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Performance of Anesthetic Depth Indexes in Rabbits Under Propofol Anesthesia Prediction Probabilities and Concentration-Effect Relations

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Performance of Anesthetic Depth Indexes in Rabbits Under Propofol Anesthesia Prediction Probabilities and Concentration-Effect Relations Performance of Anesthetic Depth Indexes in Rabbits under Propofol Anesthesia Prediction Probabilities and Concentration-effect Relations Aura Silva, M.Sc.,* So´ nia Campos, M.Sc.,† Joaquim Monteiro, Ph.D.,‡ Carlos Venaˆ ncio, M.Sc.,* Bertinho Costa, Ph.D.,§ Paula Guedes de Pinho, Ph.D.,ʈ Luis Antunes, Ph.D.# Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/115/2/303/255162/0000542-201108000-00017.pdf by guest on 30 September 2021 ABSTRACT What We Already Know about This Topic • A number of electroencephalogram-based measures have Background: The permutation entropy, the approximate been studied to determine their usefulness for intraoperative entropy, and the index of consciousness are some of the most monitoring of anesthetic depth • recently studied electroencephalogram-derived indexes. In In rats anesthetized with a potent volatile anesthetic, burst suppression-corrected permutation entropy had the best cor- this work, a thorough comparison of these indexes was per- relation with anesthetic dose formed using propofol anesthesia in a rabbit model. Methods: Six rabbits were anesthetized with three propofol Ϫ Ϫ infusion rates: 70, 100, and 130 mg ⅐ kg 1 ⅐ h 1, each main- tained for 30 min, in a random order for each animal. What This Article Tells Us That Is New Data recording was performed in the awake animals 20, • In rabbits receiving propofol by infusion, burst suppression- 25, and 30 min after each infusion rate was begun in the corrected permutation entropy and burst suppression-cor- rected composite multiscale permutation entropy had the recovered animals and consisted of electroencephalogram best propofol concentration-effect relationships and predic- recordings, evaluation of depth of anesthesia according to a clinical tions of clinical signs scale, and arterial blood samples for plasma propofol determination. Median and spectral edge frequencies were analyzed for single-scale permutation entropy and composite multiscale permutation en- better prediction probabilities than did the other electroen- tropy, approximate entropy, index of consciousness, and the spec- cephalogram-derived parameters but not better than the tral parameters. The spectral parameters and single-scale and mul- electromyographic activity. tiscale permutation entropies were corrected for the presence of Conclusion: Single-scale and multiscale permutation entro- burst suppression. Performance of the indexes was compared by pies may be promising measures of propofol anesthetic depth prediction probability and pharmacodynamic analysis. when corrected for burst suppression. Additional studies should Results: The single-scale and composite multiscale permu- investigate the information measured by electromyography al- tation entropies with a burst suppression correction showed gorithms from commercial monitors of anesthetic depth. The rabbit may be a promising animal model for electroencephalo- * Doctoral Student, † Master’s Degree Student, Veterinary Sciences graphic studies because it provides a good-quality signal. Department, Universidade de Tra´s-os-Montes e Alto Douro, Via Real, Portugal. ‡ Researcher, ʈ Professor, REQUIMTE, Toxicology and Pharmacology Departments, Faculdade de Farma´cia da Universi- N recent years, the electroencephalogram has been ac- dade do Porto, Porto, Portugal. § Assistant Professor, Instituto Su- I tively studied for intraoperative monitoring of anesthetic perior Te´cnico, Universidade Te´cnica de Lisboa, Lisbon, Portugal. depth, resulting in a multitude of measures extracted from # Professor, Veterinary Sciences Department, Universidade de Trás-os- Montes e Alto Douro, and Researcher, Institute for Molecular and Cell this signal to translate it into a simple number. Biology, Porto, Portugal. Most recent parameters are based in nonlinear time series Received from the Veterinary Sciences Department, Universidade analysis, attempting to overcome limitations of older mea- de Tra´s-os-Montes e Alto Douro, Vila Real, Portugal. Submitted for sures based on the power spectrum.1,2 However, there is no publication August 3, 2010. Accepted for publication April 14, 2011. Supported by the Foundation for Science and Technology, Lisbon, consensus on the choice of the best parameter for clinical use. Portugal, under projects FCT PTDC/EEA-ACR/69288/2006, FCT PTDC/ Recently, permutation entropy (PE) was introduced and has CVT/101999/2008/COMPETE:FCOMP-01-0124-FEDER-009525, and FCT shown great potential because of ability to predict anesthetic PTDC/CVT/099022/2008/COMPETE:FCOMP-01-0124-FEDER-009497. concentration, high