Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics

Phase 4

Completed

• Conditions: Cardiac Arrhythmias
• Interventions: Procedure: Lower Third Molar Extraction; Drug: Placebo; Drug: Hyaluronidase

• Registration Number: NCT01719978
• Lead Sponsor: Mauricio Jose Tornelli

Brief Summary

Among the adjuvants to local anaesthetics (LA), the enzyme hyaluronidase is most often used as a diffuser agent of the LA in ophthalmic anaesthesia. It serves to improve clinical efficacy and prolong anaesthesia as an alternative to long-lasting and potentially more dangerous LA, especially in patients with increased cardiovascular risk. There is scarce clinical data about the safety of the use of hyaluronidase in dental procedures.

This study aimed to compare hemodynamic and electrocardiographic variables during a dental surgical procedure using a local anaesthetic associated with hyaluronidase or placebo in healthy subjects.

Detailed Description

This double-blind crossover "split-mouth" trial evaluated the cardiovascular effects induced by 3.6 mL of the LA 2% HCl mepivacaine with 1:100,000 epinephrine, concomitantly with 75 TRU/mL hyaluronidase or placebo in inferior alveolar nerve block, for the performance of bilateral and symmetrical third molar surgery in 20 outpatients. Cardiovascular parameters, including systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR), were monitored using oscillometric and photoplethysmographic methods in 10 clinical stages. Electrocardiographic records (ECG) of 12 leads were obtained in four steps. Hyaluronidase injected concomitantly with LA did not induce changes in SBP, DBP and HR compared to placebo. There were no instances of ST segment depression, ST segment elevation, wide QRS complex extrasystoles, or narrow QRS complex extrasystoles.

To date, few studies in dentistry have investigated the effects of local anaesthetic efficacy in hyaluronidase, and even fewer have studied the relation to systemic effects induced by this interaction.

The use of LA injected concomitantly with 75 TRU/mL of hyaluronidase is safe when using this dose and route of administration.

Clinical Relevance: In dentistry, few studies have investigated the effects of hyaluronidase on local anaesthetic efficacy, and even fewer have examined the possible systemic effects induced by this interaction.

Study Timeline

• Study Start: 2007-10
• Primary Completion: 2007-10
• Study Completion: 2011-12
• Status Verified: 2012-10
• Study First Submitted: 2012-10-03
• Study First Submitted QC: 2012-10-30
• Last Update Submitted: 2012-10-31
• Study First Posted: 2012-11-01
• Last Update Posted: 2012-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Patients should present bilateral lower third molars (teeth 38 and 48) for extraction and identical anatomical arrangement;
• Absence of significant clinical morbidities, ASA I (American Society of Anesthesiologists, 1963);
• Aged over 18 years.

Exclusion Criteria

• Women during pregnancy or lactation;
• Smokers;
• History of sensitivity to any drug used in the research;
• Presence or history of cancer or an infectious lesion;
• Individuals who used any medication in the last 15 days (except oral contraceptives);
• Presence of abscess or pericoronitis in the region to be operated;
• Patients who required supplemental anaesthesia upon anaesthetic block of the inferior alveolar nerve (post-randomisation exclusion).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hyaluronidase	Lower Third Molar Extraction	Lower Third Molar Extraction -- 3.6mL 2% Mepivacaine with 1:100,000 epinephrine + Hyaluronidase
Placebo	Lower Third Molar Extraction	Lower Third Molar Extraction -- Anesthetic: 3.6 mL of the LA 2% HCl mepivacaine with 1:100,000 epinephrine + Placebo (0.9% saline)
Placebo	Placebo	Lower Third Molar Extraction -- Anesthetic: 3.6 mL of the LA 2% HCl mepivacaine with 1:100,000 epinephrine + Placebo (0.9% saline)
Hyaluronidase	Hyaluronidase	Lower Third Molar Extraction -- 3.6mL 2% Mepivacaine with 1:100,000 epinephrine + Hyaluronidase

Primary Outcome Measures

Name	Time	Method
Arrhythmia	5min before anaesthesia	Atrial or ventricular arrhythmias: isolated, paired or clustered extrasystoles, tachycardia, bradycardia and fibrillation.

Secondary Outcome Measures

Name	Time	Method
PR segment	5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day	• Duration of the PR segment, in milliseconds.
QRS complex	5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day	• Duration of the QRS complex, in milliseconds.
Change from baseline Heart rate	5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day	• Change from baseline Heart rate (evaluated period - baseline), in beats per minute. Values will be expressed as the absolute difference and the percentage of change.
Corrected QT	5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day	• Duration of the calculated corrected QT segment (QTc) in milliseconds.
Heart rate (absolute values)	5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day	• Heart rate, (absolute values) in beats per minute.

Trial Locations

Locations (1)

Stomatology Department, FOUSP; 🇧🇷 Sao Paulo, Brazil