{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T03:31:55Z","timestamp":1769571115593,"version":"3.49.0"},"reference-count":21,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Quantifying intraoperative nociceptive responses under general anesthesia remains challenging, particularly during complex procedures such as spinal surgery. The Nociception Level (NoL) index is a multiparametric tool designed to reflect the dynamic balance between nociception and analgesia in anesthetized patients. This study aimed to evaluate NoL fluctuations during predefined phases of spinal surgery and assess their relationship to anesthetic administration. Methods: This prospective observational study enrolled 44 adult patients undergoing lumbar discectomy, laminectomy, or spinal fusion under remifentanil\u2013propofol anesthesia. Continuous NoL monitoring was performed using the PMD100\u2122 system. Sixteen anatomically and procedurally defined surgical phases were analyzed. The primary outcome was the mean NoL value in each phase. The secondary outcome was the association between NoL values and intraoperative infusion rates of remifentanil and propofol. Repeated-measures ANOVA with Bonferroni correction was used for phase comparisons. Results: Mean NoL values remained within the target range (10\u201325) in most phases. However, significant elevations were observed during pedicle screw insertion (mean 27.9, SD \u00b1 17.7), cage insertion (27.6, SD \u00b1 10.5), and flavectomy (28.0, SD \u00b1 27.0), indicating increased nociceptive burden. The lowest NoL values occurred during skin closure (16.6, SD \u00b1 11.2) and discectomy (18.0, SD \u00b1 2.8). Propofol and remifentanil infusion rates remained within standard clinical ranges but were slightly elevated during high-NoL phases. Conclusions: Despite standardized anesthesia, distinct nociceptive peaks were observed during specific stages of spinal surgery. These findings suggest that NoL monitoring may help identify high-nociception phases and guide tailored analgesic strategies. Future randomized trials are warranted to assess whether protocolized NoL-guided anesthesia improves intraoperative management and postoperative outcomes.<\/jats:p>","DOI":"10.3390\/jcm14248960","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:32:03Z","timestamp":1766068323000},"page":"8960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intraoperative Nociception Monitoring Using the NoL Index: Phase-Specific Assessment of Nociceptive Responses During Spinal Surgery"],"prefix":"10.3390","volume":"14","author":[{"given":"Amran","family":"Khalaila","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8724-129X","authenticated-orcid":false,"given":"Mahmod","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Carmel Hospital, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6466-6420","authenticated-orcid":false,"given":"Yaron","family":"Berkovich","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Carmel Hospital, Haifa 3436212, Israel"},{"name":"Faculty of Medicine, Technion Institute of Technology, Haifa 3200003, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Sleiman","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Carmel Hospital, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1491-5837","authenticated-orcid":false,"given":"Eitan","family":"Mangoubi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Grach","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umar","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adva","family":"Gutman Tirosh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Shpigelman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arsen","family":"Shpigelman","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Carmel Hospital, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1177\/0269216308095701","article-title":"Pain assessment tools in palliative care: An urgent need for consensus","volume":"22","author":"Hjermstad","year":"2008","journal-title":"Palliat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1097\/AJP.0000000000000083","article-title":"Variations of the analgesia nociception index during propofol anesthesia for total knee replacement","volume":"30","author":"Jeanne","year":"2014","journal-title":"Clin. J. Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1515\/sjpain-2018-0012","article-title":"The validity of pain intensity measures: What do the NRS, VAS, VRS, and FPS-R measure?","volume":"18","author":"Thong","year":"2018","journal-title":"Scand. J. Pain"},{"key":"ref_4","unstructured":"Barash, P.G., Cullen, B.F., Stoelting, R.K., Cahalan, M.K., Stock, M.C., Ortega, R., Sharar, S.R., and Holt, N.F. (2017). Clinical Anesthesia, Lippincott Williams & Wilkins (LWW). [8th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10877-013-9487-9","article-title":"Monitoring the nociception level: A multi-parameter approach","volume":"27","author":"Kliger","year":"2013","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/ALN.0000000000000757","article-title":"Ability of the nociception level, a multiparameter composite of autonomic signals, to detect noxious stimuli during propofol\u2013remifentanil anesthesia","volume":"123","author":"Martini","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/ALN.0000000000001130","article-title":"Preliminary intraoperative validation of the nociception level index: A noninvasive nociception monitor","volume":"125","author":"Edry","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.bja.2020.07.057","article-title":"Reduced postoperative pain using Nociception Level-guided fentanyl dosing during sevoflurane anaesthesia: A randomized controlled trial","volume":"125","author":"Meijer","year":"2020","journal-title":"Br. J. Anaesth."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1097\/ALN.0000000000002634","article-title":"Nociception-Guided Versus Standard Care During Remifentanil\u2014Propofol Anesthesia: A Randomized Controlled Trial","volume":"130","author":"Meijer","year":"2019","journal-title":"Anesthesiology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"van der Wal, I., Meijer, F., Fuica, R., Silman, Z., Boon, M., Martini, C., van Velzen, M., Dahan, A., Niesters, M., and Gozal, Y. (2023). Intraoperative use of the machine learning-derived nociception level monitor results in less pain in the first 90 min after surgery. Front. Pain Res., 3.","DOI":"10.3389\/fpain.2022.1086862"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/bja\/aet110","article-title":"Prospective observational study of the non-invasive assessment of immediate postoperative pain using the analgesia\/nociception index (ANI)","volume":"111","author":"Boselli","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1093\/bja\/aet111","article-title":"Analgesia nociception index: Evaluation as a new parameter for acute postoperative pain","volume":"111","author":"Ledowski","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s10877-019-00399-5","article-title":"Evaluation of Surgical Pleth Index and Analgesia Nociception Index as surrogate pain measures in conscious postoperative patients: An observational study","volume":"34","author":"Lee","year":"2020","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.23736\/S0375-9393.18.12837-9","article-title":"Analgesia Nociception Index-guided intraoperative fentanyl consumption and postoperative analgesia in patients receiving scalp block versus incision-site infiltration for craniotomy","volume":"84","author":"Theerth","year":"2018","journal-title":"Minerva Anestesiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1038\/s41598-022-06993-z","article-title":"Comparison between Analgesia Nociception Index (ANI) and self-reported measures for diagnosing pain in conscious individuals: A systematic review and meta-analysis","volume":"12","author":"Baroni","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/bja\/aev361","article-title":"Postoperative pain assessment in children: A pilot study of the usefulness of the analgesia nociception index","volume":"115","author":"Gall","year":"2015","journal-title":"Br. J. Anaesth."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1109\/TBME.2007.896584","article-title":"A novel fuzzy pain demand index derived from patient-controlled analgesia for postoperative pain","volume":"54","author":"Shieh","year":"2007","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Saunders, R., and Weissbrod, R. (2020, January 18\u201320). Cost Benefit of Personalizing Intraoperative Pain Management. Proceedings of the ISPOR Virtual Conference, Virtual.","DOI":"10.1016\/j.jval.2020.04.1220"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bja.2018.09.031","article-title":"Assessing pain in the postoperative period: Analgesia Nociception Index (TM) versus pupillometry","volume":"123","author":"Charier","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ijoa.2012.01.001","article-title":"The Analgesia Nociception Index: A pilot study to evaluation of a new pain parameter during labor","volume":"21","author":"Jeanne","year":"2012","journal-title":"Int. J. Obstet. Anesth."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nadeau, S.E., Wu, J.K., and Lawhern, R.A. (2021). Opioids and Chronic Pain: An Analytic Review of the Clinical Evidence. Front. Pain Res., 2.","DOI":"10.3389\/fpain.2021.721357"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/24\/8960\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T03:25:29Z","timestamp":1766719529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/24\/8960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":21,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["jcm14248960"],"URL":"https:\/\/doi.org\/10.3390\/jcm14248960","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]}}}