{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:44:08Z","timestamp":1792176248690,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Achieving profound pulpal anaesthesia in patients with symptomatic irreversible pulpitis (SIP) remains a significant clinical challenge, as standard inferior alveolar nerve blocks (IANB) frequently fail due to localized inflammation. This clinical trial evaluated the effect of preoperative systemic enzyme therapy [trypsin, bromelain, and rutoside (TBR)] on anaesthetic success and postoperative pain in patients with symptomatic irreversible pulpitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      In this randomized, triple\u2010blind, parallel\u2010arm clinical trial, 124 healthy adults with SIP in a single mandibular molar were randomly allocated (1:1:1:1) to four groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931): Group FG (trypsin 100\u2009mg\/bromelain 90\u2009mg\/rutoside 48\u2009mg), Group DF (diclofenac potassium 50\u2009mg), Group PD (prednisolone 20\u2009mg), or Group PB (placebo). One hour after premedication, a standard IANB (1.8\u2009mL 4% articaine, 1:100\u2009000 epinephrine) was administered. The primary outcome was anaesthetic success, defined as the ability to complete endodontic procedures with no or mild pain (NRS \u2264\u20093). Secondary outcomes included postoperative pain intensity (NRS 0\u201310) recorded at 6, 12, 24, 48, 72\u2009h, and 7\u2009days, and rescue analgesic intake.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data of all 124 enrolled patients was analysed. Premedication significantly influenced IANB success (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Group FG (87.1%) and group PD (83.9%) achieved significantly higher success rates than group PB (35.5%); the RR of success for group FG compared to PB was 2.45 (99.17% CI: 1.26, 4.77), and for group PB compared to PD was 0.44 (99.17% CI: 0.22, 0.87). Group FG also showed significantly higher success than group DF RR of success for group DF compared to FG was 0.59 (99.17% CI: 0.36, 0.97). Group FG demonstrated significantly lower postoperative pain scores through 72\u2009h compared to the placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). There were no significant differences in rescue analgesic intake (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.320) or reported adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Premedication with the TBR combination significantly improved the success rate of IANB and reduced postoperative pain in mandibular molars with SIP with clinical efficacy comparable to prednisolone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Implications<\/jats:title>\n                    <jats:p>Systemic enzyme therapy may offer a viable, natural, and potentially safer alternative to corticosteroids or NSAIDs for enhancing pulpal anaesthesia and managing postoperative pain in symptomatic irreversible pulpitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT06298383\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70231","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:30:20Z","timestamp":1784529020000},"page":"2372-2382","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Premedication With Trypsin, Bromelain and Rutoside Combination on Anaesthetic Success and Postoperative Pain in Patients With Symptomatic Irreversible Pulpitis: A Randomized Controlled Trial"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-2224","authenticated-orcid":false,"given":"Maha","family":"Nasr","sequence":"first","affiliation":[{"name":"Department of Endodontics, Faculty of Oral and Dental Medicine Egyptian Russian University  Badr City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2627-343X","authenticated-orcid":false,"given":"Nermine","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Faculty of Dentistry Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13678"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/aej.12249"},{"issue":"12","key":"e_1_2_13_4_1","first-page":"83","article-title":"Effect of Ketorolac Premedication on Anesthetic Efficiency of Inferior Alveolar Nerve Block, Pre\u2010Treatment and Post\u2010Endodontic Pain in Teeth With Irreversible Pulpitis: A Randomized Controlled Double Blinded Trial","volume":"2","author":"Abdel\u2010Hamid L. 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