Effect of calcium hydroxide vs. tobradex intracanal medicament on postoperative endodontic pain: a pragmatic prospective study

Abstract

This pragmatic study provides preliminary evidence on the effectiveness of calcium hydroxide (Ca(OH)₂) and Tobradex (a tobramycin–dexamethasone combination) as intracanal medicaments for managing postoperative pain following emergency root canal treatment in patients with symptomatic irreversible pulpitis. Forty-three adults participated (27 received Ca(OH)₂ and 16 received Tobradex). Pain intensity was evaluated using a numeric rating scale before treatment and at 24 and 48 h postoperatively. Both groups showed significant pain reduction at 24 h, but Tobradex produced a greater and faster decrease (mean pain reduction from 7.69 ± 3.68 to 1.31 ± 2.36; P < 0.001) compared to calcium hydroxide (median reduction from 7.0 to 2.0; P = 0.006). No further improvement occurred between 24 and 48 h for either group, and demographic factors had no significant influence. Overall, Tobradex demonstrated superior short-term analgesic efficacy, indicating that corticosteroid–antibiotic combinations may enhance postoperative comfort more effectively than calcium hydroxide in endodontic emergency cases.

Trial registration

The study protocol was retrospectively registered in Clinicaltrials.gov on 13th of Jan. 2026, with ID number NCT07332936.

Introduction

Postoperative endodontic pain is a common issue in daily dental practice, even after emergency root canal treatment [1]. Up to 80% of patients experiencing endodontic emergencies report significant pain before the procedure, and many continue to feel some level of discomfort afterward [2] Effectively managing this inter-appointment pain is crucial for ensuring patient comfort and satisfaction [3]. Calcium hydroxide is one of the most commonly used intracanal medicaments due to its strong antimicrobial properties and high pH [3–5]. However, its effectiveness in alleviating pain is questionable; there is no definitive evidence that calcium hydroxide significantly reduces pain after treatment [3]. In fact, it may even provoke or prolong inflammation and discomfort in some cases. Previous studies have suggested that calcium hydroxide offers no greater pain relief than not using any intracanal medicament at all. Furthermore, if calcium hydroxide is extruded beyond the apex of the tooth, it can irritate the peri-radicular tissues, leading to severe pain and tissue damage [6, 7]. These limitations underscore the need for alternative intracanal medications that focus on pain reduction.

Antibiotic–corticosteroid combinations have been advocated as intracanal dressings to control inflammation and pain in endodontic therapy [8]. Ledermix paste, which contains the antibiotic demeclocycline and the steroid triamcinolone, has demonstrated the ability to diffuse through dentinal tubules into periapical tissues, thereby reducing inflammation [9, 10]. Clinical studies have shown that Ledermix (antibiotic/steroid) provides superior early postoperative pain relief compared to calcium hydroxide and other intracanal medicaments [6, 11], highlighting the significant role of intracanal steroids in short-term pain control [8].

Tobramycin, an aminoglycoside antibiotic, when combined with a corticosteroid such as dexamethasone, represents a similar pharmacological approach aimed at achieving both antimicrobial and anti-inflammatory effects [12, 13]. Tobradex (tobramycin 0.3% + dexamethasone 0.1%) is a commercially available formulation with an established safety profile in clinical use (ophthalmology), and its components have well-documented mechanism relevant to endodontic inflammation control [14]. Although no previous studies have directly evaluated Tobradex as an intracanal medicament, its selection in the present study was based on extrapolation from existing evidence supporting corticosteroid-antibiotic combinations, along with its pharmacological rationale. Therefore, its use in this study was considered exploratory and aimed at assessing its potential effectiveness in reducing postoperative endodontic pain.

This present study aimed to evaluate and compare the effectiveness of Calcium hydroxide and Tobradex (intracanal medicaments) for reducing pain after emergency root canal treatment at 24 and 48 h in patients with symptomatic irreversible pulpitis. A secondary goal was to explore potential links between pain relief and patient demographic factors such as age and gender.

Materials and methods

This study was designed as a pragmatic prospective observational comparative study conducted in an emergency endodontic setting to compare the effectiveness of two inter-appointment intracanal medicaments in reducing postoperative endodontic pain: calcium hydroxide (used as a control) and a combination of the antibiotic tobramycin and the steroid dexamethasone.

