Skip to main content
SpringerLink
Log in

Impact of intravenous phenylephrine bolus administration on the nociceptive level index (NOL)

Journal of Clinical Monitoring and Computing volume 34, pages 1079–1086 (2020)Cite this article

Abstract

Recently, the nociceptive level index (NOL) was shown to more specifically and sensitively detect noxious stimuli during anesthesia, in comparison to previous methods that relied on such parameters as heart rate (HR) and mean blood pressure (MAP). An ongoing study (NCT#03410485) evaluates the intraoperative combination of both NOL and bispectral (BIS) indices to improve quality of recovery after colorectal surgery. Our ethical committee (REB approval #CER15083) initially agreed on an interim analysis of the data from the first 30 patients. More specifically, this present report analyzed all the intravenous phenylephrine (PE) boluses administered during anesthesia as part of our study protocol to see whether they had a significant impact on NOL values as well as other parameters: HR, MAP, BIS index. For this trial, remifentanil and phenylephrine were given in both groups based on a specific algorithm. All study parameters were recorded electronically. Our analysis for the present specific outcome evaluated NOL index for 30 s before the intravenous PE bolus (1 µg kg−1) was given and until 5 min afterwards. The average NOL values after PE bolus, as well as MAP, HR and BIS indices, were recorded and analyzed. A total of 178 events of PE boluses were identified for 28 patients (two were excluded). Median baseline NOL was 3 (1.8–8.3) CI 95% 5.7–8.7; post-PE bolus: 5.3 (2.7–9.9) (95% CI 6.6–8.9; Wilcoxon matched-pairs signed rank test (WMPSRT), P = 0.0003). When analyzing delta NOL (difference between pre- and post-PE bolus in NOL values) for each patient, the median delta NOL was 2.9 (1.2–6.1) (95% CI 3.6–5.5) with 95% of the subjects keeping a delta NOL under 10. MAP and HR values showed expected significant variations after PE bolus: a slight increase and slight decrease, respectively. BIS index values did not change after PE bolus. Our present results demonstrate that intravenous phenylephrine boluses of 1 µg kg−1 had the expected impact on hemodynamic parameters: a significant but very slight increase in MAP and decrease in HR, which might lack clinical relevance. Our report also demonstrates that these same phenylephrine boluses induce a statistically significant increase of the NOL index which does not seem to have much of a clinical relevance for the novel NOL index used to monitor intraoperative nociception as well as for the more classical BIS index for depth of anesthesia. Nevertheless, doses of intravenous PE bolus used in the present study (1 µg kg−1) might be regarded as smaller than more conventional ones (100–200 µg per bolus). Further studies need to be done with the latter doses.

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

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

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

    Article  Google Scholar 

  2. Latson TW, O’Flaherty D. Effects of surgical stimulation on autonomic reflex function: assessment by changes in heart rate variability. Br J Anaesth. 1993;70:301–5.

    Article  CAS  Google Scholar 

  3. Pichot V, Gaspoz JM, Molliex S, Antoniadis A, Busso T, Roche F, Costes F, Quintin L, Lacour JR, Barthelemy JC. Wavelet transform to quantify heart rate variability and to assess its instantaneous changes. J Appl Physiol. 1999;86:1081–91.

    Article  CAS  Google Scholar 

  4. Jeanne M, Clement C, De Konckheere 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.

    Article  CAS  Google Scholar 

  5. Jeanne M, Logier R, De Konckheere J, Tavernier B. Validation of a graphic measurement of heart rate variability to assess analgesia/nociception balance during general anesthesia. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:1840–3.

    CAS  PubMed  Google Scholar 

  6. Jeanne M, Logier R, De Konckheere J, Tavernier B. Heart rate variability during total intravenous anesthesia: effects of nociception and analgesia. Auton Neurosci. 2009;147:91–6.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  8. Edry R, Recea V, Dikust Y, Sessler DI. Preliminary intraoperative validation of the nociception level index: a noninvasive nociception monitor. Anesthesiology. 2016;125:193–203.

    Article  Google Scholar 

  9. Martini CH, Boon M, Broens SJ, Hekkelman EF, Oudhoff LA, Buddeke AW, Dahan A. Ability of the nociception level, a multiparameter composite of autonomic signals, to detect noxious stimuli during propofol-remifentanil anesthesia. Anesthesiology. 2015;123:524–34.

    Article  CAS  Google Scholar 

  10. Stockle PA, Julien M, Issa R, Decary E, Brulotte V, Drolet P, Henri M, Poirier M, Latulippe JF, Dorais M, Verdonck O, Fortier LP, Richebe P. Validation of the PMD100 and its NOL Index to detect nociception at different infusion regimen of remifentanil in patients under general anesthesia. Minerva Anestesiol. 2018;84:1160–8.

    Article  Google Scholar 

  11. Renaud-Roy E, Stockle PA, Maximos S, Brulotte V, Sideris L, Dube P, Drolet P, Tanoubi I, Issa R, Verdonck O, Fortier LP, Richebe P. Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli. Can J Anaesth. 2019;66:1049–61.

    Article  Google Scholar 

  12. Thiele RH, Nemergut EC, Lynch C. The clinical implications of isolated alpha(1) adrenergic stimulation. Anesth Analg. 2011;113:297–304.

    Article  CAS  Google Scholar 

  13. Thiele RH, Nemergut EC, Lynch C. The physiologic implications of isolated alpha(1) adrenergic stimulation. Anesth Analg. 2011;113:284–96.

    Article  CAS  Google Scholar 

  14. Ngan Kee WD, Lee SW, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015;122:736–45.

    Article  CAS  Google Scholar 

  15. Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg. 2010;111:1230–7.

