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Postoperative PainPhase 4EsmobreastNCT02466542

Analgesic Effect of Intraoperative Esmolol in Mastectomies

A Phase 4 study testing Esmolol group in people with Postoperative Pain, run by Hospital de Base at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study aims to compare the quality of perioperative analgesia of esmolol in patients undergoing mastectomy. Read more about this study

Who is it for?
Ages 18 to 75 years, women only
Conditions the study is for
Postoperative Pain
What is being tested?
Esmolol group
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteBrazil
Study dates
Jun 2015to Feb 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female patients, aged 18 to 75 years, electively scheduled to perform mastectomy in the Base Hospital of the Federal District;
  • Physical State 1 or 2 the American Society of Anesthesiology (ASA);

Who cannot join

  • Patients under the age of 18 years and above 75 years;
  • Patients with unstable angina
  • Patient with poorly controlled asthma
  • Substance abuse
  • Sinus bradycardia
  • Heart failure, greater than first degree atrioventricular block
Show all 15Show fewer
  • Pregnant women
  • Patients with allergy to dipyrone, morphine;
  • Patients with chronic pain;
  • Patients with severe hepatic disease;
  • Patients with severe kidney disease;
  • Patients with neurological diseases;
  • Included patients in other clinical studies currently or in the past three months under general anesthesia;
  • Patients who refuse to participate in the study;
  • Any other condition that, in the opinion of the investigator, may pose a risk to the patient or interfere with the study objectives;

Trial locations and contacts

1 site in 1 country.

Brazil1 site
  • Hospital de Base do Distrito Federal

    Brasília, Federal District, 70680250

Other trials in Brazil

About this study

Official title: Analgesic Effect of Intraoperative Esmolol in Mastectomies: Single Center, Prospective, Double-blind, Randomized and Placebo Controlled Study

This study aims to compare the quality of perioperative analgesia of esmolol in patients undergoing mastectomy.

Read the detailed description

Controlled hypotension is an anesthetic-surgical approach that matches the reversible and deliberate reduction in blood pressure during surgery period which aims to achieve values below 50% of normal values or mean arterial pressure (MAP) from 50 to 65 mmHg.

This technique is especially beneficial in patients undergoing procedures requiring control of bleeding for proper surgical field. The method provides a better view of anatomical structures, reduced surgical time and a significant decrease in the need for blood transfusions, with the added benefit of preventing possible complications from it.

Several drugs have been used in this scenario, as halogenated, opioids, alpha-2-agonists and beta-blockers, among which the esmolol emerges as effective and promising drug.

Esmolol is a selective beta-blocker whose action inhibits preferably the beta type 1 receptors with decreased heart rate (HR) and cardiac inotropic and consequent decrease in consumption of myocardial oxygen. Its half-life of distribution is approximately 2 minutes, the elimination half-life of 9 minutes with 55% protein bound. The duration is short due to rapid metabolism by hydrolysis by esterases in plasma and results in an inactive metabolite with negligible amounts of methanol. It has low solubility, which limits their passage through the blood-brain and placental barrier. Thanks to these features, the esmolol constitutes the most appropriate beta-blocker for intravenous use under continuous infusion.

The use of a selective beta-blocking agent continuously infused intraoperative period as well as promoting adequate blood pressure control in the controlled hypotension, it has additional advantages over other anesthetic agents, such as cardioprotection obtained by suppressing the cardiovascular response to catecholamines released during stress surgical and sympathetic stimulation resulting from laryngoscopy and tracheal intubation. The suppression of cardiovascular adrenergic response allows better coronary perfusion with proven benefits in reducing the incidence of perioperative myocardial ischemia and influence on mortality and morbidity of patients, especially coronary and high risk for ischemic phenomena. There are also several studies that demonstrate the importance of esmolol in the control and prevention of sympathetic response during extubation, better hemodynamics during induction, maintenance and emergence from anesthesia, fewer complications, lower incidence of perioperative nausea, time decreased from room to stay anesthetic recovery and, due to reduced cardiac work, action prolongation of neuromuscular blockers and opioids, saving their use. There are still ongoing studies with important indications that there is potentiation of analgesia and the hypnotic component of anesthesia with the use of esmolol.

Opioid analgesics are commonly used in clinical practice for the treatment of perioperative pain. However, many side effects are associated with its use, such as respiratory depression, nausea, vomiting, drowsiness, itching, urinary retention, constipation, hyperalgesia and impaired immune function. Therefore, alternative techniques and drugs have been used to replace their use. In recent years, the use of adjuvant drugs is becoming more popular in perioperative medicine and anesthesia, as NMDA inhibitors, local anesthetics intravenous, agonists alpha2 and beta-blockers. Some authors is likely pointing analgesic effect of intraoperative infusion of esmolol.

In this context, esmolol emerges as a drug insurance and significant effects, with impact on the quality of the anesthetic technique and the use of which should be further studied and expanded.

The patients underwent a prospective, randomized, double blind, and placebo controlled study in which the examiners responsible for intra and post-operative will not know which group they were randomly allocated: C group (n = 30) and E group (n = 30).

Both groups will receive general inhaled balanced anesthesia with sevoflurane and remifentanil.