The study protocol received approval from the Umm Al-Qura University biomedical research ethics committee (HAPO-02-K-012-2023-05-1631), registered retrospectively on the 13th of Jan. 2026 in clinicaltrials.gov (NCT07332936), and all participants provided informed written consent in accordance with the Declaration of Helsinki. The study protocol was registered retrospectively due to the pragmatic nature of patient recruitment in an emergency clinical setting. Although prospective registration is preferred, retrospective registration was performed to ensure transparency and accessibility of the study protocol.

Although randomization was initially planned, it was not feasible to implement because patients presented as emergency cases, requiring immediate treatment. Additionally, the availability of intracanal medicaments varied during the clinical sessions. Consequently, treatment allocation was determined by medicament availability at the time of treatment, resulting in unequal group sized. Loss of follow-up occurred but was limited and did not substantially influence group distribution.

This study involved medically fit adult patients presenting with symptomatic irreversible pulpitis, with or without symptomatic apical periodontitis (diagnosed based on clinical findings including percussion and/or palpation), requiring emergency endodontic intervention. Any medically compromised patients (e.g., uncontrolled diabetes, immunocompromised status), known allergies to relevant materials (e.g., corticosteroids, tobramycin, calcium hydroxide), teeth previously treated endodontically, those with acute or chronic apical abscesses requiring systemic antibiotics, and pregnant or lactating women were excluded from the study to ensure a homogeneous study population. Sample size was calculated based on a previously reported effect size (Cohen’s d = 0.84) for postoperative pain reduction between calcium hydroxide and steroid–antibiotic medicaments [15]. A total of 46 participants were required to achieve 80% power at α = 0.05 using the Mann–Whitney test. Recruitment of participants took place from the 1st of July 2023 to the 30th of June 2024. The final sample comprised 43 patients (27 in calcium hydroxide and 16 in tobramycin/dexamethasone groups) due to missing participants during follow-up and recall for pain evaluation. While patients were blinded to the treatment, the endodontists were not. Pain intensity was self-reported using a numeric rating scale (0–10) before treatment and at 24 and 48 h postoperatively. Pain ratings and assessment were recorded via a form (either in clinic or via telephone) conducted by a calibrated examiner who was not involved in treatment. No specific post-operative analgesic regimen was prescribed. Patients were allowed to use over-the-counter medications if required; however, the type, dose, and timing of analgesic used were not systematically recorded.

All patients underwent a standardized emergency endodontic treatment, starting with local anesthesia (2% Mepivacaine with 1:100,000 epinephrine) and isolation of the affected tooth using a rubber dam. A conservative access cavity was created, and the canal orifice was located. The working length was established using with a #10 K-file and the Root ZX dental apex locator (J. Morita, Japan) and verified with a radiograph. Canal preparation was performed using ProTaper Next rotary files (X1 and X2) (ProTaper Next, Dentsply Sirona, Charlotte, North Carolina, United States), corresponding to a standardized preparation approach typically reaching an apical size of 25 with variable taper depending on canal anatomy. Irrigation was performed using 5.25% sodium hypochlorite (Diaa Dental Products, Saudi Arabia), followed by a final flush with 17% EDTA solution (Diaa Dental Products, Saudi Arabia), and then dried with sterile paper points. No adjunctive irrigation activation technique was used in this study. Based on group assignments, the intracanal medicament was applied: the control group received calcium hydroxide paste (METAPEX Plus, META BIOMED, Korea) using the syringe and lentulo spiral (Paste carrier 25 mm, MANI, KSA), while the intervention group was treated with Tobramycin 3 mg/ml with Dexamethasone 1 mg/ml (Tobradex, Novartis, New Jersey, USA), delivered through a BD Ultra-Fine insulin syringe (Becton Dickinson, New Jersey, USA) with thorough distribution aided by a sterilized endodontic gutta-percha point. Approximately 0.1–0.2 mL (several drops) of the solution was dispensed into each canal. After placing the medicament, a cotton pellet was placed over the canal orifices, followed by a base layer of Cavit (3 M, MN, USA) applied into the access cavity. This layer was then covered and reinforced with a layer of glass ionomer cement (GIC) (Fuji IX GP^®, GC, IL, USA) to create a secure double seal. This method aimed to prevent microleakage and to hold the intracanal medicament in place during the period between appointments. Patients were scheduled to complete root canal treatment in a subsequent visit. The observation period for pain was limited to the first 48 h following the initial emergency treatment.