    Article  CAS  Google Scholar 

  16. Dyer RA, Piercy JL, Reed AR, Lombard CJ, Schoeman LK, James MF. Hemodynamic changes associated with spinal anesthesia for cesarean delivery in severe preeclampsia. Anesthesiology. 2008;108:802–11.

    Article  CAS  Google Scholar 

  17. Rebet O, Andremont O, Gerard JL, Fellahi JL, Hanouz JL, Fischer MO. Preload dependency determines the effects of phenylephrine on cardiac output in anaesthetised patients: a prospective observational study. Eur J Anaesthesiol. 2016;33:638–44.

    Article  CAS  Google Scholar 

  18. Ngan Kee WD, Khaw KS. Vasopressors in obstetrics: what should we be using? Curr Opin Anaesthesiol. 2006;19:238–43.

    Article  Google Scholar 

  19. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. J Pharmacol Pharmacother. 2010;1:100–7.

    Article  Google Scholar 

  20. Krenitsky J. Adjusted body weight, pro: evidence to support the use of adjusted body weight in calculating calorie requirements. Nutr Clin Pract. 2005;20:468–73.

    Article  Google Scholar 

  21. Cardenas-Garcia J, Schaub KF, Belchinov YG, Narasimhan M, Koenig SJ, Mayo PH. Safety of peripheral intravenous administration of vasoactive medication. J Hosp Med. 2015;10:581–5.

    Article  Google Scholar 

  22. Delgado T, Wolfe B, Davis G, Ansari S. Safety of peripheral administration of phenylephrine in a neurologic intensive care unit: a pilot study. J Crit Care. 2016;34:107–10.

    Article  CAS  Google Scholar 

  23. Ngan Kee WD. A random-allocation graded dose-response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology. 2017;127:934–41.

    Article  CAS  Google Scholar 

  24. Futier E, Lefrant JY, Guinot PG, Godet T, Lome E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S, INPRESS Study Group. Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery: a randomized clinical trial. JAMA. 2017;318:1346–57.

    Article  Google Scholar 

  25. Khanna AK, Maheshwari K, Mao G, Liu L, Perez-Protto SE, Chodavarapu P, Schacham YN, Sessler DI. Association between mean arterial pressure and acute kidney injury and a composite of myocardial injury and mortality in postoperative critically III patients: a retrospective cohort analysis. Crit Care Med. 2019;47:910–7.

    Article  CAS  Google Scholar 

  26. Sessler DI, Bloomstone JA, Aronson S, Berry C, Gan TJ, Kellum JA, Plumb J, Mythen MG, Grocott MPW, Edwards MR, Miller TE, Perioperative Quality Initiative-3 Workgroup. Perioperative quality initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery. Br J Anaesth. 2019;122:563–74.

    Article  Google Scholar 

  27. Turan A, Chang C, Cohen B, Saasouh W, Essber H, Yang D, Ma C, Hovepyan K, Khanna AK, Vitale J, Shah A, Ruetzler K, Maheshwari K, Sessler DI. Incidence, severity, and detection of blood pressure perturbations after abdominal surgery: a prospective blinded observational study. Anesthesiology. 2019;130:550–9.

    Article  Google Scholar 

Download references

Acknowledgements

Thanks to Nadia Godin, RN and Research Coordinator and Moulay Idrissi, BEng, MSc for their help at research organization.

Funding

The CINAAMON trial received a grant from the CARF (Canadian Anesthesia Research Foundation) and from Medasense Biometrics Ltd. (independent investigator-initiated trial grant). This study was also supported by the department of anesthesiology and pain medicine of Maisonneuve-Rosemont Hospital, CIUSSS de l’Est de Montreal, University of Montreal.

Author information

Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, University of Montreal, Maisonneuve-Rosemont Hospital, CEMTL, 5415 Boulevard de l’Assomption, Montréal, QC, H1T 2M4, Canada

    Julien Raft, Issam Tanoubi, Olivier Verdonck, Louis-Philippe Fortier, Fabien Espitalier & Philippe Richebe

  2. Department of Anesthesiology, Alexis Vautrin Cancer Institute of Lorraine, University of Lorraine, 6, avenue de Bourgogne, 54511, Vandoeuvre-les-Nancy, France

    Julien Raft

  3. Department of Anesthesiology and Pain Medicine, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, QC, H3T 1J4, Canada

    Marie-Andrée Coulombe & Etienne Renaud-Roy

Authors
  1. Julien Raft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie-Andrée Coulombe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Etienne Renaud-Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Issam Tanoubi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Olivier Verdonck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Louis-Philippe Fortier
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fabien Espitalier
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Philippe Richebe
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study design: JR, MAC, ERR, IT, OV, LPF, FE, PR. Recording data: ERR, OV, LPF, PR. Interpreting data: JR, MAC, ERR, IT, OV, LPF, FE, PR. Data analysis: JR, MAC, PR. Writing manuscript: JR, MAC, PR. Reading and reviewing manuscript: JR, MAC, ERR, IT, OV, LPF, FE, PR.

Corresponding author

Correspondence to Philippe Richebe.

Ethics declarations

Conflict of interest

J.R., M-A.C., E.R-R., I.T., O.V., L-P.F., F.E. declare no conflict of interest. P.R. received honorarium as a consultant for the following companies: Medasense, Abbvie, Medtronic-Covidien, Biosyent, Merck. He has been a member of the Scientific Advisory Board of Medasense Ltd. since 2014.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raft, J., Coulombe, MA., Renaud-Roy, E. et al. Impact of intravenous phenylephrine bolus administration on the nociceptive level index (NOL). J Clin Monit Comput 34, 1079–1086 (2020). https://doi.org/10.1007/s10877-019-00393-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10877-019-00393-x

Keywords

search

Navigation