are able to provide an unbiased control method of anaesthesia effect when used in pharmacodynamic studies [12]. Furthermore, results of interaction studies utilizing AEP have revealed more insight into the quantitative contribution of opioids to general anaesthesia and hypnosis [13, 14] and have supported some physiological processes. It is now highly evident that the degree of AEP suppression reflects increasing levels of unconsciousness and amnesia produced by hypnotic anaesthetics, whereas other states of unresponsiveness, such as the effect of higher opioid concentrations is less good represented by changes in AEP [15].
Conclusion
In summary, recent developments in AEP monitoring have contributed to an increasing predictability and safety of titrating general anaesthetics. The AEP signal is one of most robust and universally applicable measure to quantify concentration-effect responses of anaesthetic drugs and is therefore suitable to act as an unbiased calibration tool in pharmacodynamic research. Although predominantly used in experimental settings yet, a first commercially available AEP device is now undergoing clinical validation studies [16]. Whereas AEP monitoring will definitely contribute to an improved patient care by the anaesthetist, its potential to detect and subsequently avoid intraoperative memory formation and recall remains to be demonstrated [17].
Selected
recommended references:
1.
Sandin RH,
Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a
prospective case study. Lancet 2000; 355:707-11.
2.
Thornton C,
Sharpe RM. Evoked responses in anaesthesia. Br J Anaesth 1998; 81:771-81.
3.
Mantzaridis H, Kenny GNC. Auditory
evoked potential index: A quantitative measure of changes in auditory evoked
potentials during general anaesthesia. Anaesthesia 1997; 52:1030-6.
4.
Jensen EW, Lindholm P, Henneberg SW. Autoregressive modelling with exogenous input of
auditory evoked potentials to produce an online depth of anaesthesia index.
Methods Inform Med 1996; 35:256-60.
5.
Dutton RC, Smith
WD, Rampil IJ, Chortkoff BS, Eger EI II. Forty-hertz midlatency auditory evoked
potential activity predicts wakeful response during desflurane and propofol
anesthesia. Anesthesiology 1999; 91:1209-20.
6.
Kochs E,
Stockmanns G, Thornton C, Nahm W, Kalkman CJ. Wavelet analysis of middle
latency auditory evoked responses. Anesthesiology 2001; 95:1141-50.
7.
Kochs E,
Kalkman CJ, Thornton C, Newton D, Bischof P, Kuppe H, Abke J, Konecny E, Nahm
W, Stockmanns G. Middle latency auditory evoked responses and electroencephalographic
derived variables do not predict movement to noxious stimulation during 1
minimum alveolar anesthetic concentration isoflurane/nitrous oxide anesthesia.
Anesth Analg 1999; 88:1412-7.
8.
Kurita T, Doi
M, Sano H, Sato S, Mantzaridis H, Kenny GNC. Auditory evoked potential index
predicts the depth of sedation and movement in response to skin incision during
sevoflurane anesthesia. Anesthesiology 2001; 95; 364-70.
9.
Schraag S,
Bothner U, Gajraj RJ, Kenny GNC, Georgieff M. The performance of electroencephalogram
bispectral index and auditory evoked potential index to predict loss of
consciousness during propofol infusion. Anesth Analg 1999; 89:1311-5.
10.
Doi M, Gajraj
RJ, Mantzaridis H, Kenny GNC. Prediction of movement at laryngeal mask
insertion: comparison of auditory evoked potential index, bispectral index,
spectral edge frequency and median frequency. Br J Anaesth 1999; 82:203-7.
11.
Kenny GNC,
Mantzaridis H. Closed loop control of anaesthesia. Br J Anaesth 1999; 83:223-8.
12.
Bothner U,
Milne S, Kenny GNC, Georgieff M, Schraag S. Bayesian probabilistic network
modeling of remifentanil and propofol interaction on wakeup time after
closed-loop controlled anesthesia. Int J Clin Monit 2002 (in press).
13.
Iselin-Chaves
IA, El Moalem HE, Gan TJ, Ginsberg B, Glass PSA. Changes in the auditory evoked
potentials and the bispectral index following propofol or propofol and
alfentanil. Anesthesiology 2000; 92:1300-10.
14.
Crabb I,
Thornton C, Konieczko KM, Aquilina R, Frazer N, Doré CJ, Newton DEF.
Remifentanil reduces auditory and somatosensory evoked responses during
isoflurane anaesthesia in a dose-dependent manner. Br J Anaesth 1996; 76:795-801.
15.
Schraag
S, Schleyer M, Flaschar J, Georgieff M.
Quantitative contribution of remifentanil to middle latency auditory evoked
potentials during closed-loop propofol anaesthesia. Br J Anaesth 1999; 82:A.397.
16.
Welschbillig
S, Plantade N, Martinon C, Hentgen E, Billard V. Performance of the AAI Index
of AEP to predict loss of consciousness during propofol anesthesia.
Anesthesiology 2001; 95:A-565.
17.
Loveman E,
Van Hooff JC, Smith DC. The auditory evoked response as an awareness monitor
during anaesthesia. Br J Anaesth 2001; 86:513-8.