Data analysis was conducted using SigmaPlot version 14.5 (Systat Software Inc., USA), focusing on pain intensity scores recorded at baseline, 24 h, and 48 h for two medicament groups: tobramycin and calcium hydroxide. A significance level of α = 0.05 was established for all tests. Within-group comparisons revealed that the tobramycin group met the assumptions of normality (P = 0.227) and homogeneity of variances (P = 0.539), allowing for a one-way repeated-measures ANOVA, coupled with Bonferroni-adjusted pairwise multiple comparisons to identify significant differences. Conversely, the calcium hydroxide group showed normal distribution (P = 0.179) but did not meet the equal-variance assumption (P < 0.05); therefore, Friedman repeated-measures ANOVA on ranks was used and followed by Tukey post-hoc tests. When groups were compared, Mann–Whitney rank-sum tests were used to assess percentage reduction in pain at 24 and 48 h, due to non-normality (Shapiro–Wilk P < 0.05). The same test was utilized to investigate how gender (male versus female) affects the percentage reduction in pain at both time intervals. Additionally, Spearman’s rank-order correlation was utilized to explore the relationship between patient age and percentage change in pain at both time intervals. Given the unequal group sizes and non-normal data distribution, non-parametric statistical methods were employed where appropriate to ensure robustness of the analysis. The manuscript was prepared in accordance with the STROBE guidelines for observational studies.

Results

A total of 43 patients participated in the study, consisting of 24 females (55.8%) and 19 males (44.2%). The average age of the participants was 33.4 ± 8.2 years (range 20–50 years). Among the patients, 27 were treated with Calcium Hydroxide, while 16 received Tobradex as their intracanal medicament (Table 1).

Table 1.

Baseline demographic and clinical characteristics of the study participants

Characteristic	Calcium Hydroxide (n = 27)	Tobradex (n = 16)	P value*
Age (years), mean ± SD	33.1 ± 8.4	33.9 ± 8.0	0.74
Gender, n (%)
Male	12 (44.4)	7 (43.8)	0.97
Female	15 (55.6)	9 (56.2)
Baseline pain score (NRS), median (IQR)	7.0 (2.0–10.0)	7.5 (5.0–10.0)	0.68

SD Standard deviation

NRS Numeric Rating Scale (0–10)

IQR Inter-quartile range

Within-group comparisons

Tobradex

The one-way repeated-measures ANOVA showed a significant difference in mean pain scores across various time points (F (2, 30) = 29.672, P < 0.001). The mean ± SD pain scores were 7.69 ± 3.68 at the initial visit, 1.31 ± 2.36 after 24 h, and 2.38 ± 2.94 after 48 h. Post-hoc Bonferroni tests revealed significant reductions in pain from baseline to 24 h (P < 0.001) and from baseline to 48 h (P < 0.001), but the difference between 24 and 48 h was not significant (P = 0.721) (Fig. 1).

Fig. 1.

Changes in pain scores over time for Tobramycin and Calcium Hydroxide groups. * Significant differences (P < 0.001), **Significant differences (P < 0.05)

Calcium hydroxide

The Friedman test identified a significant difference in median pain scores across the three time points (P = 0.004). The median (IQR) pain scores decreased from 7.0 (2.0–10.0) at baseline to 2.0 (0–4) after 24 h and 3.0 (0–5) after 48 h. Tukey post-hoc analysis showed a significant reduction from baseline to 24 h (P = 0.006), but no significant differences from baseline to 48 h (P = 0.158) or between 24 h and 48 h (P = 0.438) (Fig. 1).

Between-group comparisons

When comparing the percentage reduction in pain between both groups: After 24 h, the Mann–Whitney rank-sum test showed a statistically significant difference (P = 0.017), with a greater median reduction in the Tobradex group (median = − 100%, IQR = − 100 to − 95%) compared to the calcium hydroxide group (median = − 95%, IQR = − 99 to 0%). After 48 h, the difference between the groups was not significant (P = 0.081) (Table 2).

Table 2.

Postoperative pain scores and percentage pain reduction by intracanal medicament

Outcome	Calcium Hydroxide (n = 27)	Tobradex (n = 16)	P value*
Baseline pain score (NRS), median (IQR)	7.0 (2.0–10.0)	7.5 (5.0–10.0)	0.68
Pain score at 24 h, median (IQR)	2.0 (0–4)	1.0 (0–2)
Pain score at 48 h, median (IQR)	3.0 (0–5)	2.0 (0–4)
Percentage pain reduction at 24 h, median (IQR)	−95% (− 99 to 0)	−100% (− 100 to − 95)	0.017
Percentage pain reduction at 48 h, median (IQR)	−90% (− 100 to − 50)	−95% (− 100 to − 75)	0.081

NRS Numeric Rating Scale (0–10)

IQR Inter-quartile range

Gender and age effects

Regarding gender, the Mann–Whitney test showed no significant difference in percentage reduction in pain between females (median = − 98%, IQR = − 100 to 0%) and males (median = − 95%, IQR = − 100 to − 90%) at either time point (P = 0.623). Finally, Spearman’s correlation revealed no significant association between age and pain reduction at 24 h (ρ = −0.091, P = 0.560) or at 48 h (ρ = −0.201, P = 0.196).

Discussion

The main goal of this study was to analyze and compare the effects of tobramycin–dexamethasone paste (Tobradex) and calcium hydroxide on pain reduction over time after emergency root canal treatment, and to determine if patient-related factors contribute to pain reduction. Intracanal medicaments led to significant pain relief within the first 24 h. However, the group receiving tobramycin experienced a quicker and more notable decrease in pain compared to the calcium hydroxide group, and this difference was statistically significant at 24 h. The relatively high variability in pain scores observed in the Tobradex group may be attributed to individual differences in pain perception and response to treatment, which are commonly reported in clinical pain studies. Additionally, neither gender nor age significantly influenced the level of pain improvement.

Our finding that a corticosteroid-containing intracanal medicament yields faster pain relief aligns with previously published evidence. One of the studies reported that an intracanal corticosteroid–antibiotic compound significantly and rapidly reduced post-treatment pain compared to a placebo, with no noted pain recurrence or adverse effects [16]. Another study found that teeth treated with Ledermix paste (a combination of triamcinolone acetonide corticosteroid and demeclocycline antibiotic) experienced significantly less postoperative pain than those receiving calcium hydroxide or no medicament [17]. A recent clinical investigation has also reinforced the efficacy of antibiotic–steroid intracanal dressings in relieving pain, where they found that Ledermix paste resulted in the highest pain reduction among various medicaments tested, including calcium hydroxide and triple antibiotic paste, achieving significantly lower pain scores at 24–72 h compared to the calcium hydroxide group [18]. These findings emphasize the rapid action of intracanal steroids on inflamed periradicular tissues. Given this context, the use of a tobramycin–dexamethasone formulation (Tobradex) appears to be a logical extension of the same principle. To our knowledge, no published study has specifically examined Tobradex as an intracanal medicament for endodontic pain; however, the strong early analgesic effect noted in our study is consistent with trends reported for other steroid-containing pastes [8]. This new finding shows that using available ophthalmic steroid–antibiotic medication for intracanal use during root canal treatment is both feasible and effective in managing postoperative pain.

The superior performance of the tobramycin–dexamethasone formulation within the first 24 h can be attributed to the potent anti-inflammatory action of dexamethasone, a corticosteroid that inhibits the release of inflammatory mediators such as prostaglandins and bradykinin by blocking the arachidonic acid cascade. This action significantly reduces periapical inflammation and pain [19]. While corticosteroids are not traditional analgesics, their capacity to diminish inflammation in periradicular tissues results in notable pain relief during the acute post-treatment phase [3, 19]. A meta-analysis supports this, indicating that adjunctive corticosteroid use notably decreases endodontic pain within 4–6 h and up to 12 h after treatment [20]. In our study, the Tobradex group’s mean pain score approached zero by the 24-hour mark, highlighting the steroid’s effectiveness in moderating the postoperative inflammatory response. The inclusion of tobramycin, a broad-spectrum aminoglycoside antibiotic, aids in eliminating residual bacteria within the canal, providing an additional defense against microbial regrowth and potential flare-ups [15]. Overall, intracanal medicaments serve a dual purpose as both antimicrobial agents and physical barriers to prevent bacteria from re-entering the canal between appointments. Therefore, the combination of corticosteroids for inflammation control and antibiotics for infection management addresses both key factors contributing to post-operative pain in endodontics [16].

Calcium hydroxide (Ca(OH)₂) has a gradual and modest pain-reducing effect, primarily valued in endodontics for its high pH and antimicrobial properties, which can neutralize lipopolysaccharide endotoxins and combat various pathogens [7]. However, it lacks a direct anti-inflammatory mechanism and may cause transient irritation in periapical tissues [7]. Studies indicated no clear evidence that Ca(OH)₂ reduces pain effectively when used alone as an intracanal medicament [3, 6]. While some studies found it did not significantly outperform an empty canal in pain reduction [17], others reported a modest benefit in reducing pain with its use [21]. In our study, the Ca(OH)₂ group showed a significant pain decrease at 24 h (median NRS from 7/10 to 2/10), but by 48 h, pain levels stabilized (median 3/10) or even slightly increased, indicating that its effectiveness diminishes over time and cannot suppress any residual inflammatory exudate or irritants might continue to cause discomfort until the body’s natural healing progresses [7]. The stabilization or slight increase in pain between 24 and 48 h may reflect the natural inflammatory response following treatment or the gradual reduction of the medicament’s anti-inflammatory effect. Conversely, a steroid-based medicament may provide better immediate pain relief by continuously inhibiting inflammation [19]. Overall, while Ca(OH)₂ is essential for microbial control and hard tissue formation, it is less effective than corticosteroids for immediate pain management.

