Magnesium Sulfate Versus Dexmedetomidine on Anesthesia Awakening.
Condition: Cholecystectomy
Study type: Interventional
Phase: Phase 3

Summary: 
      Magnesium sulfate (MS) and dexmedetomidine have already demonstrated the ability to reduce
      intra and postoperative consumption of anesthetics and analgesics, among others advantages,
      such as blood pressure control and intraoperative bleeding. The MS has also been shown to be
      useful in pre-eclampsia and eclampsia control, pulmonary hypertension, asthma, cardiac
      arrhythmias and pheochromocytoma). Despite these advantages in the use of these important
      adjuncts, there is a concern about the quality and awakening time of the patients who use
      them. The purpose of this trial is to compare the time and quality of awakening in patients
      submitted to general anesthesia and receiving MS or dexmedetomidine as adjuncts in the
      intraoperative analgesia.

      The main objective of this trial is to compare the quality and the awakening time in patients
      receiving MS or dexmedetomidine. The secondary objective is the comparison of postoperative
      analgesia in the postoperative hospitalization period. Hypothesis: Our hypothesis is that
      patients present a faster awakening when receive MS as an analgesic adjunct, when compared to
      patients who receive dexmedetomidine. Drawing: this is a prospective, controlled, covert
      trial with random distribution for noninferiority trialing.
    

Detailed description: 
      INTRODUCTION Magnesium sulfate (MS) and dexmedetomidine have already demonstrated the ability
      to reduce intra and postoperative consumption of anesthetics and analgesics, among others
      advantages, such as blood pressure control and intraoperative bleeding8,9. The MS has also
      been shown to be useful in pre-eclampsia and eclampsia control, pulmonary hypertension,
      asthma, cardiac arrhythmias and pheochromocytoma). Despite these advantages in the use of
      these important adjuncts, there is a concern about the quality and awakening time of the
      patients who use them. The purpose of this trial is to compare the time and quality of
      awakening in patients submitted to general anesthesia and receiving MS or dexmedetomidine as
      adjuncts in the intraoperative analgesia.

      The main objective of this trial is to compare the quality and the awakening time in patients
      receiving MS or dexmedetomidine. The secondary objective is the comparison of postoperative
      analgesia in the postoperative hospitalization period. Our hypothesis is that patients
      present a faster awakening when receive MS an analgesic adjunct, when compared to patients
      who receive dexmedetomidine.

      Drawing: this is a prospective, controlled, covert trial with random distribution for
      noninferiority trialing.

      Key words: general anesthesia, long awakening from anesthesia. METHODS Participants and
      endpoints Scenario: The study will be carried out at "Hospital da Sociedade Portuguesa de
      Beneficência de Santos - Angiocorpore" (Portuguese Charity Society Hospital). Eligibility:
      Patients scheduled for video laparoscopic cholecystectomy, between 18 and 70 years old,
      physical status I or II in the American Society of Anesthesiology classification, who have no
      allergy or contraindication to the study protocol substances and who voluntarily agree to
      participate in the trial and sign the informed consent form (TCLE), will be invited to
      participate in the study.

      Coronary disease patients, patients with heart block > atrioventricular block > I, patients
      with renal failure, those with brain disease past history, dementia or other psychiatric
      diseases, and patients with body mass index > 35 kg/m², will be excluded. Also excluded
      patients with Portuguese language limitations and in preoperative use of opioid or
      corticosteroids.

      Intervention: the sample of participants will be distributed in 3 groups. The placebo group
      (GP) will receive 100 ml of saline solution (SL) in infusion pump (BI) starting 15 min before
      anesthesia with flow of 0.25 ml/kg/h. The dexmedetomidine group (GD) will receive 100 ml of
      SL with 200 µg of dexmedetomidine in BI, starting 15 min before anesthesia with flow of 0.25
      ml/kg/h. The magnesium sulfate group (GM) will receive 80 ml of MS + 20 ml of SL in infusion
      pump starting 15 min before anesthesia induction with flow of 0.25 ml/kg/h. With this
      infusion flow, patients of GD will receive dexmedetomidine at a dose of 0.5 µg/kg/h and
      patients of GM will receive MS at a dose of 20 mg/kg/h. All participants will be submitted to
      balanced anesthesia.