resistance to artifacts, and fast computa- Address correspondence to Dr. Silva: Quinta de Prados, Apartado 2 1013 5001-801 Vila Real, Portugal. [email protected]. Information on tion. It has been compared with approximate entropy (AE) purchasing reprints may be found at www.anesthesiology.org or on in patients receiving sevoflurane and propofol anesthesia and the masthead page at the beginning of this issue. ANESTHESIOLOGY’s has shown better results.1,2 PE has been further explored in a articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue. multiscale approach in an attempt to better understand Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott the dynamic characteristics of the electroencephalogram, Williams & Wilkins. Anesthesiology 2011; 115:303–14 resulting in composite multiscale permutation entropy Anesthesiology, V 115 • No 2 303 August 2011 Anesthetic Depth Indexes in Propofol Anesthetized Rabbits (CMSPE).3 Another recently studied measure is the index of Electroencephalographic Recording consciousness (IoC), the newest commercial monitor in this The electroencephalographic recordings were performed using context4,5; it is based in symbolic dynamics but, unlike the the IoC-View monitor (Aircraft Medical, Barcelona, Spain). PE, CMSPE, and AE, its exact calculation method is not Before induction of anesthesia, all of the animals’ heads totally revealed. Some limitations of PE, CMSPE, and AE were shaved, cleaned, and surface layers removed with fine have been discussed previously: the higher sensitivity to arti- sandpaper and acetone. Gel-coated, silver-silver chloride facts of AE and the difficulty of PE and CMSPE to detect electrodes (Swaromed, Innsbruck, Austria) were applied to burst suppression patterns in humans receiving sevoflurane record the electroencephalogram. Two electrodes (one for and propofol anesthesia.2,3,6 In a previous laboratory study, each eye) were placed 1 cm caudal to the lateral eye cantus; a central electrode was placed on the midline on the frontal the classic burst suppression correction could be applied suc- Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/115/2/303/255162/0000542-201108000-00017.pdf by guest on 30 September 2021 bone 3 cm from each previously applied electrode. This lo- cessfully to the PE in rats anesthetized with isoflurane, with ௡ better results than AE, IoC, and power spectrum-derived calization was based on previous works for the BIS monitor 10 parameters, median edge frequency (MEF) and spectral edge (Aspect Medical Systems, Newton, MA) in rabbits, which frequency 95 (SEF).7 has been determined to give the best quality electroenceph- Propofol is one of the most used hypnotics in clinical alographic signal after testing of different positions in pilot practice,8 and it is important to know its effects on these studies with the IoC-View Monitor (Morpheus-Medical, parameters, particularly to compare their performance at dif- Barcelona, Spain). ferent anesthetic depths achieved with the drug. This com- Impedance was automatically checked by the monitor and parison may benefit from the use of animal models because maintained at less than 15,000 ohms with a digitizing rate of 1,024 Hz. The electrodes were connected to the IoC-View such studies allow the comparison of parameter performance monitor, which was connected by Bluetooth® (Bluetooth SIG, in controlled conditions with reduced variability.9 In this Inc., Kirkland, WA) to a personal computer with the IoC-View context, the rabbit model shows great potential for transla- Graph software version 1.4 (Morpheus-Medical), a storage soft- tional research between animals and humans because of its ware provided by the manufacturer. small muscle layer between the skull and skin. We hypoth- esize that a rabbit model may allow the recording of an electroencephalographic signal with small electromyo- Anesthesia and Monitoring graphic contamination, which is important to guarantee After electroencephalogram baseline recording in the fully that brain effects, and not muscle tone, are being mea- awake animals for a period of 5 min, the fur on the ears was sured and reflected in the indexes. This is essential for clipped, the skin cleaned with alcohol, and a local analgesic future applications of the indexes in the electromyogra- cream was applied to the ear skin (EMLA; Nycomed US Inc, phy-rich human frontal montages and may contribute a Melville, NY). Thirty minutes later, two 22-gauge catheters rapid clarification on the potential use of different elec- were placed, one in the marginal ear vein and the other in the troencephalogram-derived indexes. central ear artery for arterial pressure monitoring. Both au- In the current study, the rabbit was used as a potential ricular catheter systems were flushed with heparinized saline translational research model for the comparison of clinical and fixed to the skin.
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