One notable aspect of our results is that patient-related factors, such as gender and age, did not have a significant impact on pain outcomes. Both men and women patients experienced similar benefits from the intracanal medicaments, and younger and older adults reported equivalent pain relief at both the 24 and 48-hour marks. The literature concerning gender differences in endodontic pain presents inconsistent findings. Some studies with large sample sizes have reported that women experience a higher incidence of severe post-treatment pain compared to men. Additionally, older patients sometimes report more pain than middle-aged adults [22]. The biological pain perception and pain-reporting behaviors may explain these differences [22]. However, other studies have found no significant predisposition related to gender or age, particularly when effective analgesic or treatment interventions are utilized [23]. Our findings align with the latter perspective; the significant pain relief provided by both medicaments, especially Tobradex, likely outweighed any minor differences in pain sensitivity among individuals.

Limitation

Several limitations should be noted when assessing the findings of this study. Firstly, the non-randomization nature of the study. Although it was designed prospectively, however randomization was not feasible due to immediate intervention required for the patients presented to the emergency clinic. This pragmatic approach reflects real-world emergency endodontic practice but may introduce selection bias.

The relatively small sample size and unequal distribution may limit statistical power and increase the risk of both type I and type II errors. Although appropriate statistical methods were used to account for these limitations, the findings should be interpreted with caution. These characteristics are inherited to the pragmatic design of the study but may affect the precision and generalizability of the results. Furthermore, the observation period was limited to 48 h, focusing on the acute post-operative pain phase. This timeframe is clinically relevant to post-operative endodontic pain; however, longer periods may be needed to assess the effect of the medicament used. In addition, certain clinical variables, including tooth type, duration of preoperative pain, and distribution of symptomatic apical periodontitis between groups were not recorded and may represent potential confounding factors influencing postoperative pain outcome.

In addition, participants were allowed to use over-the-counter analgesics; however, the type, dosage, timing, and frequency were not recorded. Given that pain was the primary outcome, this represents a significant uncontrolled confounder that may have influenced the observed pain reduction and limits the ability to attribute outcomes solely to the intracanal medicaments.

Finally, the generalizability of the study may be limited since this was a single-centre study. Multicentre randomized trials with larger sample size and extended follow up periods may be required. Despite these limitations, this study provides the first prospective clinical evidence supporting short term analgesic effect of tobramycin-dexamethasone intracanal medicament.

Conclusion

Both Calcium hydroxide and Tobradex intracanal medicaments provided significant pain relief within the first 24 h after the initial emergency root canal treatment. However, tobramycin showed a quicker and more noticeable reduction in pain compared to calcium hydroxide at the 24-hour mark. The findings suggest that the adjunctive use of corticosteroid–antibiotic combinations may offer superior short-term pain control in endodontic emergencies. Given the observational design and methodological limitations, these findings should be interpreted as preliminary and hypothesis-generating. Further randomized controlled trials are required to confirm the observed effects.

Abbreviations

Ca(OH)₂

Calcium Hydroxide

EDTA

Ethylenediameinetetraacitic Acid

GIC

Glass Ionomer Cement

NRS

Numeric Rating Scale

IQR

Interquartile Range

SD

Standard Deviation

Authors’ contributions

F.A.: Conceptualization, Investigation, Resources, Project administration; S.O.: Data curation, Investigation, Resources; A.B.: Conceptualization, Data curation, Investigation, Resources, Project administration, Validation, Visualization, Writing – review & editing; A.A.: Conceptualization, Data curation, Formal analysis, Investigation, Resources, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing.

Funding

This project received no funding.

Data availability

All data related to this project are presented within this manuscript.

Declarations

Ethics approval and consent to participants

The study protocol received approval from the Umm Al-Qura University biomedical research ethics committee (HAPO-02-K-012-2023-05-1631), registered retrospectively on the 13th of Jan. 2026 in clinicaltrials.gov (NCT07332936), and all participants provided informed written consent in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.