Electroencephalography in anaesthesia; opening minds to the future

Sepúlveda, P.O.; Naranjo, M.
doi:10.1016/j.redare.2018.11.008
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Adequate anaesthesia to perform a surgical procedure has long been a matter of discussion&#46; The first attempts to classify anaesthesia were made by Guedel in 1920 and Lundi in the 1930s&#46; In 1968&#44; pharmacological definitions were introduced that are still in use today&#44; such as the minimum alveolar concentration&#44; which is defined by immobility in response to pain stimulus&#46; These concepts were reasonable in surgical scenarios in which the main focus was placed on monitoring vital parameters to avoid hypoxia and hypotension&#46; Brain monitoring&#44; nonexistent at that time&#44; was based on maintaining haemodynamic balance and immobility to facilitate the performance of the surgical procedure&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In the early 1990s&#44; Rampil et al&#46; demonstrated the spinal cord original of minimum alveolar concentration by showing that the concentration needed to prevent movement response to stimulus remained the same&#44; even in an experimental group of decerebrated rats&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">This proved that movement response &#40;both motor and haemodynamic&#41; depends mainly on subcortical control&#46; However&#44; loss of consciousness is more a phenomenon of cortical and thalamocortical pathways&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">This notion&#44; however&#44; has taken some time to translate into clinical practice&#46; Indeed&#44; the very clinical concept of anaesthesia depth has been a source of confusion&#46; Often considered a single phenomenon&#44; only after much effort have clinicians been able to differentiate between cortical and subcortical components&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">This has been due to a poor understanding of the different brain circuits associated with consciousness or those that affect nociceptive pathways&#46; It was necessary to combine concepts of neurophysiology&#44; neuroanatomy and neuropharmacology in order to advance in the understanding of what we observe as electrophysiological phenomena in the EEG&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">An obvious example of the lack of understanding of this concept has been the exclusive use of inhaled anaesthetic agents&#44; where prioritising the clinical concept of immobility led to anaesthesia with significant cortical activity depression&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Misunderstandings in the clinical definition of loss of consciousness or loss of response has so far led to incorrect clinical strategies&#44; such as correcting the haemodynamic response by changing the concentration of the hypnotic drug&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Sanders et al&#46; defined consciousness as a subjective perceptual experience&#44; differentiating it from the concept of connection with the surroundings and capacity to respond to stimuli&#46; Loss of connection is used in this case as a decrease in cortical input from the senses or endogenous information&#46; This is a subcortical phenomenon caused by so-called &#8220;thalamic gating or gating of other core nuclei&#8221;&#44; which occurs when efferents towards the cortex are blocked&#44; generating a semi anti-nociceptive state&#46; The loss responsiveness is the lack of response to stimulus&#44; a phenomenon that can occur even while maintaining certain levels of consciousness&#44; as occurs with the exclusive use of high-dose opioids&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In an elegant multicentre study&#44; Sebel et al&#46; showed clearly how the bispectral index &#40;BIS&#41; was able to differentiate between use of subcortical and cortical drugs&#44; with the latter affecting the BIS level&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Loss of responsiveness cannot be interpreted as unconsciousness&#46; This was recently demonstrated by Radek et al&#46; who concluded that patients aroused during continual TCI perfusion of propofol or dexmedetomidine&#44; titrated to the threshold of loss of responsiveness&#44; tended to report experiences from the unresponsive period prior to unconsciousness&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">On the other hand&#44; from the pharmacological point of view&#44; models that correlate effect with plasma concentrations have been&#44; to a certain extent&#44; useful for guiding titration&#46; Most such models were constructed in unstable mixtures with boluses or rapid infusions&#44; and propose that the plasma-effect gap could simply be assumed to be in equilibrium using a mathematical device that collapsed that gap &#40;hysteresis collapse&#41;&#46; As a result &#8220;site effect&#8221; models are associated with overestimation&#44; and anaesthesiologists using them tend to overdose&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The introduction of the EEG in 1937<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> prompted attempts to identify markers of unconsciousness that could guide anaesthesia&#46; However&#44; the inability to do online analysis and the limited capacity of computers at the time forced clinicians to look for simplifying solutions&#46; Added to this was the fact anaesthesiologists&#44; who were able interpret ECGs&#44; were not trained in reading EEG&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">EEG studies soon showed that apart from slowing overall cortical activity&#44; administration of anaesthetics was associated with a marked anterior shift in alpha activity &#40;7&#8211;12<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#8211;8</span></a> This was used in the BIS<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> algorithm&#44; giving the anaesthesiologist a simple solution that reduced the risk of intraoperative awakening &#40;explicit recall&#41;&#46; The indices created at that time involve simplified frontal lobe activity processes&#44; which correlate frequency analysis &#40;alpha&#44; beta or burst suppression ratios&#44; <span class="elsevierStyleItalic">etc&#46;</span>&#41; with clinical states and&#47;or drug concentrations using different estimation techniques &#40;for example&#44; diffuse logic&#41;&#46; These indices&#44; therefore&#44; are the product of complex statistics that assume that all anaesthetics generate the same electroencephalographic behavioural