Clinical trial NCT01719978: Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics
Official title: Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics: a Double-blind "Split-mouth" Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiac Arrhythmias
Keywords: Local Anaesthetics
Mepivacaine
hyaluronoglucosaminidase
Hemodynamic
Electrocardiography and Dentistry.
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
First posted: 2012-11-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Arrhythmia
timeFrame: 5min before anaesthesia
Secondary outcomes:
measure: PR segment
timeFrame: 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
measure: QRS complex
timeFrame: 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
measure: Change from baseline Heart rate
timeFrame: 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
measure: Corrected QT
timeFrame: 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
measure: Heart rate (absolute values)
timeFrame: 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
Other outcomes:
measure: Systolic Pressure (absolute values)
timeFrame: 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
measure: Diastolic Pressure (absolute values)
timeFrame: 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
measure: Mean Blood Pressure (absolute values)
timeFrame: 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
measure: Change from baseline Diastolic Pressure
timeFrame: 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
measure: Change from baseline Systolic Pressure
timeFrame: 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
measure: Change from baseline Mean Arterial Blood Pressure
timeFrame: 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
Locations:
city: Sao Paulo
country: Brazil
facility: Stomatology Department, FOUSP
Study officials:
affiliation: FMUSP
name: Gustavo F Prado, PhD
role: STUDY_CHAIR
affiliation: FOUSP
name: Maria A Borsatti, PhD
role: STUDY_DIRECTOR
affiliation: FOUSP
name: Rodney G Rocha, PhD
role: STUDY_DIRECTOR
affiliation: FOUSP
name: Helena R Tornelli, MD, S
role: STUDY_CHAIR
affiliation: FOUSP
name: Renata MS Prado, MS, S
role: STUDY_CHAIR
References: