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Completed

NCT Number: NCT01719978

Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Stomatology Department, FOUSP

São Paulo, 05508-000, Brazil

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

3.6mL 2% Mepivacaine with 1:100,000 epinephrine

Drug

Local anesthetic with vasoconstrictor

Other names: Mepivacaine with epinephrine

Lower Third Molar Extraction

Procedure

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

Other names: Molar surgery

Hyaluronidase

Drug

75RTU Hyaluronidase administration concomitant to the local anesthetic

Placebo

Drug

1mL 0.9% saline administration concomitant to the local anesthetic

Other names: Saline, 0.9% NaCl

Primary outcomes

  1. Arrhythmia

    Time frame: 5min before anaesthesia

    Atrial or ventricular arrhythmias: isolated, paired or clustered extrasystoles, tachycardia, bradycardia and fibrillation.

Secondary outcomes

  1. PR segment

    Time frame: 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.
  2. QRS complex

    Time frame: 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.
  3. Change from baseline Heart rate

    Time frame: 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.
  4. Corrected QT

    Time frame: 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.
  5. Heart rate (absolute values)

    Time frame: 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.

Other outcomes

  1. Systolic Pressure (absolute values)

    Time frame: 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

    Systolic Blood Pressure (absolute values), in mmHg.

  2. Diastolic Pressure (absolute values)

    Time frame: 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

    Diastolic Blood Pressure, in mmHg.

  3. Mean Blood Pressure (absolute values)

    Time frame: 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

    Mean Blood Pressure, in mmHg.

  4. Change from baseline Diastolic Pressure

    Time frame: 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 Diastolic Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.
  5. Change from baseline Systolic Pressure

    Time frame: 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 Systolic Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.
  6. Change from baseline Mean Arterial Blood Pressure

    Time frame: 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 Mean Arterial Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.

Sponsors and collaborators

Lead sponsor

Mauricio Jose Tornelli

Other

Collaborators

  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Registry information

Official study title

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

Important dates

Study start
2007
Primary completion
2007
Study completion
2011
First posted
Nov 1, 2012
Registry last updated
Nov 2, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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