Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics

Cardiac Arrhythmias Clinical Trial

Official title:

Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics: a Double-blind "Split-mouth" Controlled Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01719978
• Other study ID #: MTornelli
• Status: Completed
• Phase: Phase 4
• First received: October 3, 2012
• Last updated: October 31, 2012
• Start date: October 2007
• Est. completion date: December 2011

Study information

• Verified date: October 2012
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2011
• Est. primary completion date: October 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Cardiac Arrhythmias

Intervention

Drug:
• 3.6mL 2% Mepivacaine with 1:100,000 epinephrine
Local anesthetic with vasoconstrictor

Procedure:
• Lower Third Molar Extraction
Lower Third Molar Extraction with LA + hyaluronidase (or placebo)

Drug:
• Hyaluronidase
75RTU Hyaluronidase administration concomitant to the local anesthetic
• Placebo
1mL 0.9% saline administration concomitant to the local anesthetic

Locations

Country	Name	City	State
Brazil	Stomatology Department, FOUSP	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Mauricio Jose Tornelli	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Systolic Pressure (absolute values)	Systolic Blood Pressure (absolute values), in mmHg.	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	Yes
Other	Diastolic Pressure (absolute values)	Diastolic Blood Pressure, in mmHg.	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	Yes
Other	Mean Blood Pressure (absolute values)	Mean Blood Pressure, in mmHg.	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	Yes
Other	Change from baseline Diastolic Pressure	• Change from baseline Diastolic Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.	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	Yes
Other	Change from baseline Systolic Pressure	• Change from baseline Systolic Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.	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	Yes
Other	Change from baseline Mean Arterial Blood Pressure	• Change from baseline Mean Arterial Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.	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	Yes
Primary	Arrhythmia	Atrial or ventricular arrhythmias: isolated, paired or clustered extrasystoles, tachycardia, bradycardia and fibrillation.	5min before anaesthesia	Yes
Secondary	PR segment	• Duration of the PR segment, in milliseconds.	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	Yes
Secondary	QRS complex	• Duration of the QRS complex, in milliseconds.	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	Yes
Secondary	Change from baseline Heart rate	• 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.	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	Yes
Secondary	Corrected QT	• Duration of the calculated corrected QT segment (QTc) in milliseconds.	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	Yes
Secondary	Heart rate (absolute values)	• Heart rate, (absolute values) in beats per minute.	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	Yes