Clinical trial NCT04360473: Ketamine Versus Magnesium Sulfate in the Time and Awakening Quality of General Anesthesia.
Official title: Ketamine Versus Magnesium Sulfate in the Time and Awakening Quality of General Anesthesia. Randomized Clinical Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Awakening, Post-Anesthesia Delayed
Keywords: postoperative awakening
general anesthesia
magnesium sulfate
ketamine
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, controlled, covered and randomly distributed trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time for awakening
timeFrame: Three hours
measure: Awakening quality
timeFrame: Three hours
Secondary outcomes:
measure: Postoperative pain
timeFrame: Two days
measure: Postoperative analgesia
timeFrame: Two days
Other outcomes:
Locations:
city: Santos
country: Brazil
facility: Hospital da Beneficência Portuguesa de Santos
state: São Paulo
Study officials:
affiliation: University of Sao Paulo School of Medicine
name: Joaquim Vieira
role: PRINCIPAL_INVESTIGATOR
References:
citation: REFERENCES 1. Hendolin HI, Pääkkönen ME, Alhava EM, Tarvainen R, Kemppinen T, Lahtinen. Laparoscopic or open cholecystectomy: a prospective randomized trial to compare postoperative pain, pulmonary function, and stress response. Eur J Surg. 2000; 166: 394-9. 2. Attwood SEA, Hill ADK, Mealy K, Stephens RB. A prospective comparison of laparoscopic versus open cholecystectomy. Annlas of the Royal College of Surgeons of England. 1992; 74: 397-400. 3. Keus F, by Jong J, Gooszen HG, Laarhoven CJHM. Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. Cochrane Database of Systematic Reviews. 2006, Issue 4. Art. No.: CD006231. 4. Barazanchi AWH, MacFater WS, Rahiri JL, Tutone S, Hill AG, Joshi GP. Evidence-based management of pain after laparoscopic cholecystectomy: a PROSPECT review update. Br J Anaesth. 2018; 121: 787-803. 5. Bisgaard T, Klarskov B, Rosenberg J, Kehlet H. Characteristics and prediction of early pain after laparoscopic cholecystectomy. Pain. 2001 ; 90: 261-9. 6. Ye Fan, Wu Y, Zhou C. Effect of intravenous ketamine for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. Meta-analysis. Medicine. 2017; 96: 51 7. Launo C, Bassi C, Spagnolo L, Badano S, Ricci C, Lizzi A, et al. Preemptive ketamine during general anesthesia for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. Minerva Anestesiol. 2004; 70: 727-38. 8. Hang LH, Shao DH, Gu YP. The ED50 and ED95 of ketamine for prevention of postoperative hyperalgesia after remifentanil-based anesthesia in patients undergoing laparoscopic cholecystectomy. Swiss Med Wkly. 2011; 141: w13195 . 9. Minds O, Harlak A, Yigit T, Balkan A, Balkan M, Cosar A, et al. Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008; 52: 1353-9. 10. Chen C, Tao R. The impact of magnesium sulfate on pain control after laparoscopic cholecystectomy: a meta-analysis of randomized controlled studies. Surg Laparosc Endosc Percutan. 2018; 28: 349-53. 11. Valentin LSS, Pietrobon R, Junior WA, et al. Definition and application of a battery of neuropsychological tests to assess postoperative cognitive dysfunction. Einstein. 2015; 13: 20-6.