Lidocaine + Clonidine for Intraoral Anesthesia in Patients With Diabetes Mellitus Type 2

Phase 3

Completed

• Conditions: Diabetes Mellitus; Local Anesthesia
• Interventions: Drug: L+C maxillary anesthesia; Drug: L+C mandibular anesthesia; Drug: L+E maxillary anesthesia; Drug: L+E mandibular anesthesia

• Registration Number: NCT02371759
• Lead Sponsor: University of Belgrade

Brief Summary

The purpose of this study is to determine whether 2% lidocaine (L) + clonidine (C) (15 mcg/ml) as a vasoconstrictor achieves efficient (equal or better parameters of intraoral local anesthesia in comparison to 2% lidocaine + epinephrine (E) (1:80 000)) and safe (stable cardiovascular parameters - systolic, diastolic, mean blood pressure and heart rate) intraoral local anesthesia in patients with Diabetes mellitus type 2.

Detailed Description

Patients with diabetes mellitus type 2, represent a risk for performing regional anesthesia techniques due to microvascular (microangiopathy, neuropathy) and macrovascular (hypertension, coronary heart disease) complications. There is evidence that local anesthetic toxicity may be increased in diabetic setting due to underlying neuropathy; while interaction of diabetic blood vessels with vasoconstrictors may be of importance because of microangiopathic changes. Lately, regional anesthesia protocol in general surgery for patients with diabetes mellitus was released, proposing reduction of local anesthetic concentration and avoiding epinephrine as vasoconstrictor.

Oral cavity tissues in diabetes mellitus also suffer from neuropathy (burning, paresthesia, teeth loss, temporomandibular dysfunction, xerostomia) and microangiopathy (periodontal disease, salivary gland dysfunction). Most widely used vasoconstrictor for intraoral local anesthesia, epinephrine, is an alpha- and beta- adrenergic agonist. Because of its beta-adrenergic effects, epinephrine could adversely affect cardiovascular function, especially in risk patients. There are data suggesting that intraoral local anesthesia obtained with 2% lidocaine with clonidine, selective alpha 2-adrenoceptor agonist as a vasoconstrictor, is characterized with significantly more stable cardiovascular parameters and similar parameters of local anesthesia with respect to lidocaine with epinephrine in healthy and hypertensive patients.

With regard to aforementioned, the aim of this randomized double-blind controlled clinical trial is to evaluate and compare efficacy and safety of intraoral local anesthesia obtained with 2% lidocaine (L) + clonidine (15 mcg/ml) (C) or 2% L + epinephrine (1:80 000) (E), comparing healthy and diabetes mellitus type 2 patients. Prior to tooth extraction, random allocation to one of four groups (L+C maxillary infiltration, L+C mandibular block, L+E maxillary infiltration and L+E mandibular block) is performed for diabetic (30 per group) and healthy (30 per group) patients. Parameters of local anesthesia (onset, duration, intensity, width of anesthetic field for maxillary infiltration), cardiovascular parameters (systolic, diastolic, mean arterial pressure; heart rate and electrocardiographic changes), quality of postoperative analgesia (assessed by Visual Analogue Scale, Numerical Rating Scale and number of consumed analgesics) and postoperative complications (infection, bleeding, paresthesia, delayed wound healing) are evaluated and compared.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2015-02-04
• Study First Submitted QC: 2015-02-19
• Study First Posted: 2015-02-26
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Results First Submitted: 2016-12-26
• Status Verified: 2017-03
• Results First Submitted QC: 2017-03-22
• Last Update Submitted: 2017-03-22
• Results First Posted: 2017-05-03
• Last Update Posted: 2017-05-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 256

Inclusion Criteria

• Healthy participants: ASA I
• Diabetic type 2 participants: ASA III (HbA1c level < 9%)
• Required a single-root teeth indicated for non-complicated extraction
• Dental diagnosis of periodontal disease, tooth fracture, chronic periapical lesion and root infection
• Subjects give informed written consent

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Exclusion Criteria

• Pregnancy and lactation
• Allergy to used drugs and food
• Hepatic and/or renal failure
• ASA IV patients
• Tobacco smokers
• History of alcoholism and/or drug abuse and addiction

