Mepivacaine-Tramadol on the Success of Inferior Alveolar Nerve Block in Symptomatic Irreversible Pulpitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the success of inferior alveolar nerve block, after the local application of Mepivacaine plus Tramadol in patients with symptomatic irreversible pulpitis. Also, to evaluate the duration of the anesthetic effect when using Mepivacaine plus Tramadol in the same anesthetic technique and patients group. Hypothesis: Local application of mepivacaine plus tramadol increases the successful of inferior alveolar nerve block in patients with irreversible pulpitis.

Detailed Description
-----------------
The treatment of pain is an integral part of Endodontics, this must be controlled before, during and after treatment. The inferior alveolar nerve block is the most common anesthetic technique used in mandibular teeth during endodontic treatments. Several studies have reported that it is more difficult to obtain anesthetic success in patients with irreversible pulpitis. There is a 33-80% of failure in the inferior alveolar nerve block in patients with irreversible pulpitis. Some of the more accepted theories for local anesthetic failure establish that inflammation induce tissue acidosis causing ion traping of the local anesthetics enabling the molecules to cross the cell membrane, also inflammatory mediators may sensitize the neurons by interacting with specific receptors leading to periphery sensibilization. Tissue injury may alter the composition, distribution and activity of sodium channels expressed on nociceptors and this may have profound implications in local anesthetic failure. On the other hand, there is a specific group of tetrodotoxin resistant sodium channels four times less sensitive to lidocaine which increase their activity during inflammation. Some ways to control pain is through pharmacological synergism. Tramadol has been proposed as pharmacological adjuvant to local anesthesia and it can improve the anesthetics success and the duration of the anesthetic effect. However, oral administration of drugs can cause adverse systemic effects, and that's why local application is an alternative to increase its concentration on the local damaged tissue reducing the possibility of interactions with other drugs and adverse effects. Another advantage of the combination of Mepivacaine with Tramadol is that it reduces the number of injections in patients and it is less traumatic. Tramadol is centrally acting drug but also a local anesthetic and analgesic effect it has been reported. It acts at multiple sites producing different action mechanisms. Some studies suggest that the use of Tramadol can improve the effect of Mepivacaine in the inferior alveolar nerve block. The blockade of the nervous conduction with Tramadol is 80% more effective if it is compared with some anesthetics like lidocaine. There are few studies evaluating local application of tramadol. In the field of dentistry tramadol using for local anesthetic adjuvant has been studied in oral surgery, so it is important to evaluate it in the field of endodontics to provide better pain management during treatments. Thus, the aim of the study is to evaluate the success of inferior alveolar nerve block with the local application of Mepivacaine plus Tramadol in patients with symptomatic irreversible pulpitis, and also to evaluate the duration of the anesthetic effect when using Mepivacaine plus Tramadol in the anesthetic technique. This study was designed as a double-blind, randomized clinical trial. Following the guidelines suggested by CONSORT group for planning and reporting clinical trials. The ethics committee of the Faculty of Dentistry of San Luis Potosi University approved the study design. All of the subjects will be informed of the possible risk of endodontic therapy and experimental treatments and will sign institutionally approved consents forms. In total 50 patients will be included in this study. The sample size calculation was performed with a Type I error of 0.05 and statical power of 80% using the difference in duration of anesthetic effect between two groups and taking into account previous studies related to the local effect of tramadol in clinical studies where it is used to assess the time of anesthetic effect. All the subjects voluntarily will presented at the Postgraduate Endodontics Clinic of the Faculty of Dentistry at San Luis Potosi University. The select subjects will have a diagnosis of symptomatic irreversible pulpitis in the first and second mandibular molars. The patients will be diagnosing with the cold test and they will indicate their pain scores using numerical rating scale, this is a 11 point scale where the ends points are the extremes of no pain and the worst pain. Accordingly, no pain corresponded with 0, mild pain with 1-3, moderate pain with 4-6 and severe pain 7-10. The control group will receive the inferior alveolar nerve block using 1.8 ml of Mepivacaine 2% epinephrine 1: 100000 and 1.3 ml of Mepivacaine 2% epinephrine 1:100000 mixed with 0.5 ml of Tramadol (50mg/ml) will be used for the anaesthetic blockade in the experimental group. After 15 minutes, the anesthetic blockade will be assessed by a three step examination: lip numbess, positive/negative response to cold testing and clinical discomfort during endodontic access. Inferior alveolar nerve block success will be defined as the absence of pain during any of these evaluations and if patients report pain an analogue visual scale will be used. Statics normal distribution will be tested by the student's t test. A non-parametric chi- squared test was performed to identify statistically differences between the groups; the level of significance was set at p˂ 0.05.

Official Title
-----------------
Efficacy of the Combination Mepivacaine-Tramadol on the Success of Inferior Alveolar Nerve Block in Patients With Symptomatic Irreversible Pulpitis: a Randomized Clinical Trial.

Conditions
-----------------
Symptomatic Irreversible Pulpitis

Intervention / Treatment
-----------------
* Drug: Mepivacaine
* Drug: Mepivacaine plus Tramadol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects diagnosed with symptomatic irreversible pulpitis in the first and second mandibular molars. Exclusion Criteria: Pregnancy Hypersensitivity to local anesthetics and Tramadol Teeth with insufficient tooth structure for restoration, periodontal disease, root resorption, root fracture Systemic diseases: diabetes, uncontrolled hypertension. Patients taking drugs or narcotics. Patients who have used analgesics in the last 8 hours. Patients ingested IMAOS and tricyclic antidepressants 14 days before. Patients ingested carbamazepine (anticonvulsants) Patients in active treatment with ketoconazole and erythromycin.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mepivacaine plus Tramadol<br>1.3 ml of Mepivacaine 2% epinephrine 1:100000 mixed with 0.5 ml of Tramadol (50mg/ml) will be used for the anesthetic blockade in the experimental group | Drug: Mepivacaine plus Tramadol<br>* 0.5 ml of Tramadol mixed with 1.3 ml of Mepivacaine.<br>* Other names: Tradol;|
| Active Comparator: Mepivacaine<br>The control group will receive the inferior alveolar nerve block using 1.8 ml of Mepivacaine 2% epinephrine 1: 100000. | Drug: Mepivacaine<br>* Drug: Tramadol 1.8 ml of Mepivacaine 2% epinephrine 1:100000.<br>* Other names: Dentocaín;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| success of the inferior alveolar nerve block | The anesthetic blockade will be assessed by a three step examination: lip numbess, positive/negative response to cold testing and clinical discomfort during endodontic access. Inferior alveolar nerve block success will be defined as the absence of pain during any of these evaluations and if patients report pain an analogue visual scale will be used. Also, the patient will reported the level of pain in the application of the inferior alveolar nerve block using mepivacaine and mepivacaine plus tramadol and local and systemic side effects will be monitored. | 0-30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anesthetic effect duration | The time of the anesthetic effect will be evaluated in patients in whom anesthetic success is achieved, and also the consume of emergency and rescue post-operative analgesics. Side effects will also be monitored during this period. | 0-14 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anaesthetic effect, Inferior alveolar nerve block, Local tramadol, Mepivacaine, Symptomatic irreversible pulpitis.