Magnesium Sulfate Dose in Obese Patients.
Condition: Magnesium Sulfate; Postoperative Pain; Obesity
MeSH terms: Pain, Postoperative
Study type: Interventional

Summary: 
      Magnesium sulfate has been applied in various situations due to actual or potential benefits
      related to neuroprotection, treatment of eclampsia/pre-eclampsia, arterial hypertension,
      adrenergic reflex under laryngoscopy/intubation and, shivering, nausea and vomiting, among
      others. In anesthesia it has been useful as an analgesic adjuvant; however, the method to
      calculate the dose of magnesium sulfate in obese population is unclear. The objective of this
      project is to compare two methods of dose calculation based either on the real weight or
      corrected ideal weight.
    

Detailed description: 
      Magnesium sulfate has been applied in various situations due to actual or potential benefits
      related to neuroprotection, treatment of eclampsia/pre-eclampsia, arterial hypertension,
      adrenergic reflex under laryngoscopy/intubation and, shivering, nausea and vomiting, among
      others. In anesthesia it has been useful as an analgesic adjuvant; however, the method to
      calculate the dose of magnesium sulfate in obese population is unclear. The objective of this
      project is to compare two methods of dose calculation based either on the real weight or
      corrected ideal weight.

      Main objective: To determine the optimum strategy to safely and effectively obtain the value
      of magnesium concentration in the blood of obese population.

      Secondary objectives: To evaluate postoperative analgesia and the pharmacokinetic profile of
      neuromuscular blocker used in each group.

      Hypothesis: The null hypothesis is that no matter which method we use to calculate the
      magnesium sulfate dosage, the blood magnesium concentration will be the same. The alternative
      hypothesis is that magnesium sulfate dosage based on the patient's actual weight generates
      higher concentrations of magnesium than that required for postoperative analgesia, as
      compared with dosage based on that corrected ideal weight of the patient.

      Trial design: this is a prospective, controlled, randomized and double-blind clinical trial.

      Study setting This study will be conducted at Beneficence Portuguese Society, Santos, an
      academic hospital, in São Paulo, Brazil. A sample of 75 participants will be recruited from a
      population of obese patients scheduled to undergo cholecystectomy or bariatric surgery
      through laparoscopy.

      Interventions In the first phase of the trial, 10 patients with body mass index 20-30 kg/m²
      will be administered magnesium sulphate 40 mg/kg at anesthetic induction. In all patients,
      blood collection will be conducted before administration of magnesium sulfate, and at 15, 30,
      60, 120 and 240 minutes after administration of magnesium sulfate.

      In the second phase of the trial, from among obese patients scheduled to undergo
      cholecystectomy or bariatric surgery through laparoscopy at our institute, 75 patients will
      be invited to participate in the trial. Participants will be assigned to three groups by
      electronic randomization process as follow: Placebo group (PG) without administration of
      magnesium sulfate; real weight group (RWG) administration of magnesium sulfate at 40 mg/kg of
      the patient's actual weight; corrected ideal weight group (CWG) administration of magnesium
      sulphate at 40 mg/kg of patient's corrected ideal weight.

      The corrected ideal weight will be calculated using the following formulas:

      Ideal weight Man = height (cm) - 100 Woman = height (cm) - 105 Corrected ideal weight = Ideal
      weight + (0,4 x difference between the real and ideal weight) The participants will not be
      administered any sedative agent before anesthetic induction. At arrival in the operating
      room, all patients will undergo electrocardiography, noninvasive blood pressure measurement,
      pulse oximetry, monitoring of neuromuscular function, and that of the level of consciousness.
      Venous access and hydration will be achieved according to the anesthesiologist's judgment. At
      the time of puncture of the vein, the first 2-ml blood sample will be collected to establish
      the basal concentration of magnesium in the blood. Within 10 min after collection of the
      blood, dosage will be calculated according to the following chart (Figure 1).

      In all participants, infusion of treatment solution will be performed by a blinded
      investigator, and ketoprofen 100 mg, clonidine 2 µg/kg, cefazolin 2 g, dexamethasone 4 mg,
      ranitidine 50 mg and lidocaine 1,5 mg/kg will be administered simultaneously. At the end of
      infusion participants will undergo pre-oxygenation with 100% O2 for 3 to 5 min, followed by
      propofol through target controlled infusion with initial target of 4 µg/ml according to
      Marsh's pharmacokinetic model, under monitoring for the level of hypnoses. At the time of
      adequate level of hypnoses, revealed by the hypnoses monitor (SedLine® Brain Function
      Monitoring) calibration of the monitor of neuromuscular function (train-of-four - TOF) will
      be performed; subsequently, cisatracurium 0.15 mg/kg will be administered, and
      target-controlled infusion of remifentanil (Minto's pharmacokinetic model) at initial target
      concentration of 5 ng/ml will be conducted. Under hypnoses monitoring, 0.03 mg/kg
      cisatracurium will be administered if TOF ≥ 2 is observed or on surgical demand. Remifentanil
      infusion will be conducted according to the patient's hemodynamics, such that systolic
      pressure is maintained within 30% limits from the baseline value, or maximum value of 130
      mmHg and minimum value of 90 mmHg are achieved. During the last 20 minutes' period of
      surgery, cisatracurium will be withheld, when possible. At the end of surgery, at TOF > 2,
      atropine 20 µg/kg and neostigmine 40 µg/kg will be administered.

      Before extubation, the patients in both groups will be administered morphine 0,05 mg/kg and
      dipyrone 30 mg/kg. Five minutes after extubation and after each 30 minutes' interval, repeat
      dose of morphine will be administered at pain-score of > 3 (0 to 10) of the patient.
    

Intervention name(s): Magnesium sulfate through real weight group; Placebo group; Magnesium sulfate through ideal corrected weight group
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Magnesium sulfate dose 40 mg/kg of actual patient's weight; Saline solution (instead of magnesium sulfate, as in the other groups); Magnesium sulfate dose 40 mg/kg of ideal corrected patient's weight
Other intervention name(s): Real weight group; Ideal weight group
Intervention MeSH terms: Magnesium Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective, double-blind, randomized clinical trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment