REVIEW Electroencephalogram-based depth of anaesthesia measurement: Combining opioids with hypnotics Jukka Kortelainen * , Tapio Seppänen Department of Computer Science and Engineering, University of Oulu, Oulu, Finland Keywords: BIS Depth of anaesthesia EEG Monitoring Opioid summary Within the last few decades, the electroencephalogram has become a widely used tool for the automatic assessment of depth of anaesthesia. The method has, however, faced some significant challenges. One of these is that many different classes of anaesthetic drugs, all of which affect the electroencephalogram, are used nowadays simultaneously during operations. Especially, the assessment of depth of anaesthesia induced by combining opioids with hypnotics has been raised as one of the major problems in the field and a large body of literature dealing with this topic has been published. The problem is addressed in this review. After giving an overview of the electroencephalogram and derived computational parameters during anaesthesia, the paper focuses on presenting the relevant literature related to the depth of anaesthesia measurement during hypnoticeopioid anaesthesia. The main findings are summarized and suggestions for the electroencephalogram-based depth of anaesthesia assessment in the clinical envi- ronment as well as future research are given. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Ever since the invention of general anaesthesia, the measure- ment of its depth has provided a challenge for the clinicians. While too deep anaesthesia leads to numerous complications, such as haemodynamic instability and prolonged recovery, too light anaesthesia has distressing consequences from the patient’s point of view as well. The classic approach to assess the anaesthetic state has been to observe the patient’s clinical signs (e.g. a response to a verbal command or reaction to a painful stimulation). Later, alter- native ways, such as the estimation of drug concentration in the exhaled gas or in the blood using mathematical models, have been proposed for the approximation of the effect of anaesthetic drugs. Already in the early 20th century, electroencephalogram (EEG), the measurement of the electrical activity of the brain, was shown to react to the administration of anaesthetic drugs. 1,2 The findings spawned a whole branch of research investigating the relationship between EEG changes and the depth of anaesthesia. The advantage of this approach is that EEG is a direct measurement from the main effect-site of anaesthetics, the brain. However, it was not before the late 1990s that the technological development made the automatic assessment of depth of anaesthesia possible. The first commercial monitor, Bispectral Index, approved by the FDA for this purpose was introduced in 1996 by Aspect Medical Systems. Soon after the introduction of Bispectral Index, several other commercial indices were launched. The EEG-based depth of anaesthesia measurement has been associated with a decreased incidence of intraoperative awareness and recall, 3,4 faster recovery, 5e9 and reduced post- operative vomiting. 10 In addition, the monitoring reduces the con- sumption of anaesthetics. 6,9,11,12 The EEG-based depth of anaesthesia measurement has faced, however, some significant challenges. One of these is that many different classes of anaesthetic drugs, all of which affect EEG, are used nowadays simultaneously during operations. Especially, the assessment of depth of multidrug anaesthesia induced by combining opioids with hypnotic agents has been raised as one of the major problems in the field and a large body of literature dealing with this topic has been published. The purpose of this paper is to provide a comprehensive review of these publications. Based on the main findings in the literature, suggestions for the EEG-based depth of anaesthesia assessment in the clinical envi- ronment as well as future research are given. Before this, an overview of the EEG and derived computational parameters dur- ing anaesthesia is presented. The material presented is based on the first author’s Ph.D. thesis 13 and is published with permission of Acta Universitatis Ouluensis. The figures are constructed from the dataset described in detail in the authors’ previous publication. 14 * Corresponding author. Department of Computer Science and Engineering, BOX 4500, FIN-90014, University of Oulu, Finland. Tel.: þ358 29 4488048; fax: þ358 8 5532612. E-mail address: jukortel@ee.oulu.fi (J. Kortelainen). Contents lists available at SciVerse ScienceDirect Trends in Anaesthesia and Critical Care journal homepage: www.elsevier.com/locate/tacc 2210-8440/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tacc.2013.03.009 Trends in Anaesthesia and Critical Care 3 (2013) 270e278