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


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.

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


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.

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Authors and Affiliations



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.

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Correspondence to Philippe Richebe.

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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.

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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).

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