Hypertonic Saline as a Final Flush and Post-Operative Pain After Single Visit Root Canal Treatment in Mandibular Premolar. (Hypertonic)

Effect of Hypertonic Saline (3%) as a Final Flush Irrigant on Post-Operative Pain and Substance P Expression Following Single-Visit Root Canal Treatment in Patients With Symptomatic Irreversible Pulpitis Related to Mandibular Premolars: A Randomized Controlled Trial

This randomized controlled trial evaluates whether a final flush with 3% hypertonic saline, compared with 0.9% normal saline, reduces post-operative pain and periapical Substance P (SP) levels after single-visit root canal treatment in mandibular premolars with symptomatic irreversible pulpitis. Forty adult patients will be randomized 1:1. Pain will be measured with the Visual Analogue Scale (VAS) at 6, 12, 24, and 48 hours post-operatively. Periapical fluid SP levels will be measured by ELISA at two intra-operative time points (after working length determination, and after the final flush). The number of ibuprofen 400 mg tablets consumed within 24-48 hours will also be recorded.

Study Overview

• Status: Not yet recruiting
• Conditions: Symptomatic Irreversible Pulpitis (SIP)
• Intervention / Treatment: Drug: Normal (0.9%) saline; Drug: Hypertonic 3% saline

Detailed Description

Post-operative endodontic pain is linked to periapical release of Substance P (SP), a neuropeptide that sustains neurogenic inflammation via NK-1 receptor binding. 3% hypertonic saline has documented osmotic decongestant and NF-κB-mediated anti-inflammatory/cytokine-suppressive effects in non-dental models, providing biological rationale for its use as a final irrigant. This is a two-arm, parallel-group, participant- and assessor-blinded RCT conducted at the outpatient endodontic clinic, Faculty of Dentistry, Cairo University. After standardized access, working length determination, and a baseline periapical fluid sample (S1), canals will be shaped with continuous rotary NiTi instrumentation and irrigated with 2.5% NaOCl. After smear layer removal (2.5% NaOCl then 17% EDTA), participants receive a final flush of either 5 mL 0.9% normal saline (control) or 5 mL 3% hypertonic saline (intervention), delivered via a 30-gauge side-vented needle 2 mm short of working length. A second periapical fluid sample (S2) is then collected. Canals are obturated by lateral compaction in the same visit. Participants record VAS pain scores pre-operatively and at 6, 12, 24, and 48 hours, and log ibuprofen 400 mg tablet consumption at 24 and 48 hours. SP will be quantified from S1/S2 samples by ELISA, blinded to group allocation.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kariman Ameen Ismaiel; Phone Number: +201013665586; Email: kariman.ameen@dentistry.cu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-60 years, any sex
• Systemically healthy
• Mandibular premolar with clinically/radiographically diagnosed symptomatic irreversible pulpitis (prolonged, exaggerated response to cold testing; no periapical radiolucency)
• Able to use the VAS scale and complete follow-up

Exclusion Criteria:

• Medically compromised patients
• Pregnant or lactating women
• Allergy/hypersensitivity to local anesthetics or NSAIDs
• Analgesics, anti-inflammatories, or antibiotics within 12 hours pre-treatment
• Vertical root fracture, root resorption, or previous RCT
• Radiographic periapical pathology
• Non-restorable teeth
• TMD, bruxism, or traumatic occlusion interfering with pain assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Normal Saline 0.09; Isotonic, biologically inert final irrigant; mechanical debridement only, no pharmacological activity.	Drug: Normal (0.9%) saline; Isotonic 0.9% NaCl solution used as final canal flush, no pharmacological activity
Experimental: Hypertonic Saline 3%; Isotonic, biologically inert final irrigant; mechanical debridement only, no pharmacological activity.	Drug: Hypertonic 3% saline; Osmotic/anti-inflammatory final irrigant hypothesized to reduce periapical edema and suppress pro-inflammatory cytokine-mediated SP release via NF-κB pathway inhibition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative pain intensity at 6 hours	Visual Analogue Scale (VAS), 0-10 (0 = no pain, 1-3 mild, 4-6 moderate, 7-10 severe)	6 hours post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative pain intensity at 12, 24, and 48 hours	VAS, 0-10, same categorization as primary	12, 24, and 48 hours post-operatively
Change in periapical Substance P expression (ΔSP = S2 - S1)	Quantified by ELISA (human Substance P kit) from periapical fluid collected via paper point; pg/mL	S1 = after working length determination (intra-operative); S2 = immediately after final flush (intra-operative)
Number of rescue analgesic tablets consumed	Ibuprofen 400 mg tablets, patient-recorded tablet-count chart, max 3 tablets/24 h	24 and 48 hours post-operatively

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Hypertonic saline; Root canal irrigation; Substance P; Post-operative endodontic pain; Mandibular premolar; Single-visit root canal treatment
• Additional Relevant MeSH Terms: Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride
• Other Study ID Numbers: ENDO 3.3.3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No