Rapid infusion of 0.9% saline 500 ml, in both groups. In the E group is added to this solution the loading dose of esmolol with 500 mcg/kg and in group C will only be infused saline 0.9% . One infusion pump containing the result of randomization: Esmolol 100 mcg/kg/min (E group) and saline (C group).

In the clinical record, the following information will be emphasized: Blood pressure and heart rate intraoperative, perioperative side effects, quantify pain by Visual Analogue Scale (VAS) (ranging from 0 to 10 cm, zero being found when the patient is no pain and ten, with maximum or unbearable pain), Verbal Rating Scale (VRS), consisting of a list of phrases (no pain, mild pain, moderate pain, intense pain, maximum pain) and qualification of pain assessed by the amount of analgesics required postoperatively and the time to request them.

The results were analyzed statistically with the Statistical Package for Social Sciences (SPSS) version 22 (SPSS Inc., Chicago, IL, EUA) using parametric and nonparametric tests, depending on the nature of the variables studied. Data were tested for normality using the Shapiro-Wilk test. Measures of central tendency (means) and dispersion (standard deviation) were used. The level of significance was set at < 0.05. The following tests were used: Mann-Whitney test for age, duration of anesthesia and surgery, time to first analgesic supplementation, total amount of analgesics, pain intensity; Student t-test for weight and height.

Being tested
Placebo group, Esmolol group
Keywords
Esmolol, Pain, Anesthesia, Analgesia
Medical subject headings
Pain, Postoperative, Pain, Agnosia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Placebo groupDrug

    Also called Saline

    Patients will receive regular general anesthesia

  • Esmolol groupDrug

    Also called Esmolol

    Patients will receive regular general anesthesia plus esmolol infusion

Study groups in NCT02466542
Study groupRoleWhat they receive
Placebo groupPlacebo comparatorPatients in placebo group will receive general balanced inhaled anesthesia with sevoflurane and remifentanil and a saline 0,9% infusion pump.
Receives: Drug: Placebo group
Esmolol groupActive comparatorPatients in esmolol group will receive general balanced inhaled anesthesia with sevoflurane and remifentanil and a bolus infection of esmolol 500 mgc/kg followed by a continuous infusion of esmolol 100 mcg/kg/min
Receives: Drug: Esmolol group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pain Scores on the Visual Analogue Scale

    Quantify pain by Visual Analogue Scale (VAS, ranging from 0 to 10 cm, zero being found when the patient is no pain and ten, with maximum or un bearable pain

    Measured: Within the first 24 hours after surgery

Secondary outcomes (5)
  1. Pain Scores on the Verbal Rating Scale

    Verbal Rating Scale (VRS), consisting of a list of phrases (no pain, mild pain, moderate pain, intense pain, maximum pain)

    Measured: Within the first 24 hours after surgery

  2. Analgesics consumption in post-operative

    Qualification of pain assessed by the amount of analgesics required postoperatively and the time to request them

    Measured: Within the first 24 hours after surgery

  3. Analgesic consumption during surgery

    The amount of intravenous and inhaled anesthetics consumed during surgery

    Measured: During the surgery

  4. Number of participants with adverse events as a measure of safety and tolerability

    Intraoperative hemodynamic stability analysis through the incidence of tachycardia, hypertension, bradycardia, hypotension and consumed vasopressors

    Measured: During the surgery

  5. Number of participants with adverse events as a measure of safety and tolerability

    Incidence of adverse effects such as time of awakening, nausea, vomiting, pruritus, urinary retention, drowsiness

    Measured: Within the first 24 hours after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2015 (estimated)
  2. Study startJun 2015
  3. Primary completionFeb 2017
  4. Study completionFeb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02466542
Sponsor's protocol ID
HBase
Acronym
Esmobreast
Status last verified
Apr 2017
First submitted
5 Jun 2015
Last updated
5 Apr 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Celebi N, Cizmeci EA, Canbay O. [Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial]. Rev Bras Anestesiol. 2014 Sep-Oct;64(5):343-9. doi: 10.1016/j.bjan.2013.10.013. Epub 2014 Jun 21. Portuguese.

    PubMed 25168439
  • Kim Y, Hwang W, Cho ML, Her YM, Ahn S, Lee J. The effects of intraoperative esmolol administration on perioperative inflammatory responses in patients undergoing laparoscopic gastrectomy: a dose-response study. Surg Innov. 2015 Apr;22(2):177-82. doi: 10.1177/1553350614532534. Epub 2014 May 6.

    PubMed 24803523
  • Mendonca FT, Volpe Junior JF, Tramontini AJ, DE Carvalho LS, Sposito AC. Intraoperative infusion of esmolol reduces the incidence and intensity of post-mastectomy pain syndrome. Minerva Anestesiol. 2022 May;88(5):414-415. doi: 10.23736/S0375-9393.21.16152-8. Epub 2021 Oct 12. No abstract available.

    PubMed 34636226
  • Mendonca FT, Tramontini AJ, Miake HI, Seixas LF, de Carvalho LSF, Sposito AC. Intra-operative esmolol and pain following mastectomy: A randomised clinical trial. Eur J Anaesthesiol. 2021 Jul 1;38(7):735-743. doi: 10.1097/EJA.0000000000001512.

    PubMed 33831899

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Esmolol group in people with Postoperative Pain, run by Hospital de Base at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pain Scores on the Visual Analogue Scale (time frame: Within the first 24 hours after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02466542, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2017.

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