Ketamine Versus Magnesium Sulfate in the Time and Awakening Quality of General Anesthesia.

Study Overview
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Brief Summary
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The introduction of the laparoscopic technique for cholecystectomy significantly reduced the incidence and intensity of postoperative pain, with improvement in other markers, such as patient satisfaction, and reduction in hospital stay. However, pain in the postoperative period of laparoscopic cholecystectomy is still a concern that challenges modern anesthesiology. Ketamine and magnesium sulfate are two blockers of N-methyl-D-aspartate (NMDA) receptors with the ability to reduce postoperative pain and postoperative opioid consumption. A frequent concern among anesthesiologists is the quality and time of awakening in patients receiving these medications The main objective of this trial is to compare the quality and time of awakening in patients receiving magnesium sulfate or ketamine. The secondary objective is to compare postoperative analgesia during the postoperative hospital stay. Hypothesis: Our hypothesis is that patients have a faster awakening when they receive magnesium sulfate as an analgesic adjunct, when compared to patients who receive ketamine . Design: this is a prospective, controlled, covered and randomly distributed trial.

Detailed Description
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Intervention: the sample of participants will be distributed in 4 groups. The placebo (PG) group will receive 100 ml of saline solution 15 min before anesthetic induction. The ketamine group (KG) will receive 0.3 mg / kg of ketamine in saline (total volume of 100 ml) 15 min before anesthetic induction. The magnesium sulfate group (SG) will receive 40 mg / kg of magnesium sulfate in saline solution (total volume of 100 ml) 15 min before anesthetic induction. The mixed group (MG) will receive 0.15 mg / kg of ketamine + 20 mg / kg of magnesium sulfate in saline solution (total volume of 100 ml) 15 min before anesthetic induction. All participants will be submitted to balanced anesthesia. Anesthetic induction will be started after 5 min of pre-oxygenation, with lidocaine 1.5 mg / kg, fentanyl 3 µg / kg, propofol until clinical hypnosis, cisatracurium 0.1 mg / kg and intubation after adequate neuromuscular relaxation. Maintenance will be with sevoflurane in concentration under clinical demand, repeating boluses of fentanyl 1 µg / kg and cisatracurium 0.03 mg / kg, as needed. Primary Outcomes: time between the end of anesthetic administration and bispectral index (BIS) > 60, and a battery of neuropsychological tests to assess postoperative cognitive dysfunction tested in the Brazilian population 3 h after the end of anesthetic administration. Secondary Outcomes: response to the brief pain inventory questionnaire and opioid consumption in the first 2 postoperative days. Recruitment and timeline : patients will be recruited in the pre-anesthetic evaluation and assessments will be made of covertly in the immediate postoperative period and during the two days after surgery, being registered the pain scores and the consumption of opioids. Sample calculation: the sample of 120 participants was calculated with a 95% confidence index and 80% statistical power. To compensate for losses, 140 individuals will be recruited.

Official Title
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Ketamine Versus Magnesium Sulfate in the Time and Awakening Quality of General Anesthesia. Randomized Clinical Study.

Conditions
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Awakening, Post-Anesthesia Delayed

Intervention / Treatment
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* Other: General anesthesia
* Drug: Ketamine plus general anesthesia
* Drug: Magnesium sulfate plus general anesthesia
* Drug: ketamine plus magnesium sulfate plus general anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients scheduled to undergo laparoscopic cholecystectomy, agreement to voluntarily participate in the trial and sign the free and informed consent form. Exclusion Criteria: Coronary disease, ventricular atrial block II or worse, with renal failure , previous history of brain disease, dementia or other psychiatric diseases, and patients with a body mass index> 35 kg / m² , allergy to any products used in the trial, preoperative use of opioids or corticosteroids.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, controlled, covered and randomly distributed trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>The patients in this group will receive general balanced anesthesia | Other: General anesthesia<br>* Balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane.<br>* Other names: Control group;|
| Experimental: Ketamine group<br>The patients in this group will receive 0.3 mg / kg of ketamine in saline (total volume of 100 ml) 15 min before general balanced anesthetic induction | Drug: Ketamine plus general anesthesia<br>* ketamine 0.3 mg / kg 15 minutes before balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane.<br>* Other names: Ketamine group;|
| Experimental: Magnesium sulfate group<br>The patients in this group will receive 40 mg / kg of magnesium sulfate in saline solution (total volume of 100 ml) 15 min before general balanced anesthetic induction | Drug: Magnesium sulfate plus general anesthesia<br>* Magnesium sulfate 40 mg / kg 15 minutes before balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane.<br>* Other names: Magnesium sulfate group;|
| Experimental: Magnesium / ketamine group<br>The patients in this group will receive 0.15 mg / kg of ketamine + 20 mg / kg of magnesium sulfate in saline solution (total volume of 100 ml) 15 min before general balanced anesthetic induction | Drug: ketamine plus magnesium sulfate plus general anesthesia<br>* Ketamine 0.15 mg/kg plus magnesium sulfate 20 mg/kg 15 minutes before balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane<br>* Other names: Magnesium / ketamine group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time for awakening | Time, after the end of anesthetic administration, to get the bispectral index (BIS) > 60. | Three hours | 
| Awakening quality | Questions related to name, place, time, reason for hospitalization and verbal learning test, consisting of 15 words that the patient will be asked to repeat 20 minutes after hearing them. The wrong answers will be compared among groups. | Three hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain | Verbal pain score 0 (without pain) to 10 (worst imaginable pain), and the effect of pain over humor, ambulation and sleep, each one 0 (without effect) to 10 (worst imaginable effect) | Two days | 
| Postoperative analgesia | Opioid consumption | Two days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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general anesthesia, postoperative awakening, magnesium sulfate, ketamine