Protocol registration and study design
Ethical approval was obtained from Institutional Ethics Committee (SVIEC/ON/DentBNPG18/D19020) and registered in Clinical Trial Registry India (CTRI/2020/09/027635), and written informed consent was obtained from each participant. This study was a randomized, controlled, single-center clinical trial with parallel experimental groups.
Patient selection
Inclusion criteria were healthy individuals and patients with stage 1 hypertension (systolic pressure -130 to 139 mm Hg or a diastolic pressure -80 to 89 mm Hg) and stage 2 hypertension (systolic pressure of 140 mm Hg or higher or a diastolic pressure of 90 mm Hg or higher) for hypertension group[20];between 18 to 60 years of age showing deep caries; patients having spontaneous and postural pain concerning mandibular molars with preoperative VAS scale of 5 or more on one to 10 point scale, and teeth having delayed response on electric pulp testing. Patients in whom IANB failed to achieve pulpal anesthesia. Patients with known hypersensitivity to diclofenac sodium, ketorolac tromethamine, and lignocaine; with a history of cardiac surgery in the last six months; pregnant or lactating females; tooth with any fracture or visibly crack; developmental anomalies; pathology or open apex related to study teeth; subjects who were taking analgesics or non-steroidal anti-inflammatory medicines that could change their pain perception were excluded from the study.
Sample size estimation
The recruitment of patients for this trial lasted for two years; an average of 2150 individuals with pain were screened. Among these, 198 were selected to participate in this study depending on inclusion and exclusion criteria. The total sample of 198 patients (99 patients per group and 33 per subgroup) with SD 0.5 at 95% confidence interval and 80% power was calculated.
Randomization
After selection, 198 patients were divided into Group 1 (n=99) hypertensive and Group 2 (n=99) healthy individuals. Further co-investigator allocated the subjects into three subgroups by computer randomization using (www.randomizer.org) software. Subgroup 1A/2A: Intraligamentary lignocaine (n=33). 1B/2B: Intraligamentary diclofenac sodium (n=33). Subgroup 1C/2C: Intraligamentary ketorolac tromethamine(n=33). Allocation concealment was done using sequentially numbered opaque sealed envelopes with an allocation ratio of 1:1:1.
Blinding
The entire procedure was double-blinded to avoid bias. The operator and the patient were both blinded by subgroups. The operator received a syringe loaded with the cartridge of either lignocaine, diclofenac sodium, or ketorolac tromethamine with a 27-gauge needle attached to the unit’s tip.
Preparation of Customized cartridge
Customized preparation of cartridges for sodium diclofenac (GCLAM laboratories, Maharashtra, India) and ketorolac tromethamine (Dr. Reddy’s, HP, India) was done. Empty cartridges were procured, autoclaved, and a sterile rubber stopper was placed. NSAIDs drug vials of 30mg/ml were taken and broken from the tip. The sterile 2.5 mL syringe drug was injected into the autoclaved cartridge from the back end (rubber stopper). All aseptic precautions, and voids, if any, were aspirated with a syringe.
A visual analog scale was taken as a parameter to evaluate the pain. It consists of a 10-point scale from no pain (VAS-0) to severe pain (VAS-10). Patients were explained about the same, and pre-operative VAS score was recorded.
Inferior alveolar nerve block
In Group 1, blood pressure was recorded. A conventional nerve block with 1.8 mL of 2% lignocaine without adrenaline (Septodont, Lancaster, United States) was injected. In Group 2, a conventional nerve block with 1.8 mL of 2% local anesthetic agent 1:200000 lignocaine with adrenaline (X-Cain ADR) was injected. Patients were asked to wait till subjective or objective symptoms like tingling and numbness of the lower lip, buccal and lingual mucoperiosteum, followed by tongue. The profoundness of IANB was confirmed by electric pulp testing (Gentle pulse, Parkell Inc., Farmingdale, NY, USA), and those are showing positive responses on pulp testing even after IANB block were given supplemental injection from either of the three groups.
Supplemental injection
A co-investigator loaded the intraligamentary drug of both the groups into the intraligamentary unit (Paroject, Septodont, Lancaster, PA, USA). The intraligamentary syringe loaded with the cartridge of lignocaine with adrenaline (1:200000), diclofenac sodium (30mg/ml), or ketorolac tromethamine with (30mg/mL) with27-gauge needle attached to the tip of the unit. The needle was inserted into the periodontal ligament through the gingival sulcus, between the root surface of the tooth and the alveolar crest, until resistance was encountered. A total of four sites, i.e., axial corners, were selected as the site of injection. Per click, 0.06 mL amount of drug was delivered into the tissues. Approximately 0.4 mL of the drug was injected per tooth. Successful delivery was considered when blanching of the tissue was noticed. A Time interval of 5 minutes’ post-injection was given after intraligamentary to act to its full potential. Later, excavation of caries and access cavity preparation was performed. As soon as the initial drop was achieved to the pulp chamber, again, the intra-operative VAS score was recorded.
Statistical analysis
Paired t-test was used to compare two groups before and after the VAS scale, while one-way ANOVA and Tukey’s Post Hoc test were used to compare the subgroups of group 1 and group 2. Statistical analysis was performed using SPSS software version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) The level of significance was set at p ≤ 0.05.