Comparison of the qCON and qNOX indices for the assessment of unconsciousness level and noxious stimulation response during surgery

Abstract

The objective of this work is to compare the performances of two electroencephalogram based indices for detecting loss of consciousness and loss of response to nociceptive stimulation. Specifically, their behaviour after drug induction and during recovery of consciousness was pointed out. Data was recorded from 140 patients scheduled for general anaesthesia with a combination of propofol and remifentanil. The qCON 2000 monitor (Quantium Medical, Barcelona, Spain) was used to calculate the qCON and qNOX. Loss of response to verbal command and loss of eye-lash reflex were assessed during the transition from awake to anesthetized, defining the state of loss of consciousness. Movement as a response to laryngeal mask (LMA) insertion was interpreted as the response to the nociceptive stimuli. The patients were classified as movers or non-movers. The values of qCON and qNOX were statistically compared. Their fall times and rise times defined at the start and at the end of the surgery were calculated and compared. The results showed that the qCON was able to predict loss of consciousness such as loss of verbal command and eyelash reflex better than qNOX, while the qNOX has a better predictive value for response to noxious stimulation such as LMA insertion. From the analysis of the fall and rise times, it was found that the qNOX fall time (median: 217 s) was significantly longer (p value <0.05) than the qCON fall time (median: 150 s). At the end of the surgery, the qNOX started to increase in median at 45 s before the first annotation related to response to stimuli or recovery of consciousness, while the qCON at 88 s after the first annotation related to response to stimuli or recovery of consciousness (p value <0.05). The indices qCON and qNOX showed different performances in the detection of loss of consciousness and loss of response to stimuli during induction and recovery of consciousness. Furthermore, the qCON showed faster decrease during induction. This behaviour is associated with the hypothesis that the loss of response to stimuli (analgesic effect) might be reached after the loss of consciousness (hypnotic effect). On the contrary, the qNOX showed a faster increase at the end of the surgery, associated with the hypothesis that a higher probability of response to stimuli might be reached before the recovery of consciousness.

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

Fig. 1
Fig. 2

References

  1. 1.

    Lennmarken C, Sandin R. Neuromonitoring for awareness during surgery. Lancet. 2004;363:1747–8.

    Article  PubMed  Google Scholar 

  2. 2.

    Vakkuri A, Yli-Hankala A, Sandin R, Mustola S, Høymork S, Nyblom S, Talja P, Sampson T, van Gils M, Viertiö-Oja H. Spectral entropy monitoring is associated with reduced propofol use and faster emergence in propofol–nitrous oxide–alfentanil anesthesia. Anesthesiology. 2005;103:274–9.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Recart A, White PF, Wang A, Gasanova I, Byerly S, Jones SB. Effect of auditory evoked potential index monitoring on anesthetic drug requirements and recovery profile after laparoscopic surgery: a clinical utility study. Anesthesiology. 2003;99:813–8.

    Article  PubMed  Google Scholar 

  4. 4.

    Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg. 2005;100:4–10.

    Article  PubMed  Google Scholar 

  5. 5.

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

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Mashour GA, Shanks A, Tremper KK, Kheterpal S, Turner CR, Ramachandran SK, Picton P, Schueller C, Morris M, Vandervest JC, Lin N, Avidan MS. Prevention of intraoperative awareness with explicit recall in an unselected surgical population: a randomized comparative effectiveness trial. Anesthesiology. 2012;117(4):717–25.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Migeon A, Desgranges FP, Chassard D, Blaise BJ, De Queiroz M, Stewart A, Cejka JC, Combet S, Rhondali O. Pupillary reflex dilatation and analgesia nociception index monitoring to assess the effectiveness of regional anesthesia in children anesthetised with sevoflurane. Paediatr Anaesth. 2013;23(12):1160–5.

    PubMed  Google Scholar 

  8. 8.

    Jensen EW, Lindholm P, Henneberg SW. Autoregressive modeling with exogenous input of middle-latency auditory-evoked potentials to measure rapid changes in depth of anesthesia. Methods Inf Med. 1996;35(3):256–60.

    CAS  PubMed  Google Scholar 

  9. 9.

    Henneberg SW, Rosenborg D, Jensen EW, Ahn P, Burgdorff B, Thomsen LL. Peroperative depth of anaesthesia may influence postoperative opioid requirements. Acta Anaesthesiol Scand. 2005;49:2293–6.

    Article  Google Scholar 

  10. 10.

