Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl


The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 μg/kg (fentanyl low dose, FLD) or 24 μg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. 1.

    Bruhn J, Myles PS, Sneyd R, Struys MMRF. Depth of anaesthesia monitoring: what’s available, what’s validated and what’s next? Br J Anaesth. 2006;97(1):85–94.

  2. 2.

    Velly LJ, Rey MF, Bruder NJ, Gouvitsos FA, Witjas T, Regis JM, Peragut JC, Gouin FM. Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia. Anesthesiology. 2007;107(2):202–12.

  3. 3.

    Xie G, Deschamps A, Backman SB, Fiset P, Chartrand D, Dagher A, Plourde G. Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study. Br J Anaesth. 2011;106(4):548–57.

  4. 4.

    Jäntti MDPDV, Heikkinen MDPDE, Alahuhta MDPDS, Remes RNR, Suominen PLK. Cortical electroencephalogram from subcortical electrodes rather than electrosubcorticogram. Anesthesiology. 2008;108(5):963–4. doi:10.1097/ALN.0b013e31816bbdcf.

  5. 5.

    Rey MF, Velly LJ, Bruder NJ. Cortical electroencephalogram from subcortical electrodes rather than electrosubcorticogram. Anesthesiology. 2008;108(5):964–5. doi:10.1097/01.anes.0000311151.85247.f3.

  6. 6.

    Bonhomme V, Fiset P, Meuret P, Backman S, Plourde G, Paus T, Bushnell MC, Evans AC. Propofol anesthesia and cerebral blood flow changes elicited by vibrotactile stimulation: a positron emission tomography study. J Neurophysiol. 2001;85(3):1299–308.

  7. 7.

    Lydic R, Baghdoyan HA. Sleep, anesthesiology, and the neurobiology of arousal state control. Anesthesiology. 2005;103(6):1268–95.

  8. 8.

    Bergmann I, Göhner A, Crozier TA, Hesjedal B, Wiese CH, Popov AF, Bauer M, Hinz JM. Surgical pleth index-guided remifentanil administration reduces remifentanil and propofol consumption and shortens recovery times in outpatient anaesthesia. Br J Anaesth. 2013;110(4):622–8.

  9. 9.

    Lobo FA, Schraag S. Limitations of anaesthesia depth monitoring. Curr Opin Anesthesiol. 2011;24(6):657–64.

  10. 10.

    Sleigh JW, Sanders RD. Intraoperative analgesic titration: the hunting of the snark. Anesth Analg. 2014;119(2):234–6.

  11. 11.

    Bouillon TW, Bruhn J, Radulescu L, Andresen C, Shafer TJ, Cohane C, Shafer SL. Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy. Anesthesiology. 2004;100(6):1353–72.

  12. 12.

    Kortelainen J, Koskinen M, Mustola S, Seppanen T. Effects of remifentanil on the spectrum and quantitative parameters of electroencephalogram in propofol anesthesia. Anesthesiology. 2009;111(3):574–83.

  13. 13.

    Huiku M, Uutela K, van Gils M, Korhonen I, Kymäläinen M, Meriläinen P, Paloheimo M, Rantanen M, Takala P, Viertiö-Oja H, Yli-Hankala A. Assessment of surgical stress during general anaesthesia. Br J Anaesth. 2007;98(4):447–55.

  14. 14.

    Struys MMRF, Vanpeteghem C, Huiku M, Uutela K, Blyaert NBK, Mortier EP. Changes in a surgical stress index in response to standardized pain stimuli during propofol–remifentanil infusion. Br J Anaesth. 2007;99(3):359–67.

  15. 15.

    Gruenewald M, Meybohm P, Ilies C, Hocker J, Hanss R, Scholz J, Bein B. Influence of different remifentanil concentrations on the performance of the surgical stress index to detect a standardized painful stimulus during sevoflurane anaesthesia. Br J Anaesth. 2009;103(4):586–93.

  16. 16.

    Mathews DM, Clark L, Johansen J, Matute E, Seshagiri CV. Increases in electroencephalogram and electromyogram variability are associated with an increased incidence of intraoperative somatic response. Anesth Analg. 2012;114(4):759–70.

  17. 17.

    Ellerkmann RK, Grass A, Hoeft A, Soehle M. The response of the composite variability index to a standardized noxious stimulus during propofol-remifentanil anesthesia. Anesth Analg. 2013;116(3):580–8.

  18. 18.

    Bojak I, Liley DTJ. Modeling the effects of anesthesia on the electroencephalogram. Phys Rev E. 2005;71(4):041902.

  19. 19.

    Liley DTJ, Cadusch PJ, Dafilis MP. A spatially continuous mean field theory of electrocortical activity. Netw Comput Neural. 2002;13(1):67–113.

  20. 20.

    Liley DT, Cadusch PJ, Gray M, Nathan PJ. Drug-induced modification of the system properties associated with spontaneous human electroencephalographic activity. Phys Rev E. 2003;68:051906.

  21. 21.

    Liley DT, Bojak I. Understanding the transition to seizure by modeling the epileptiform activity of general anesthetic agents. J Clin Neurophysiol. 2005;22(5):300–13.

  22. 22.

    Steyn-Ross ML, Steyn-Ross DA, Sleigh JW, Liley DTJ. Theoretical electroencephalogram stationary spectrum for a white-noise-driven cortex: evidence for a general anesthetic-induced phase transition. Phys Rev E. 1999;60(6):7299–311.

  23. 23.

