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October 13, 2013
8:00:00 AM - 9:30:00 AM
Room Room 123
Validation of the qNOX Pain/Nociception Index for Monitoring Loss of Response to Tetanic Stimulation During General Anaesthesia.
Erik W. Jensen, Ph.D., Pedro L. Gambús, M.D., Jose F. Valencia, Ph.D., Mathieu Jospin, M.Eng., Xavier Borrat, Ph.D., Michel Struys, M.D.,F.R.C.A, Hugo P. Vereecke, Ph.D., Patricia P. Pineda, Student
Technical University of Barcelona, Barcelona, Spain

For the last two decades monitoring of the hypnotic level by EEG has been refined and is now an accepted tool in the OR. The assessment of nociception has proven far more complex. The objective of this study was the validation of a new EEG derived, pain and nociception index, termed qNOX.


This study was based on data previously published1, including 45 adult female patients, who were scheduled to undergo ambulatory gynecological surgery.

Initially, a propofol effect-site concentration of 1.5 ug/ml was targeted in the three groups, while remifentanil was targeted 0, 2 or 4 ng/ml respectively.

The qNOX was developed from EEG matched with clinical signs from sedated or anaesthetised patients. Several frequency ratios were defined and the four with the best prediction probability of response to noxious stimuli were fed into an Adaptive Neuro Funzzy Inference System (ANFIS) Model, where the output was the qNOX.

Two versions of the qNOX are presented, qNOX A where the index was trained on data recorded during endoscopy and while awake 2, and qNOX B where the training set was the one described in the methods using the leave one out method. The qNOX was defined by feeding 4 EEG/EMG frequency bands (5-90 Hz) into an ANFIS model. A combination between qNOX B and predicted effect site concentration of remifentanil was also evaluated. In this case a model for each concentration of remifentanil was calculated. The prediction probability and the standard error Pk(SE) of qNOX A and qNOX B versus loss of response to tetanic stimulation was calculated.


The results of the Pk analysis are shown in table 1.

0.74(0.02) 0.86(0.01) 0.86(0.01) 0.75(0.02)

0.74(0.02) 0.82(0.01) 0.88(0.01) 0.87(0.01)

0.86(0.01) 0.94(0.01) 0.96(0.01) 0.92 (0.01)

Between qNOX A and qNOX B, the qNOX B showed the best performance. Adding the Ce remi to the model increased significantly the Pk value.


The study shows that the EEG is capable of predicting the loss of response to tetanic stimulation during propofol and remifentanil anaesthesia.

It was expected that qNOX B would give the best performance since the training and validation data were from the same protocol. Adding the concentration of Ce remi, which would be possible if the infusion pumps and the EEG monitor was an integrated device, should be studied further.

The qNOX and a previously published drug interaction model (NSRI) 3 performed equally well in this dataset (pK=0.87) whereas the combination of the qNOX and the remifentanil effect site concentration had a significantly higher pk =0.92.


1 Struys MM, Vereecke H, Moerman A, Jensen EW, Verhaeghen D, De Neve N, Dumortier FJ, Mortier EP. Ability of the bispectral index, autoregressive modelling with exogenous input-derived auditory evoked potentials, and predicted propofol concentrations to measure patient responsiveness during anesthesia with propofol and remifentanil. Anesthesiology. 2003 Oct;99(4):802-12.

2 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 Feb;112(2):331-9.

3 Luginbühl M, Schumacher PM, Vuilleumier P, Vereecke H, Heyse B, Bouillon TW, Struys MM. Noxious stimulation response index. a novel anesthetic state index based on hypnotic-opioid interaction. Anesthesiology. 2010 Apr;112(4):872-80.
Figure 1

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