condition&#44; and that do not include age as a covariate&#46; In addition&#44; they are associated with processing delays and reactions that differ at induction and emerge from anaesthesia&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">We now know that age does impact EEG electrical activity<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a> and response to anaesthesia&#44; and that each anaesthetic has its own particular electroencephalographic signature&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> Unfortunately&#44; the objective of reducing the frequency of explicit intraoperative arousal was not achieved&#44; and the research focused solely on high-risk populations&#44; where predictive pharmacological models are even poorer in data&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In the search for more representative mechanisms of the phenomenon of unconsciousness&#44; a monitor was developed based on auditory evoked potentials&#46; Schraag et al&#46; showed that auditory evoked potentials were somewhat better than BIS at predicting unconsciousness&#44; defined electrically as the appearance of 2 waves &#40;P1 and N2&#41; in mid latency evoked potentials that reflected the slowing down of activity from the geniculate body and the primary auditory cortex&#46; This slowdown partially represents loss of the arousal required to regain consciousness&#44; but late corticocortical potentials were already greatly diminished&#44; creating an &#8220;excess&#8221; in that territory and the subsequent reconnection capacity of the cognitive processes&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">This monitor met with little success because it was an &#8220;all or nothing&#8221; measure of unconsciousness&#44; and there was no linearity with plasma concentrations that is required in the administration of sedation&#46; Moreover&#44; the signal was extracted from subcortical activity and was&#44; therefore&#44; far from the corticocortical evaluation needed to identify the phenomenon of unconsciousness in earlier stages&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The article by Ferreira et al&#46; in this issue of the <span class="elsevierStyleSmallCaps">Spanish Journal of Anaesthesiology and Critical Care</span><a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> is an attempt to systematise the EEG indices associated with clinical unconsciousness for anaesthesia&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">It clearly shows that an index that simplifies cortical activity&#44; associated with the immense variability of each monitor&#44; is incapable of fully describing the phenomenon of anaesthesia&#46; A simple exercise involves predicting the moment of the loss of clinical consciousness solely by observing the index&#59; this&#44; in the vast majority of cases&#44; fails&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">One reason for the low predictive power and great variability in response observed in these monitors may be the tendency to assume unproven paradigms&#44; such as&#44; for example&#44; the linearity of plasma concentration effect&#46; We now have evidence that multiple dynamic &#40;behavioural&#41; states lurk under the mantle of unconsciousness&#44; and that these do not necessarily follow a linear pattern in a wide range of drug concentrations&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">With respect to potential markers for future development&#44; studies such as that published by Jordan et al&#46;&#44; which reports that propofol-induced unconsciousness is associated with a reduction in lateral anteroposterior frontoparietal directional connectivity&#44; which also involves the region of the insula&#46; The authors used a high-density EEG and a magnetic resonance technique called symbolic transfer entropy&#44; based on information theory&#44; to show that this loss of electric flow is aloss-of-feedback phenomenon that is particularly important in the generation of human consciousness&#46; It is striking to note that this is a common phenomenon in gabaergic or ketamine-based anaesthesia&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> Recent <span class="elsevierStyleItalic">in vitro</span> studies have uncovered other&#44; more specific&#44; unconsciousness markers for propofol&#44; such as a peak-max alpha wave&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Other challenges facing brain monitor development is to show neurophysiological states where there is no doubt that the patient is incapable of generating consciousness&#46; We get a glimpse of this today in monitors that show a monotonous spectrogram with alpha and delta bands for gabaergic drugs&#44; associated with SEF95 spectral frequencies under 15<span class="elsevierStyleHsp" style=""></span>Hz in healthy adults&#44; slightly higher in children&#44; or more compressed in older individuals&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">These new monitors should also be capable of early identification of drug overdosing&#44; before the appearance of the burst-suppression ratio&#46; The phenomenon of burst-suppression&#44; which does not depend exclusively on drug overdosing&#44; is particularly challenging because of its complexity&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In our opinion&#44; the greatest challenge involves controlling anaesthesia overdosing&#46; Although this is poorly defined&#44; some clinical estimates suggest that it occurs in up to 40&#37; of cases&#44; even in groups that regularly use BIS monitoring&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Anaesthesiologists encounter an increasing number of elderly patients with particularly frail brains&#46; This must compel us to improve our understanding of specific brain dynamics during anaesthesia in order to facilitate physiological reconnection and recovery of the connectivity of the state of consciousness&#44; and thus reduce postoperative delirium rates and other potentially chronic cognitive alterations&#46; The authors of a recent study propose diagnosing brain frailty on the basis of the speed of onset of slow-wave saturation&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Speculating that the assumed linearity between plasma concentration and the depressive effect of anaesthesia does not exist&#44; the complexity of non-physiological phenomena such as burst-suppression shows that the task of identifying the adequate anaesthetic unconsciousness is still very challenging&#46;</p></span>"
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