Effects of varying remifentanil concentrations on Analgesia Nociception Index® under propofol: an observational study


Analgesia Nociception Index monitor provides a measurement of the nociception and anti-nociception balance based on heart-rate variability. The aim was to assess the ability of Analgesia Nociception Index (ANI) to detect standard noxious stimulation during anesthesia at different opioid concentrations in comparison to hemodynamic and Bispectral Index parameters. Sixteen patients undergoing general anesthesia with propofol and remifentanil. Standardized tetanic electrical stimulation was applied without any other concurrent stimuli, while different effect site concentrations of remifentanil were increased step-by-step (0.5, 1.5, 3.0, 5 and 7 ng/ml). For each tetanic stimulus, values of the different variables 60 s before and 120 s following the stimulus were analyzed. ANI values decreased significantly 120 s after the stimulus when compared to the mean ANI 60 s before the stimulus (P < 0.01). At lower remifentanil concentrations (0.5 ng/ml), all variables except electromyogram from the Bispectral Index significantly changed after the stimulus but in the higher concentrations (5.0 and 7.0 ng/ml) there was not a significant change. The other variables did not change significantly after the noxious stimulation. ANI was the only variable that positively correlated with the different remifentanil concentrations (R = 0.959, P = 0.01). Our study showed that there was a significant decrease in Analgesia Nociception Index after a tetanic stimulation while hemodynamic and BIS parameters did not change, suggesting that the Analgesia Nociception Index may perform better than traditional hemodynamic parameters at reflecting noxious stimulation. Analgesia Nociception Index significantly changed at lower, but not at higher, remifentanil concentrations.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Evans JM. Pain and awareness during general anaesthesia. Lancet. 1987;2:1033.

    CAS  Article  Google Scholar 

  2. 2.

    Gruenewald M, Ilies C. Monitoring the nociception-anti-nociception balance. Best Pract Res Clin Anaesthesiol. 2013;27:235–47.

    Article  Google Scholar 

  3. 3.

    Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014;112:991–1004.

    CAS  Article  Google Scholar 

  4. 4.

    Logier R, Jeanne M, De Jonckheere J, Dassonneville A, Delecroix M, Tavernier B. PhysioDoloris: a monitoring device for analgesia/nociception balance evaluation using heart rate variability analysis. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:1194–7.

    CAS  Google Scholar 

  5. 5.

    Migeon A, Desgranges FP, Chassard D, Blaise BJ, De Queiroz M, Stewart A, et al. Pupillary reflex dilatation and analgesia nociception index monitoring to assess the effectiveness of regional anesthesia in children anesthetised with sevoflurane. Paediatr Anaesth. 2013;23:1160–5.

    PubMed  Google Scholar 

  6. 6.

    Le Guen M, Jeanne M, Sievert K, Al Moubarik M, Chazot T, Laloe PA, et al. The Analgesia Nociception Index: a pilot study to evaluation of a new pain parameter during labor. Int J Obstet Anesth. 2012;21:146–51.

    Article  Google Scholar 

  7. 7.

    Ledowski T, Tiong WS, Lee C, Wong B, Fiori T, Parker N. Analgesia nociception index: evaluation as a new parameter for acute postoperative pain. Br J Anaesth. 2013;111:627–9.

    CAS  Article  Google Scholar 

  8. 8.

    Ledowski T, Averhoff L, Tiong WS, Lee C. Analgesia Nociception Index (ANI) to predict intraoperative haemodynamic changes: results of a pilot investigation. Acta Anaesthesiol Scand. 2014;58:74–9.

    CAS  Article  Google Scholar 

  9. 9.

    Gruenewald M, Herz J, Schoenherr T, Thee C, Steinfath M, Bein B. Measurement of the nociceptive balance by Analgesia Nociception Index and Surgical Pleth Index during sevoflurane-remifentanil anesthesia. Minerva Anestesiol. 2015;81:480–9.

    CAS  PubMed  Google Scholar 

  10. 10.

    Jeanne M, Delecroix M, De Jonckheere J, Keribedj A, Logier R, Tavernier B. Variations of the analgesia nociception index during propofol anesthesia for total knee replacement. Clin J Pain. 2014;30:1084–8.

    Article  Google Scholar 

  11. 11.

    Gruenewald M, Ilies C, Herz J, Schoenherr T, Fudickar A, Hocker J, et al. Influence of nociceptive stimulation on Analgesia Nociception Index (ANI) during propofol-remifentanil anaesthesia. Br J Anaesth. 2013;110:1024–30.

    CAS  Article  Google Scholar 

  12. 12.

    Funcke S, Sauerlaender S, Pinnschmidt HO, Saugel B, Bremer K, Reuter DA, et al. Validation of Innovative techniques for monitoring nociception during general anesthesia: a clinical study using tetanic and intracutaneous electrical stimulation. Anesthesiology. 2017;127:272–83.

    Article  Google Scholar 

  13. 13.

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

    CAS  Article  Google Scholar 

  14. 14.

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

    CAS  Article  Google Scholar 

  15. 15.

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

    CAS  Article  Google Scholar 

  16. 16.

    Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997;86:10–23.

    CAS  Article  Google Scholar 

  17. 17.

    Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.

    Article  Google Scholar 

  18. 18.

    Jeanne M, Clement C, De Jonckheere J, Logier R, Tavernier B. Variations of the analgesia nociception index during general anaesthesia for laparoscopic abdominal surgery. J Clin Monit Comput. 2012;26:289–94.

    CAS  Article  Google Scholar 

  19. 19.

    Upton HD, Ludbrook GL, Wing A, Sleigh JW. Intraoperative "analgesia nociception index"-guided fentanyl administration during sevoflurane anesthesia in lumbar discectomy and laminectomy: a randomized clinical trial. Anesth Analg. 2017;125:81–90.

    CAS  Article  Google Scholar 

  20. 20.

    Daccache G, Caspersen E, Pegoix M, Monthe-Sagan K, Berger L, Fletcher D, et al. A targeted remifentanil administration protocol based on the analgesia nociception index during vascular surgery. Anaesth Crit Care Pain Med. 2017;36:229–32.

    Article  Google Scholar 

  21. 21.

    Dundar N, Kus A, Gurkan Y, Toker K, Solak M. Analgesia nociception index (ani) monitoring in patients with thoracic paravertebral block: a randomized controlled study. J Clin Monit Comput. 2018;32:481–6.

    Article  Google Scholar 

Download references


The authors would like to thank MDoloris Medical Systems© (Lille, France) for providing the Analgesia Nociception Index (ANI)® monitor and electrodes.


The authors declare no financial support.

Author information



Corresponding author

Correspondence to Sérgio Vide.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Susano, M.J., Vide, S., Ferreira, A.D. et al. Effects of varying remifentanil concentrations on Analgesia Nociception Index® under propofol: an observational study. J Clin Monit Comput 35, 199–205 (2021). https://doi.org/10.1007/s10877-020-00457-3

Download citation


  • Nociception monitoring
  • ANI
  • Analgesia Nociception Index
  • Heart rate variability
  • General anesthesia
  • Target controlled infusion
  • Remifentanil