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Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli

  • Etienne Renaud-Roy
  • Pierre-André Stöckle
  • Sarah Maximos
  • Véronique Brulotte
  • Lucas Sideris
  • Pierre Dubé
  • Pierre Drolet
  • Issam Tanoubi
  • Rami Issa
  • Olivier Verdonck
  • Louis-Philippe Fortier
  • Philippe RichebéEmail author
Reports of Original Investigations

Abstract

Background

The Pain Monitoring Device (PMD) monitor (Medasense Biometrics Ltd., Ramat Gan, Israel) uses the Nociception Level (NOL) index, a multiple parameter-derived index that has recently shown a good sensitivity and specificity to detect noxious stimuli. The aim of this study was to assess the latest version of the device (PMD200TM) on variations of the NOL response after standardized tetanic stimuli to study the correlation between remifentanil doses and NOL.

Methods

Data from 26 patients undergoing midline laparotomy and receiving a desflurane-remifentanil-based anesthetic coupled with low thoracic epidural analgesia were analyzed. A standardized tetanic stimulus was applied to the forearm of the patients at different remifentanil infusion rates. The primary aim was to evaluate the correlation between post-tetanic stimulation NOL values from the PMD200 and remifentanil doses. The NOL index variations after experimental and clinical stimuli were also compared with heart rate (HR), mean arterial pressure (MAP), and Bispectral Index™ (BIS).

Results

A correlation between post-tetanic stimulation NOL values and remifentanil doses was found (r = −0.56; 95% confidence interval [CI], −0.70 to −0.44; P < 0.001). The NOL discriminated noxious from non-noxious states with the maximal Youden’s index value of the NOL receiver operating characteristic (ROC) curve showing a specificity of 88% (95% CI, 69.0 to 100) and sensitivity of 79.1% (95% CI, 56.2 to 95.5). The area under the NOL ROC curve (AUC, 0.9; 95% CI, 0.84 to 0.95) was significantly different from the other variables (P < 0.001 vs HR; P < 0.001 vs MAP; P < 0.001 vs BIS).

Conclusions

The NOL value after noxious stimulus decreased with incremental remifentanil doses, showing a significant inverse correlation between the NOL index and opioid doses. The sensitivity and specificity of NOL to discriminate between noxious and non-noxious stimuli suggests its interesting potential as a monitor of nociception intensity during anesthesia.

Trial registration

www.clinicaltrials.gov (NCT 02884778); 27 July, 2016.

Corrélation entre des doses croissantes de rémifentanil et la réponse de l’indice de nociception NOL après des stimuli peropératoires douloureux

Résumé

Contexte

Le moniteur de la douleur PMD (Pain Monitoring Device) (Medasense Biometrics Ltd., Ramat Gan, Israël) se fonde sur l’indice NOL (Nociception Level), un indice dérivé de paramètres multiples dont la sensibilité et la spécificité se sont avérées élevées pour détecter les stimuli douloureux. L’objectif de cette étude était d’évaluer la dernière version du dispositif (PMD200TM) sur des variations de la réponse NOL après des stimuli tétaniques normalisés afin d’étudier la corrélation entre des doses des rémifentanil et le NOL.

Méthode

Les données de 26 patients subissant une laparotomie médiane et recevant une anesthésie de desflurane-rémifentanil ainsi qu’une analgésie par péridurale thoracique basse ont été analysées. Un stimulus tétanique normalisé a été appliqué à l’avant-bras des patients recevant des perfusions de rémifentanil à différentes doses. L’objectif principal était d’évaluer la corrélation entre les valeurs de NOL après la stimulation tétanique relevées par le PMD200 et les doses de rémifentanil. Les variations de l’indice NOL après les stimuli expérimentaux et cliniques ont également été comparées à la fréquence cardiaque (FC), à la tension artérielle moyenne (TAM), et à l’indice bispectralTM (BIS).

Résultats

Une corrélation a été observée entre les valeurs NOL post stimulation tétanique et les doses de rémifentanil (r = −0,56; intervalle de confiance [IC] 95 %, −0,70 à −0,44; P < 0,001). Le NOL a distingué les états nociceptifs des états non nociceptifs, la valeur maximale de l’indice de Youden de la courbe ROC (courbe caractéristique efficace – receiver operating characteristic) montrant une spécificité de 88 % (IC 95 %, 69,0 à 100) et une sensibilité de 79,1 % (IC 95 %, 56,2 à 95,5). La surface sous la courbe ROC de NOL (SSC, 0,9; IC 95 %, 0,84 à 0,95) était significativement différente par rapport aux autres variables (P < 0,001 vs FC; P < 0,001 vs TAM; P < 0,001 vs BIS).

Conclusion

La valeur NOL après un stimulus nociceptif a baissé avec des doses croissantes de rémifentanil, ce qui démontre une corrélation inverse significative entre l’indice NOL et les doses opioïdes. La sensibilité et la spécificité du NOL pour distinguer les stimuli nociceptifs et non nociceptifs suggèrent que cet indice pourrait être intéressant pour monitorer l’intensité de la nociception pendant l’anesthésie.

Enregistrement de l’étude

www.clinicaltrials.gov (NCT 02884778); 27 juillet 2016.

Notes

Acknowledgements

This study was supported by an Independent Investigator Initiated Trial Research Grant after a contract set by both the parties’ attorneys and between the Research Center of HMR and the company Medasense LTD, Ramat Gan, Israel, and by the Department of Anesthesiology of Maisonneuve-Rosemont Hospital. Nadia Godin was the research nurse and coordinator for this study.

Conflict of interest

Dr. Philippe Richebé is a member of the advisory board of the company Medasense and is a consultant for this company; as such, he perceived honorarium from 2015 until present.

Editorial responsibility

This submission was handled by Dr. Hilary P. Grocott, Editor-in-Chief, Canadian Journal of Anesthesia.

Author contributions

Etienne Renaud-Roy, Veronique Brulotte, Issam Tanoubi, Olivier Verdonck, and Louis-Philippe Fortier contributed to the design, execution, analysis, and revision. Pierre-Andre Stöckle contributed to the analysis, writing, and revision. Sarah Maximos contributed to the execution, analysis, and revision. Lucas Sideris and Pierre Dubé contributed to the design, execution, and revision. Pierre Drolet contributed to the design, analysis, writing, and revision. Rami Issa contributed to the execution and revision. Philippe Richebé is the principal investigator of the study and contributed to the design, execution, analysis, interpretation, drafting, writing, and revision of the article.

Supplementary material

12630_2019_1372_MOESM1_ESM.pdf (97 kb)
Supplementary material 1 (PDF 97 kb)

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Copyright information

© Canadian Anesthesiologists' Society 2019

Authors and Affiliations

  • Etienne Renaud-Roy
    • 1
  • Pierre-André Stöckle
    • 1
  • Sarah Maximos
    • 1
  • Véronique Brulotte
    • 1
  • Lucas Sideris
    • 2
  • Pierre Dubé
    • 2
  • Pierre Drolet
    • 1
  • Issam Tanoubi
    • 1
  • Rami Issa
    • 1
  • Olivier Verdonck
    • 1
  • Louis-Philippe Fortier
    • 1
  • Philippe Richebé
    • 1
    Email author
  1. 1.Department of Anesthesiology of Maisonneuve-Rosemont Hospital, CIUSSS de l’Est de l’Ile de MontrealUniversity of MontrealMontrealCanada
  2. 2.Department of Surgery, Maisonneuve-Rosemont Hospital, CIUSSS de l’Est de l’Ile de MontrealUniversity of MontrealMontrealCanada

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