Analgesic Effect of Intraoperative Esmolol in Mastectomies (Esmobreast)

April 3, 2017 updated by: Fabricio Tavares Mendonca, Hospital de Base

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • DF
      • Brasilia, DF, Brazil, 70680250
        • Hospital de Base do Distrito Federal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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);

Exclusion Criteria:

  • 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
  • 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;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo group
Patients in placebo group will receive general balanced inhaled anesthesia with sevoflurane and remifentanil and a saline 0,9% infusion pump.
Patients will receive regular general anesthesia
Other Names:
  • Saline
Active Comparator: Esmolol group
Patients 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
Patients will receive regular general anesthesia plus esmolol infusion
Other Names:
  • Esmolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Scores on the Visual Analogue Scale
Time Frame: Within the first 24 hours after surgery
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
Within the first 24 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Scores on the Verbal Rating Scale
Time Frame: Within the first 24 hours after surgery
Verbal Rating Scale (VRS), consisting of a list of phrases (no pain, mild pain, moderate pain, intense pain, maximum pain)
Within the first 24 hours after surgery
Analgesics consumption in post-operative
Time Frame: Within the first 24 hours after surgery
Qualification of pain assessed by the amount of analgesics required postoperatively and the time to request them
Within the first 24 hours after surgery
Analgesic consumption during surgery
Time Frame: During the surgery
The amount of intravenous and inhaled anesthetics consumed during surgery
During the surgery
Number of participants with adverse events as a measure of safety and tolerability
Time Frame: During the surgery
Intraoperative hemodynamic stability analysis through the incidence of tachycardia, hypertension, bradycardia, hypotension and consumed vasopressors
During the surgery
Number of participants with adverse events as a measure of safety and tolerability
Time Frame: Within the first 24 hours after surgery
Incidence of adverse effects such as time of awakening, nausea, vomiting, pruritus, urinary retention, drowsiness
Within the first 24 hours after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

February 1, 2017

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

June 5, 2015

First Submitted That Met QC Criteria

June 8, 2015

First Posted (Estimate)

June 9, 2015

Study Record Updates

Last Update Posted (Actual)

April 5, 2017

Last Update Submitted That Met QC Criteria

April 3, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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