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

Int Endod J. 2026 Jul 19. doi: 10.1111/iej.70231. Online ahead of print.

ABSTRACT

AIM: 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.

METHODOLOGY: In this randomized, triple-blind, parallel-arm clinical trial, 124 healthy adults with SIP in a single mandibular molar were randomly allocated (1:1:1:1) to four groups (n = 31): Group FG (trypsin 100 mg/bromelain 90 mg/rutoside 48 mg), Group DF (diclofenac potassium 50 mg), Group PD (prednisolone 20 mg), or Group PB (placebo). One hour after premedication, a standard IANB (1.8 mL 4% articaine, 1:100 000 epinephrine) was administered. The primary outcome was anaesthetic success, defined as the ability to complete endodontic procedures with no or mild pain (NRS ≤ 3). Secondary outcomes included postoperative pain intensity (NRS 0-10) recorded at 6, 12, 24, 48, 72 h, and 7 days, and rescue analgesic intake.

RESULTS: Data of all 124 enrolled patients was analysed. Premedication significantly influenced IANB success (p < 0.001). 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 h compared to the placebo (p < 0.05). There were no significant differences in rescue analgesic intake (p = 0.320) or reported adverse events.

CONCLUSIONS: 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.

CLINICAL IMPLICATIONS: 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.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06298383.

PMID:42473278 | DOI:10.1111/iej.70231