      Anesthetic induction will be initiated after 5 min of pre-oxygenation, with lidocaine 1.5
      mg/kg, fentanyl 3 µg/kg, propofol up to clinical hypnosis, cisatracurium 0.1 mg/kg and
      intubation after adequate neuromuscular relaxation. Maintenance will be with sevoflurane at a
      concentration under clinical demand, repeating bolus of fentanyl 1µg/kg and cisatracurium
      0.03 mg/kg as needed.

      Primary endpoints: time between the end of anesthetic administration and bispectral index >
      60, and a battery of neuropsychological trials for evaluation of postoperative cognitive
      dysfunction tested in the Brazilian population 3 h after the end of anesthetics
      administration.

      . Secondary endpoints: response to the questionnaire of the brief pain inventory and opioid
      consumption in the first 2 days of postoperative. Recruitment: patients will be recruited in
      the pre-anesthetic evaluation and the evaluations will be done in a covert way in the
      immediate postoperative period and during the two postoperative days, being recorded the pain
      scores and consumption of opioids.

      Sample calculation: the sample of 73 participants was calculated for a 95% confidence index
      and a 90% statistical power. For compensation for losses, 90 individuals will be recruited
      distributed in 3 groups.

      Recruitment and allocation Distribution in groups: through electronic drawing on the website
      www.random.org and preparation of brown envelopes that will be numbered and will contain
      inside a card with the name of the group to which that number corresponds, in addition to the
      intervention concerning the group to which it belongs. The draw and preparation of the
      envelopes will be conducted by a professional who will not participate in other stages of the
      study.

      Masking: participants, providers and evaluators will be blinded to group each patient belongs
      to. The randomization and allocation will be performed by professional not participating in
      any other step of the trial.

      Data collection and management Collection: the time between the end of anesthetic
      administration and bispectral index > 60 monitoring will be recorded; cognitive evaluation
      will be done at recruitment and 3 h after the end of the anesthesia; the brief pain inventory
      questionnaire will be filled in at recruitment and 3 h after the end of the anesthesia;
      during hospitalization and in the first 2 days of postoperative the opioid consumption will
      be registered.

      Data management: the data will be organized in MS Excel spreadsheet, in its MS-Office 2013
      version. The results will be obtained through the Statistical Package for Social Sciences
      (SPSS) in its version 23.0.

      Statistical analysis: continuous variables will be evaluated through Student's t trial. The
      normality check will be evaluated by Kolmogorov-Smirnov trial or Shapiro-Wilk trial. The
      comparison of parametric data will be done by Student's t trial or Z trial. The nominal
      variables will be evaluated by the Chi-square trial. The comparison of nominal variables for
      independent samples will be made by the Chi-square trial or Fisher's Exact trial. The
      comparison of ordinal or quantitative variables without normal distribution for independent
      samples will be done by the Mann-Whitney trial. The correlation between variables will be
      evaluated by Pearson's trial for or Spearman, as indicated.

      Patient follow-up The compared substances are already widely used in anesthesia and present a
      very favorable risk/benefit ratio, with no significant incidence of intercurrence related to
      them being noted. The selection of patients for the study also makes their use safe. To make
      the benefit of its use uniform among the groups, patients with pain scores > 3 (pain verbal
      score 0 to 10) will receive 2 mg of morphine at 15-minute intervals, until the pain intensity
      is < 3.

      Participants will receive a prescription for home use of dipyrone 1g every 6 hours and
      association of codeine (30 mg) with paracetamol (500 mg) in case of pain > 3. RESEARCH ETHICS
      This project was submitted to the evaluation of the Research Ethics Committee (CEP/CONEP) in
      the Brazil Platform and to the Ethics Committee of participating institution. After their
      approval, it is being registered at clinicaltrials.org. Only after these steps the data
      collection will started.

      The recruited individuals will only participate in the study after signing the consent form.

      Participants' personal information will be kept confidential, and only the authors will have
      access to them before, during and after the trial. The authors declare that they have no
      conflict of interest.
    

Intervention name(s): Dexmedetomidine; Sham treatment; Magnesium Sulfate
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Patients will start receiving dexmedetomidine 15 minutes before general anesthetic induction.; Patients will start receiving saline solution infusion 15 minutes before general anesthetic induction.; Patient will start receiving magnesium infusion (20 mg/kg/h) 15 minutes before general anesthetic induction.
Other intervention name(s): Dexmedetomidine and general anesthesia; Saline solution and general anesthesia; Magnesium sulfate and general anesthesia
Intervention MeSH terms: Magnesium Sulfate; Dexmedetomidine; Anesthetics
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a prospective, controlled, blinded trial with random distribution.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment