Success Rate of 4 Injection Protocols for Mandibular First Molars With Symptomatic Irreversible Pulpitis: A CONSORT Randomized Triple-blind Clinical Trial
Phase: NA
Conditions: Root Canal Infection
Sponsor: Ain Shams University

Title: Efficacy of four local anesthesia protocols for mandibular first molars with symptomatic 
irreversible pulpitis. A randomized clinical trial 
NCT number: NCT04929522 
Date: 5-October- 2021  
Subjects and methods 
Ethical considerations 
This trial was conducted with the approval of the institutional review of board (IRB) of the ethics 
committee at the Faculty of Dentistry, Ain Shams University, Cairo, Egypt (FDASU-REC772019). 
The protocol was registered at the clinical trials website (http://www.clinicaltrials.gov, ID: 
NCT04929522). Subjects were treated in full compliance with the World Medical Association 
Declaration of Helsinki (2008).  
Trial design  
This study was designed as a prospective, parallel, triple blinded, and randomized clinical trial with an 
allocation ratio of 1:1. The trial design is being reported according to the Preferred Reporting Items 
for Randomized Trials in Endodontics (PRIRATE) 2020 guidelines (Nagendrababu et al. 2020).  
Sample size calculation  
A sample size calculation was performed based on the study by Kanaa et al. (2012). This research 
was based on a type I error of 0.05 and a power of 0.8 and indicated that ideally, a sample size of 36 
in each group would be required to detect a 20% difference in the success rate of the test groups. To 
increase the validity of the study, 40 subjects in each group were considered.  
Eligibility criteria  
Patients who participated in this trial were allocated from the outpatient emergency clinic of the 
Endodontic Department, Faculty of Dentistry, Ain Shams University in Cairo, Egypt, between 
January 1st, 2021, and May 30th, 2021. All the patients were informed about the benefits, risks, and 
indications for endodontic treatment and possible adverse effects of the proposed interventions. All 
the included patients signed a written informed consent. 
Inclusion criteria 
Patients included in the study were healthy males and females (Category: American Society of 
Anesthesiologists class 1) aged 21-49 years, with no physical disability, facial paresthesia, or 
psychological problems, presenting with a mandibular first molar, with signs and/or symptoms of 
symptomatic irreversible pulpitis.  
Exclusion criteria  
Pregnant women, patients who took analgesics or other medications that would alter the inflammatory 
response of the pulp or provide analgesia 12- hours pre-operatively, those with known sensitivity to 
the pharmaceuticals used in this trial were excluded from the study. Also, those with pathological 
periodontal pockets more than 3 mm depth at the injection site were excluded.  
Randomization and blinding  
Participants were allocated randomly into four groups with1:1 allocation ratio to ensure random 
selection by using computer-generated randomization (www.randome.org). The sequence was 
therefore generated. 
Allocation concealment mechanism: The sequentially generated numbers were placed in opaque 
envelopes until the intervention was conducted. Each participant was asked to select an envelope that 
determines which group of intervention was assumed.  

Implementation: The co-researcher used computer-generated randomization for participants who 
achieve eligibility criteria. Accordingly, participants were enrolled in either of the groups under study. 
The participants, the operator who initiated endodontic treatment, monitored the pain and heart rate, 
and the statistician were blinded to the anesthetic techniques.  
Intervention  
The diagnosis was confirmed through history reporting spontaneous pain, a moderate to a severe 
painful response that persists after thermal stimulation, a prolonged response to cold testing with 
Endo-Ice (1,1,1,2 Tetrafluoroethane; Hygenic Corp, Akron, OH), absence of percussion sensitivity, 
and the periapical aspect of the tooth in the bidimensional periapical radiograph was normal. 
Matching vital contralateral teeth were also tested to ensure an accurate diagnosis and to serve as 
controls. To prevent bias, this diagnostic step was performed by one investigator (AH). In contrast, 
another investigator (DK) was responsible for administering all anesthetic injections. A third 
investigator (SS) was responsible for root canal treatment procedures, pain recording and monitoring 
of heart rate. All investigators have a minimum of 12 years of clinical experience in endodontics.  
One hundred and eighty-five patients consecutively visited were assessed for eligibility. Twenty-five 
patients were excluded for different reasons, and the others 160 (eighty-four female and seventy-six 
male patients) were allocated to the trial and randomly assigned into four groups (n=40) as follows 
(Figure 1):  
Group 1 (IANB): After determining the injection site and aspiration, 3.6ml of the anesthetic solution 
was administered using the standard inferior alveolar nerve block (IANB) injection. This was 
considered the control group. 
Group 2 (IANB + IO): A standard IANB was administered using 1 carpule (1.8 ml) of the anesthetic 
solution followed by another carpule (1.8 ml) using the supplemental intraosseous infusion (IO) 
injection with the Anesto system (W&H Dentalwerk Bürmoos, Austria). To ensure comfort during the 
procedure, 0.1ml of the anesthetic solution was infiltrated at the perforation site using the standard 
syringe. The perforation site was selected near the junction of the attached and unattached gingival 
tissues, immediately distal to the first molar. Perforation was accomplished by operating the Anesto 
handpiece at full speed, with constant moderate pressure maintained until the perforator was felt to 
‘drop’ into the cancellous bone. The anesthetic solution was then deposited over 60 seconds. The 
Anesto handpiece was again retracted and, with the perforator rotating, removed from the injection 
site. Group3(IANB+PDL):AstandardIANBwasadministeredusing1carpule(1.8ml)ofthe anesthetic 
solution, followed by another carpule (1.8 ml) using the supplemental periodontal ligament (PDL) 
injection. The needle was wedged with force into the PDL space between the tooth and the alveolar  
crest of the bone, at 30-degrees to the long axis of the tooth. The thumb and index fingers of the left 
hand supported the needle to prevent buckling. The handle of the syringe was squeezed firmly until 
backpressure was achieved. The anesthetic solution was injected mesially and distally to the treated 
molar.  
Group 4 (IANB + BI): A standard IANB was administered using 1 carpule (1.8 ml) of the anesthetic 
solution, followed by another carpule (1.8 ml) using the supplemental buccal infiltration at the buccal 
side of the affected tooth. The anesthetic solution was injected halfway to the mesiodistal width of the 
clinical crown.  
IANB, PDL, and BI injections were performed with a conventional aspirating dental syringe 
(Patterson Dental Co, Montana, USA) and a 27-G needle at a rate of 1.8 mL/min. The anesthetic 
solution used for all techniques was Articaine HCL 4% with 1:100,000 adrenaline (Artinibsa, Inibsa, 
Barcelona, Spain).  
 

