Analgesic Effect of Intraoperative Esmolol in Mastectomies
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

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

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.
    

Intervention name(s): Placebo group; Esmolol group
Intervention type(s): Drug; Drug
Intervention description(s): Patients will receive regular general anesthesia; Patients will receive regular general anesthesia plus esmolol infusion
Other intervention name(s): Saline; Esmolol
Intervention MeSH terms: Esmolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Esmolol; Pain; Anesthesia; Analgesia