Spectral Entropy as a Measure of Hypnosis and Hypnotic Drug Effect of Total Intravenous Anesthesia in Children during Slow Induction and Maintenance

Background: We evaluated whether spectral entropy (SpE) can measure the depth of hypnosis and the hypnotic drug effect in children during total intravenous anesthesia. Methods: Sixty healthy children, aged 3–16 yr, were studied. Anesthesia was induced with an increasing target controlled infusion of propofol, and maintained by a stable remifentanil infusion and variable concentrations of target controlled infusion propofol. Depth of hypnosis was assessed according to the University of Michigan Sedation Scale (UMSS). Estimated plasma (Cp) and pseudo effect site (Ceff) propofol concentrations reflected the hypnotic drug effect. Patients were stratified to three age groups. The correlations between SpE versus UMSS, Cp, and Ceff were analyzed by Prediction Probability (Pk). The pharmacodynamic relationship between SpE and Cp, and the differences of SpE values between the age groups at the corresponding UMSS levels, were studied. Results: Respective mean Pk values for the youngest, middle, and oldest age groups were: 1) during induction: SpE versus UMSS 0.87, 0.87, and 0.93; SpE versus Cp 0.92, 0.95, and 0.97; and SpE versus Ceff 0.88, 0.94, and 0.95; 2) during maintenance: SpE versus Ceff 0.86, 0.75, and 0.81. The pharmacodynamic analysis determined an association between SpE and Cp that followed the Emax model closely. There were significant differences in SpE values between age groups at corresponding UMSS sedation levels. Conclusions: SpE measures the level of hypnosis and hypnotic drug effect in children during total intravenous anesthesia. There is an age dependency associated with SpE. Anesthesia should not be steered solely on the basis of SpE.

[1]  L. Senhadji,et al.  Variation of bispectral index under TIVA with propofol in a paediatric population. , 2008, British journal of anaesthesia.

[2]  K. Powers,et al.  Bispectral Index as a Guide for Titration of Propofol During Procedural Sedation Among Children , 2005, Pediatrics.

[3]  S. Shafer,et al.  'Intravenous Drug Delivery Systems' in Miller's Anesthesia , 2014 .

[4]  C. Deeprose,et al.  Awareness and memory function during paediatric anaesthesia. , 2008, British journal of anaesthesia.

[5]  K. Tremper,et al.  Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). , 2002, British journal of anaesthesia.

[6]  A. Davidson Monitoring the anaesthetic depth in children – an update , 2007, Current opinion in anaesthesiology.

[7]  Neonatal Exposure to a Combination of N-Methyl-d-aspartate and &ggr;-Aminobutyric Acid Type A Receptor Anesthetic Agents Potentiates Apoptotic Neurodegeneration and Persistent Behavioral Deficits , 2007 .

[8]  C. Rosow,et al.  Pediatric Evaluation of the Bispectral Index (BIS) Monitor and Correlation of BIS with End-tidal Sevoflurane Concentration in Infants and Children , 2000, Anesthesia and analgesia.

[9]  J. Dobbing,et al.  Comparative aspects of the brain growth spurt. , 1979, Early human development.

[10]  J. Olney,et al.  Early Exposure to Common Anesthetic Agents Causes Widespread Neurodegeneration in the Developing Rat Brain and Persistent Learning Deficits , 2003, The Journal of Neuroscience.

[11]  J. Olney,et al.  Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain , 2005, British journal of pharmacology.

[12]  T. Voepel-Lewis,et al.  The Incidence of Intraoperative Awareness in Children: Childhood Awareness and Recall Evaluation , 2009, Anesthesia and analgesia.

[13]  Warren D. Smith,et al.  Measuring the Performance of Anesthetic Depth Indicators , 1996, Anesthesiology.

[14]  J. Klockars,et al.  Spectral Entropy as a Measure of Hypnosis in Children , 2006, Anesthesiology.

[15]  D. Goodman,et al.  Plasma Concentration of Fentanyl, with 70% Nitrous Oxide, to Prevent Movement at Skin Incision , 1993, Anesthesiology.

[16]  T. Voepel-Lewis,et al.  Effect of Age and Sedative Agent on the Accuracy of Bispectral Index in Detecting Depth of Sedation in Children , 2007, Pediatrics.

[17]  B. Palanca,et al.  Association of Perioperative Risk Factors and Cumulative Duration of Low Bispectral Index with Intermediate-term Mortality after Cardiac Surgery in the B-Unaware Trial , 2010, Anesthesiology.

[18]  Fernando R Altermatt,et al.  Estimation of the Plasma Effect Site Equilibration Rate Constant (ke0) of Propofol in Children Using the Time to Peak Effect: Comparison with Adults , 2004, Anesthesiology.

[19]  M. Van der Linden,et al.  Intra‐operative awareness in children: the value of an interview adapted to their cognitive abilities , 2007, Anaesthesia.