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Diabetics: L+C maxillary anesthesia	L+C maxillary anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for maxillary infiltration anesthesia
Diabetics: L+C mandibular anesthesia	L+C mandibular anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for mandibular block anesthesia
Diabetics: L+E maxillary anesthesia	L+E maxillary anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%)+ epinephrine (1:80.000) for maxillary infiltration anesthesia
Diabetics: L+E mandibular anesthesia	L+E mandibular anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%) + epinephrine (1:80.000) for mandibular block anesthesia
Healthy: L+C maxillary anesthesia	L+C maxillary anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for maxillary infiltration anesthesia
Healthy: L+C mandibular anesthesia	L+C mandibular anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for mandibular block anesthesia
Healthy: L+E maxillary anesthesia	L+E maxillary anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%)+ epinephrine (1:80.000) for maxillary infiltration anesthesia
Healthy: L+E mandibular anesthesia	L+E mandibular anesthesia	Single dose intraoral local anesthesia with 2ml lidocaine (2%) + epinephrine (1:80.000) for mandibular block anesthesia

Primary Outcome Measures

Name	Time	Method
Baseline Systolic Blood Pressure	Baseline, 0 minutes
Duration of Intraoral Local Anesthesia	Up to 6 hours after local anesthesia injection	Time until cessation in soft tissue numbness
Intensity of Intraoral Local Anesthesia	Up to 10 minutes after local anesthesia injection	Number of participants who reported values \> 0 after pin-prick testing, using Visual Analogue Scale (VAS) and Numerical Rating Scale (NRS). VAS is represented by line 100 mm long, with one end marked with 0 and words "no pain" , while the other end is marked with 100 and words "the worst pain imanginable". VRS scale is represented by line 100 mm long, marked with numbers from 0 to 10, where 0 corresponds to "no pain", and 10 corresponds to "the worst pain imaginable". For both scales, higher scores represent worse outcomes.
Systolic Blood Pressure at 10 Minutes	10th minute	Systolic blood pressure values 5 minutes after local anesthesia injection
Baseline Diastolic Blood Pressure	baseline, 0 minutes
Diastolic Blood Pressure at 15 Minutes	15th minute	Diastolic blood pressure values 10 minutes after local anesthesia injection
Diastolic Blood Pressure at 20 Minutes	20th minute	Diastolic blood pressure values 15 minutes after local anesthesia injection
Diastolic Blood Pressure at 35 Minutes	35th minute	Diastolic blood pressure values 30 minutes after local anesthesia injection
Baseline Values of Heart Rate	baseline, 0 minutes
Heart Rate at 20 Minutes	20th minute	Heart rate 15 minutes after local anesthesia injection, 20 minutes after baseline measurement
Systolic Blood Pressure at 15 Minutes	15th minute	Systolic blood pressure values 10 minutes after local anesthesia injection
Diastolic Blood Pressure at 10 Minutes	10th minute	Diastolic blood pressure values 5 minutes after local anesthesia injection
Heart Rate at 10 Minutes	10th minute	Heart rate 5 minutes after local anesthesia injection, 10 minutes after baseline measurement
Systolic Blood Pressure at 35 Minutes	35th minute	Systolic blood pressure values 30 minutes after local anesthesia injection
Electrocardiogram at 15 Minutes	15th minute	ECG 10 minutes after local anesthesia injection, 15 minutes after baseline measurement
Systolic Blood Pressure at 20 Minutes	20th minute	Systolic blood pressure values 15 minutes after local anesthesia injection
Heart Rate at 15 Minutes	15th minute	Heart rate 10 minutes after local anesthesia injection, 15 minutes after baseline measurement
Ceart Rate at 35 Minutes	35th minute	Heart rate 30 minutes after local anesthesia injection, 35 minutes after baseline measurement
Electrocardiogram at 10 Minutes	10th minute	ECG 5 minutes after local anesthesia injection, 10 minutes after baseline measurement
Baseline Electrocardiogram	baseline, 0 minutes
Electrocardiogram at 20 Minutes	20th minute	ECG 15 minutes after local anesthesia injection, 20 minutes after baseline measurement

Secondary Outcome Measures

Name	Time	Method
Local Postoperative Complications	24 hours, 7 days	Postoperative paresthesia by clinical examination
Onset of Intraoral Local Anesthesia	Up to 10 minutes, until subjective feeling of soft tissue numbnes	Evaluated by pin-prick after subjective feeling of soft tissue numbness appeared after local anesthesia injection
Width of Anesthetic Field After Maxillary Infiltration Anesthesia	Up to 10 minutes after injection of local anesthesia	Soft tissue numbness area determined by pin-prick test after maxillary infiltration anesthesia. Not tested for mandibular ablock anesthesia.
Postoperative Analgesia	up to 24 hours after tooth extraction	Number of participants who experienced postoperative pain, VAS, NRS

Trial Locations

Locations (1)

School of Dental Medicine, University of Belgrade; 🇷🇸 Belgrade, Serbia