    Zetterberg LH. Estimation of parameters for a linear difference equation with application to EEG analysis. Math Biosci. 1969;5(3–4):227–75.

  24. 24.

    Wennberg A, Zetterberg LH. Application of a computer-based model for EEG analysis. Electroencephalogr Clin Neurophysiol. 1971;31(5):457–68.

  25. 25.

    Zetterberg LH. Recent advances in EEG data processing. Electroencephalogr Clin Neurophysiol Suppl. 1978;34:19–36.

  26. 26.

    Liley DTJ, Sinclair NC, Lipping T, Heyse B, Vereecke HEM, Struys MMRF. Propofol and remifentanil differentially modulate frontal electroencephalographic activity. Anesthesiology. 2010;113(2):292–304.

  27. 27.

    Liley DTJ, Leslie K, Sinclair NC, Feckie M. Dissociating the effects of nitrous oxide on brain electrical activity using fixed order time series modeling. Comput Biol Med. 2008;38(10):1121–30.

  28. 28.

    Schack B, Krause W. Dynamic power and coherence analysis of ultra short-term cognitive processes—a methodical study. Brain Topogr. 1995;8(2):127–36.

  29. 29.

    Tseng SY, Chen RC, Chong FC, Kuo TS. Evaluation of parametric methods in EEG signal analysis. Med Eng Phys. 1995;17(1):71–8.

  30. 30.

    Pardey J, Roberts S, Tarassenko L. A review of parametric modelling techniques for EEG analysis. Med Eng Phys. 1996;18(1):2–11.

  31. 31.

    Barrett AB, Murphy M, Bruno MA, Noirhomme Q, Boly M, Laureys S, Seth AK. Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia. PLoS One. 2012;7(1):e29072.

  32. 32.

    Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet. 2000;355(9205):707–11.

  33. 33.

    Broersen PMT. Automatic spectral analysis with time series models. IEEE Trans Instrum Meas. 2002;51(2):211–6.

  34. 34.

    Sahinovic MD, Eleveld DJ, Heeremans EH, Neckebroek MM, Liley DTJ, Seshagiri CV, Absalom AR, Vereecke HEM, Struys MMRF. Accuracy of the Composite Variability Index and Cortical Index as measures of the balance between nociception and antinociception during anesthesia. Anesth Analg. 2014;119(2):288–301.

  35. 35.

    Cousineau D. Confidence intervals in within-subject designs: a simpler solution to Loftus and Masson’s method. Tutor Quant Methods Psychol. 2005;1(1):42–5.

  36. 36.

    Morey RD. Confidence intervals from normalized data: a correction to Cousineau (2005). Tutor Quant Methods Psychol. 2008;4(2):61–4.

  37. 37.

    Kadel RP, Kip KE. A SAS macro to compute effect size (Cohen’s d) and its confidence interval from raw survey data. In: SouthEast SAS Users Group Conference, Durham, NC, October 14–16 2012.

  38. 38.

    Shafer SL, Varvel JR, Aziz N, Scott JC. Pharmacokinetics of fentanyl administered by computer-controlled infusion pump. Anesthesiology. 1990;73(6):1091–102.

  39. 39.

    Gelberg J, Jonmarker C, Stenqvist O, Werner O. Intravenous boluses of fentanyl, 1 µg kg−1, and remifentanil, 0.5 µg kg−1, give similar maximum ventilatory depression in awake volunteers. Br J Anaesth. 2012;108(6):1028–34.

  40. 40.

    Chi OZ, Sommer W, Jasaitis D. Power spectral analysis of EEG during sufentanil infusion in humans. Can J Anesth. 1991;38(3):275–80.

  41. 41.

    Bazaral MG, Wagner R, Abi-Nader E, Estafanous FG. Comparison of the effects of 15 and 60 [mu]g/kg Fentanyl used for induction of anesthesia in patients with coronary artery disease. Anesth Analg. 1985;64(3):312–8.

  42. 42.

    Kovac AL. Controlling the hemodynamic response to laryngoscopy and endotracheal intubation. J Clin Anesth. 1996;8:63–79.

  43. 43.

    Iyer V, Russell WJ. Induction using fentanyl to suppress the intubation response in the cardiac patient: what is the optimal dose? Anaesth Intensive Care. 1988;16(4):411–7.

  44. 44.

    Martin DE, Rosenberg H, Aukburg SJ, Bartkowski RR, Edwards MW Jr, Greenhow DE, Klineberg PL. Low-dose fentanyl blunts circulatory responses to tracheal intubation. Anesth Analg. 1982;61(8):680–4.

Download references


We acknowledge the assistance of Ms Simone Said (research nurse) during the trial.

Author information

Correspondence to Mehrnaz Shoushtarian.

Ethics declarations

Conflict of interest

This study was supported by funding from Cortical Dynamics Ltd. Mehrnaz Shoushtarian, Louis Delacretaz and David Liley are employed by Cortical Dynamics Ltd., North Perth, WA, Australia.

Ethical standards

The experiments conducted in this trial comply with current laws governing conduct of clinical trials in Australia.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

Calculation of CCS and CI from Linearised Liley Model. (PDF 262 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shoushtarian, M., McGlade, D.P., Delacretaz, L.J. et al. Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl. J Clin Monit Comput 30, 833–844 (2016). https://doi.org/10.1007/s10877-015-9780-x

Download citation


  • Depth of anaesthesia
  • BAR monitor
  • Hypnosis
  • Analgesia