    Rehberg B, Ryll C, Hadzidiakos D, Dincklage FW, Baars JH. Variability comparison of the composite auditory evoked potential index and the bispectral index during propofol-fentanyl anesthesia. Technol Comput Simul. 2008;107(1):117–24.

    Google Scholar 

  11. 11.

    Jensen EW, Litvan H, Revuelta M, Rodriguez BE, Caminal P, Martinez P, Vereecke H, Struys MM. Cerebral state index during propofol anesthesia: a comparison with the bispectral index and the A-line ARX index. Anesthesiology. 2006;105:28–36.

    Article  PubMed  Google Scholar 

  12. 12.

    Boselli E, Daniela-Ionescu M, Bégou G, Bouvet L, Dabouz R, Magnin C, Allaouchiche B. Prospective observational study of the non-invasive assessment of immediate postoperative pain using the analgesia/nociception index (ANI). Br J Anaesth. 2013;111(3):453–9.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Storm H. Changes in skin conductance as a tool to monitor nociceptive stimulation and pain. Curr Opin Anaesthesiol. 2008;21(6):796–804.

    Article  PubMed  Google Scholar 

  14. 14.

    Schneider G, Jordan D, Schwarz G, Bischoff P, Kalkman CJ, Kuppe H, Rundshagen I, Omerovic A, Kreuzer M, Stockmanns G, Kochs EF. Monitoring depth of anesthesia utilizing a combination of electroencephalographic and standard measures. Anesthesiology. 2014;120(4):819–28.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Ben-Israel N, Kliger M, Zuckerman G, Katz Y, Edry R. Monitoring the nociception level: a multi-parameter approach. J Clin Monit Comput. 2013;27(6):659–68.

    Article  PubMed  Google Scholar 

  16. 16.

    Barvais L, Engelman E, Eba JM, Coussaert E, Cantraine F, Kenny GN. Effect site concentrations of remifentanil and pupil response to noxious stimulation. Br J Anaesth. 2003;91(3):347–52.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Rollins MD, Feiner JR, Lee JM, Shah S, Larson M. Pupillary effects of high-dose opioid quantified with infrared pupillometry. Anesthesiology. 2014;121(5):1037–44.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Gruenewald M, Ilies C, Herz J, Schoenherr T, Fudickar A, Höcker J, Bein B. Influence of nociceptive stimulation on analgesia nociception index (ANI) during propofol–remifentanil anaesthesia. Br J Anaesth. 2013;110:1024–30.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Luginbuhl M, Schumacher PM, Vuilleumier P, Vereecke H, Heyse B, Bouillon TW, Struys M. Noxious stimulation response index: a novel anesthetic state index based on hypnotic-opioid interaction. Anesthesiology. 2010;112(4):872–80.

    Article  PubMed  Google Scholar 

  20. 20.

    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;100:1353–72.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Vereecke HEM, Hannivoort L N, Proost J H, Eleveld D J, Struys MMRF, Luginbühl M (2014) Predictive performance of the noxious stimulation response index as a measure of anesthetic potency during sevoflurane, propofol and remifentanil anesthesia. International Society for Anaesthetic Pharmacology (ISAP) Annual Meeting 2014. http://f1000research.com/posters/1097048.

  22. 22.

    von Dincklage F, Correll C, Schneider MH, Rehberg B, Baars JH. Utility of nociceptive flexion reflex threshold, bispectral index, composite variability index and noxious stimulation response index as measures for nociception during general anaesthesia. Anaesthesia. 2012;67(8):899–905.

    Article  Google Scholar 

  23. 23.

    Jensen EW, Valencia JF, López A, Anglada T, Agustí M, Ramos Y, Gambus P. Monitoring hypnotic effect and nociception with two EEG-derived indices, qCON and qNOX, during general anaesthesia. Acta Anaesthesiol Scand. 2014;58(8):933–41.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Schnider TW, Minto CF, Shafer SL, Gambus PL, Andresen C, Goodale DB, Youngs EJ. The influence of age on propofol pharmacodynamics. Anesthesiology. 1999;90:1502–16.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, Youngs EJ. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998;88:1170–82.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, Muir KT, Mandema JW, Shafer SL. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil: I model development. Anesthesiology. 1997;86:10–23.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil: II Model application. Anesthesiology. 1997;86:24–33.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Altman DG. Practical statistics for medical research. London: Chapman & Hall; 1991.

    Google Scholar 

  29. 29.

    Smith WD, Dutton RC, Smith NT. Measuring the performance of anesthetic depth indicators. Anesthesiology. 1996;84:38–51.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Irwin MG, Hui TWC, Milne SE, Kenny GNC. Propofol effective concentration 50 and its relationship to bispectral index. Anaesthesia. 2002;57(3):242–8.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Gepts E. Pharmacokinetic concepts for TCI anaesthesia. Anaesthesia. 1998;53:4–12.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Stuart PC, Stott SM, Millar A, Kenny GN, Russell D. Propofol with and without nitrous oxide. Br J Anaesth. 2000;85:666.

    Google Scholar 

  33. 33.

    Wakeling HG, Zimmerman JB, Howell S, Glass PSA. Targeting effect compartment or central compartment concentration of propofol. Anesthesiology. 1999;90:92–7.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Borrat X, Trocóniz IF, Valencia JF, Rivadulla S, Sendino O, Llach J, Castells A. Modeling the Influence of the A118G polymorphism in the OPRM1 gene and of noxious stimulation on the synergistic relation between propofol and remifentanil sedation and analgesia in endoscopic procedures. J Am Soc Anesthesiol. 2013;118(6):1395–407.

    CAS  Article  Google Scholar 

  35. 35.

    Glass PS, Hardman D, Kamiyama Y, Quill TJ, Marton G, Donn KH, Hermann D. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil (GI87084B). Anesth Analg. 1993;77:1031–40.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Egan TD, Lemmens HJ, Fiset P, Hermann DJ, Muir KT, Stanski DR, Shafer SL. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology. 1993;79:881–92.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Glass PS, Gan TJ, Howell S. A review of the pharmacokinetics and pharmacodynamics of remifentanil. Anesth Analg. 1999;89(4S):7.

    Article  Google Scholar 

  38. 38.

    Kissin I. Depth of anaesthesia and bispectral index monitoring. Anesth Analg. 2000;90:1114–7.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Tams C, Johnson K. Prediction variability of combined pharmacokinetic pharmacodynamic models: a simulation study of propofol in combination with remifentanil and fentanyl. J Anesth Clin Res. 2014;5:393.

    Article  Google Scholar 

  40. 40.

    Kapila A, Glass P, Jacobs J, Muir K, Hermann D, Shiraishi M, Smith R. Measured context-sensitive half times of remifentanil and alfentanil. Anesthesiology. 1995;83:968–75.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Zbinden AM, Maggiorini M, Petersen-Felix S, Lauber R, Thomson DA, Minder CE. Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia. I. Motor reactions. Anesthesiology. 1994;80:253–60.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Katoh T, Ikeda K. The effects of fentanyl on sevoflurane requirements for loss of consciousness and skin incision. J Am Soc Anesthesiol. 1998;88(1):18–24.

    CAS  Article  Google Scholar 

  43. 43.

    Gambús PL, Jensen EW, Jospin M, Borrat X, Martínez Pallí G, Fernández-Candil J, Valencia JF, Barba X, Caminal P, Trocóniz IF. Modeling the effect of propofol and remifentanil combinations for sedation-analgesia in endoscopic procedures using an adaptive neuro fuzzy inference system (ANFIS). Anesth Analg. 2011;112(2):331–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The qNOX was based on an idea from the Department of Anesthesia Hospital CLINIC de Barcelona (Spain) funded by grant PS09/01209 of the Fondo de Investigaciones Sanitarias (FIS), Health Department, Government of Spain and has been developed in collaboration with Quantium Medical.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Umberto Melia.

Ethics declarations

Conflicts of interest

Umberto Melia, Erik Weber Jensen, Joan Fontanet, Eva Gabarron and Patricia Pineda are employees of Quantium Medical. Quantium Medical is the commercial developer of both qCON and qNOX indices.

Ethical Statements

The study was performed after IRB approval (Committee on Ethics in Research, Hospital CLINIC de Barcelona no 2013/8356). All the patients has written informed consent.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Melia, U., Gabarron, E., Agustí, M. et al. Comparison of the qCON and qNOX indices for the assessment of unconsciousness level and noxious stimulation response during surgery. J Clin Monit Comput 31, 1273–1281 (2017). https://doi.org/10.1007/s10877-016-9948-z

Download citation

Keywords

  • Anesthesia monitor
  • Nociception
  • Electroencephalography
  • Clinical indices