Outcome assessment  
Anesthesia was confirmed 15 minutes post-injection by the following responses: (1) confirmation of 
lip numbness, (2) negative response to Endo-Ice, (3) negative response to the maximum output of the 
electric pulp tester (Parkell, Edgewood, NY, USA). Root canal treatment procedure was later 
initiated. The patients were asked to rate their pain score once using a verbal rating scale (VRS) from 
0 to 3. The pain was scored as follows: Score 0, no pain; Score 1, mild pain; Score 2, moderate pain; 
or Score 3, severe pain. After rubber dam placement and during caries removal, access preparation, 
and pulpectomy, the success of the anesthetic technique was determined by VRS. The technique was 
considered as a ‘success’ when the patient reported no pain (VRS = 0 or 1) and as a ‘failure’ 
otherwise (VRS >1).  
Heart rate changes were monitored with a finger pulse oximeter (Medlinket, Shenzhen Med-link 
Electronics, Shenzhen, China). It was recorded from 2 min before to 5 min after injection, at 30-s 
intervals.  
Statistical analysis  
All analyses were undertaken with IBM SPSS Statistics (SPSS 26.0; SPSS Inc., Chicago, IL). The 
anesthetic success rates were analyzed using the chi-square test. Age differences were analyzed using 
One Way ANOVA; gender differences were analyzed using the Fischer Exact test, while heart rate 
changes were analyzed with the Kruskal Wallis test, being non-normally distributed. Statistically 
significant differences were set at the P < 0.05 level.  
Results 
Every tested contralateral teeth used as control, responded positively to the thermal and electrical pulp 
testing during the diagnostic phase. All the participants had a positive lip sign (numbness) and a 
negative response to thermal and electrical testing 15 minutes post-injection of all techniques and 100% 
of the anaestethic block was considered effective. No supplemental anaesthetic infiltration was 
administrated. No paresthesia or adverse effects associated with the use of Articaine IANBs were found 
in this trial.  
Table 1. shows the distribution of the participants. There were no differences in the success rate related 
to the age or gender (P > 0.05) so the participants were homogenously distributed among the study 
groups.  
Table 2 represents the anesthetic efficacy of the different tested injection protocols. IANB +IO injection 
had a statistically higher success rate 92.5% (p>0.05), followed by IANB + PDL injection (72.5%), 
IANB + BI injection (65.0%), respectively with no statistical differences between them (p<0.05). In 
comparison, IANB injection alone had a success rate of (40%) which was statistically the lowest 
compared to other techniques (p>0.05). 

An increase in the heart rate was noted in patients who received IANB + IO injection, and this was 
statistically significant compared to the other injection techniques (p>0.01). Differences in heart rate 
changes among the other injection technique were non-significant (P < 0.05). Relative risk values are 
reported in Table 2. The relative risk for all the supplemental anaesthesia techniques was less than 1 
indicating that the risk of the outcome (high VRS numbers) was decreased by using supplemental 
anaesthesia protocol. The actual difference in the observed risk of events between the experimental and  
IANB (Control) techniques is shown in Table 2. The risk in the intervention group was decreased 
between 25 and 52% by using supplemental anaesthesia. 
Table 1. Demographic data of the patients for each anaesthetic group. 
 
 
 
 
 
IANB 
n = 40 
IANB+IO 
n = 40 
IANB+PDL 
n = 40 
IANB+BI 
n = 40 
P-value 
Gender n (%) 
Female 
Male 
 
25 (62.5%) 
15 (37.5%)  
 
28 (70%) 
12 (30%) 
 
26 (65%) 
14 (35%) 
 
23(57.5%) 
17 (42.5%) 
0.740 
Age (Mean SD) 
29  9.1 
31  6.8 
33  5.5 
29  8.2 
0.055 
 
Table 2: Success and failure rates for the four local anaesthesia protocols.  
 
Group 
Success 
n(%) 
Failure 
n(%) 
OR 
[95% CI] 
Relative risk 
[95% CI] 
Risk difference 
IANB (control) 
16(40%) a 
24(60%) 
--- 
--- 
--- 
IANB +IO 
37(92.5%) c 
3(7.5%) 
0.05[0.01-0.21] 
0.13[0.04-0.38] 
-0.52 
IANB + PDL 
29(72.5%) b 
11(27.5%) 
0.25[0.10-0.65] 
0.46[0.26-0.81] 
-0.32 
IANB + BI 
26(65.0%) b 
14(35.0%) 
0.36[0.15-0.89] 
0.58[0.36-0.95] 
-0.25 
Different superscript letters indicate a statistically significant difference within the same vertical 
column (p > 0.05)