[20]  Isabelle Murat,et al.  The Relationship Between Bispectral Index and Propofol During Target-Controlled Infusion Anesthesia: A Comparative Study Between Children and Young Adults , 2008, Anesthesia and analgesia.

[21]  G. H. Huang,et al.  Performance of entropy and Bispectral Index as measures of anaesthesia effect in children of different ages. , 2005, British journal of anaesthesia.

[22]  Andrew Forbes,et al.  The Effect of Bispectral Index Monitoring on Long-Term Survival in the B-Aware Trial , 2010, Anesthesia and analgesia.

[23]  Imke H. Bartelink,et al.  Guidelines on Paediatric Dosing on the Basis of Developmental Physiology and Pharmacokinetic Considerations , 2006, Clinical pharmacokinetics.

[24]  M. Watcha Investigations of the bispectral index monitor in pediatric anesthesia: first things first. , 2001, Anesthesia and analgesia.

[25]  P. Auinger,et al.  Additional Health Care Visits Needed Among Adolescents for Human Papillomavirus Vaccine Delivery Within Medical Homes: A National Study , 2007, Pediatrics.

[26]  Hee‐Soo Kim,et al.  Changes of bispectral index during recovery from general anesthesia with 2% propofol and remifentanil in children , 2007, Paediatric anaesthesia.

[27]  A. Yli-Hankala,et al.  Description of the Entropy™ algorithm as applied in the Datex‐Ohmeda S/5™ Entropy Module , 2004, Acta anaesthesiologica Scandinavica.

[28]  P. Laussen,et al.  The correlation of bispectral index with endtidal sevoflurane concentration and haemodynamic parameters in preschoolers , 2002, Paediatric anaesthesia.

[29]  L Senhadji,et al.  Impact of age on both BIS values and EEG bispectrum during anaesthesia with sevoflurane in children. , 2005, British journal of anaesthesia.

[30]  H. Kim,et al.  Correlation of bispectral index with end-tidal sevoflurane concentration and age in infants and children. , 2005, British journal of anaesthesia.

[31]  Entropy and Bispectral Index during Anaesthesia in Children , 2004, Anaesthesia and intensive care.

[32]  L Senhadji,et al.  The impact of age on bispectral index values and EEG bispectrum during anaesthesia with desflurane and halothane in children. , 2006, British journal of anaesthesia.

[33]  B. Anderson Pediatric models for adult target‐controlled infusion pumps , 2010, Paediatric anaesthesia.

[34]  Hugo Vereecke,et al.  Spectral Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect: A Comparison with Bispectral Index and Processed Midlatency Auditory Evoked Response , 2004, Anesthesiology.

[35]  J. Sigl,et al.  Anesthesia awareness and the bispectral index. , 2008, The New England journal of medicine.

[36]  Sinikka Münte,et al.  The Narcotrend Index Indicates Age-Related Changes During Propofol Induction in Children , 2009, Anesthesia and analgesia.

[37]  D. Tibboel,et al.  Intraoperative awareness during paediatric anaesthesia. , 2009, British journal of anaesthesia.

[38]  R. Sethuraman Chapter 133 – Intravenous Drug Delivery Systems , 2007 .

[39]  E Olofsen,et al.  Propofol Anesthesia and Rational Opioid Selection: Determination of Optimal EC50‐EC95 Propofol‐Opioid Concentrations that Assure Adequate Anesthesia and a Rapid Return of Consciousness , 1997, Anesthesiology.

[40]  Kris Jamsen,et al.  Awareness During Anesthesia in Children: A Prospective Cohort Study , 2005, Anesthesia and analgesia.

[41]  Fredrik Granath,et al.  Mortality Within 2 Years After Surgery in Relation to Low Intraoperative Bispectral Index Values and Preexisting Malignant Disease , 2009, Anesthesia and analgesia.

[42]  I. Constant,et al.  Which model for propofol TCI in children , 2010, Paediatric anaesthesia.

[43]  Jeffrey C. Sigl,et al.  Anesthetic Management and One-Year Mortality After Noncardiac Surgery , 2005, Anesthesia and analgesia.

[44]  H. Lilliefors On the Kolmogorov-Smirnov Test for Normality with Mean and Variance Unknown , 1967 .

[45]  H F Nicodemus,et al.  The Pharmacokinetics of Propofol in Children Using Three Different Data Analysis Approaches , 1994, Anesthesiology.

[46]  H. Muñoz,et al.  Effect site concentrations of propofol producing hypnosis in children and adults: comparison using the bispectral index , 2006, Acta anaesthesiologica Scandinavica.

[47]  A. Hill,et al.  The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves , 1910 .

[48]  H Schwilden,et al.  Pharmacodynamic modelling of the bispectral index response to propofol-based anaesthesia during general surgery in children. , 2008, British journal of anaesthesia.