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October 23, 2016
10/23/2016 10:00:00 AM - 10/23/2016 12:00:00 PM
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Quantified Analgesic Effect of Intraoperative 50% N2O Inhalation by the NoL and ANI Nociception Indices
Philippe G. Richebe, M.D.,Ph.D., Elizabeth Decary, M.D., Rami Issa, M.D., Sarah Maximos, M.S., Louis-Philippe Fortier, M.D.,Ph.D., Olivier Verdonck, M.D., M.S.
University of Montreal, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
Disclosures:  P.G. Richebe: None. E. Decary: None. R. Issa: None. S. Maximos: None. L. Fortier: None. O. Verdonck: None.
Introduction: For decades, nitrous oxide (N2O) was used during general anesthesia (GA) to decrease the anesthetic consumption and as an analgesic agent. To date, the monitoring of intraoperative pain was mostly based on mean blood pressure (MBP) and heart rate (HR). Medasense Biometrics Ltd (Tel-Aviv, Israel) developed a multi-parameter index: NoL, which incorporates HR, HR Variability (HRV), plethysmograph wave amplitude, skin conductance level and fluctuations, and their time derivatives. The NoL Index obtained on the Medasense PMD200™ device goes from 0 to 100, with a lower score for less painful stimulation. Instantaneous Analgesia Nociception Index (iANI) is based on a single parameter: HRV. iANI varies from 100 (no pain) to 0 (high pain).

Objective: to observe the variations of intraoperative pain indices NoL and iANI following standardized forearm electrical stimulus at 0% vs 50% ET-N2O.


Prospective, open label, observational study. NCT02602379. 40 patients will be included. Patients undergo GA for laparotomies with preoperative epidural placement. Epidural was loaded prior to incision. After GA induction and intubation, remifentanil (RF) infusion was decreased from 0.05 to 0.005 mcg/kg/min (very low dose). After 10 minutes at this RF concentration, patient was free of any stimulation. A standardized electrical stimulus (70mA, 100Hz, 30sec) was then applied on the forearm and responses of HR, MBP, iANI, NoL and BIS indices were recorded. The ET-N2O at the time of this first stimulus is 0%. Then ET-N2O was set at 50% and an identical electrical stimulus was applied.

Comparison of medians (Q1;Q3) of peak of HR, MBP, NoL, iANI, and BIS after stimulations at 0 and 50% were done using Wilcoxon Sign-Rank test. Comparison of % variation of each index between 0 and 50% ET-N2O after electrical stimulus was done using McNemar’s test.

Results: we present intermediary analyses of the data of the first 10 patients included. 7 out of the 10 patients had all the necessary data for statistical analysis at this point.

After the stimulus at 0% ET-N2O: a) HR and MBP significantly increased from baseline (p=0.0156 for both parameters) but this increase in HR and MBP went above the classical 20% of increase in only 14% of patients for both criteria; b) NoL index and iANI significantly changed after stimulation at ET-N2O 0% (p=0.0156 for both indices): 86% of patients had a NoL going above the threshold of 15, and 57% of patients had an iANI go below the threshold of 40; c) BIS values did not change significantly after stimulation at 0% ET-N2O.

When ET-N2O was set at 50%, HR and MBP changes after stimulus were not significantly different from the small changes observed at 0% (p=0.156 for HR and p=0.109 for MBP) and HR and BP never went above 20% variation. Delta NoL after stimulus was 10 (4;23) at ET-N2O 50% versus 24 (17;37) at 0% (p=0.0625) and the % variation of the NoL was significantly greater when ET-N2O was at 0% versus 50% (p=0.031). Only 43% of patients had a NoL go above the threshold of 15 (versus 86% at 0% ET-N2O, p=0.26). iANI variation after stimulus was 33 (0;44) at 50% versus 37 (36;58) at 0% (p=0.156). No patient had iANI go below 40 at ET-N2O 50%. BIS values did not change significantly after stimulation at 50%.

Discussion: these preliminary results show that the analgesic effect of N2O set at ET of 50% is best monitored by the NoL variations after standard stimulus. Even if the delta NoL is not significant, the p-value is close to significance and we can expect to reach significance once all the 40 patients are included. Although iANI variations are similar between 0 and 50% ET-N2O, less patients reached values below the threshold of 40 when N2O was high, indirectly suggesting some analgesic effect of N2O. HR and MBP seem to be much less specific and sensitive to detect pain compared to ANI and NoL. In conclusion, we suggest that NoL might be the best parameter to evaluate nociceptive response to a standardized stimulus and to properly quantify the analgesic effect of 50% ET-N2O.

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