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

• ClinicalTrials.gov Identifier: NCT04360473
• Recruitment Status: Recruiting
• First Posted: April 24, 2020
• Last Update Posted: March 29, 2022
• Sponsor: University of Sao Paulo General Hospital
• Information provided by (Responsible Party): Joaquim Edson Vieira, University of Sao Paulo General Hospital

Tracking Information

• First Submitted Date: April 18, 2020
• First Posted Date: April 24, 2020
• Last Update Posted Date: March 29, 2022
• Actual Study Start Date: March 14, 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2020)

• Time for awakening [ Time Frame: Three hours ]
  Time, after the end of anesthetic administration, to get the bispectral index (BIS) > 60.
• Awakening quality [ Time Frame: Three hours ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 21, 2020)

• Postoperative pain [ Time Frame: Two days ]
  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)
• Postoperative analgesia [ Time Frame: Two days ]
  Opioid consumption

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.

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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a prospective, controlled, covered and randomly distributed trial

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The person responsible for generating the sequence will use the result of the lottery to number the opaque envelopes and place the intervention corresponding to the group to which that lottery number belongs. This professional will not administer anesthesia to the patients in the study and will not participate in the collection or evaluation of the studied variables.

The envelopes will be opened by professionals who will prepare the corresponding solution, keeping this information covered for the other members of the team and for the patients.

The groups will be covered up for patients and for professionals who carry out the assessments.

Primary Purpose: Treatment

• Condition: Awakening, Post-Anesthesia Delayed

Intervention

• Other: General anesthesia
  Balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane.
  Other Name: Control group
• Drug: Ketamine plus general anesthesia
  ketamine 0.3 mg / kg 15 minutes before balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane.
  Other Name: Ketamine group
• Drug: Magnesium sulfate plus general anesthesia
  Magnesium sulfate 40 mg / kg 15 minutes before balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane.
  Other Name: Magnesium sulfate group
• Drug: ketamine plus magnesium sulfate plus general anesthesia
  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
  Other Name: Magnesium / ketamine group

Study Arms

• Active Comparator: Control group
  The patients in this group will receive general balanced anesthesia
  Intervention: Other: General anesthesia
• Experimental: Ketamine group
  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
  Intervention: Drug: Ketamine plus general anesthesia
• Experimental: Magnesium sulfate group
  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
  Intervention: Drug: Magnesium sulfate plus general anesthesia
• Experimental: Magnesium / ketamine group
  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
  Intervention: Drug: ketamine plus magnesium sulfate plus general anesthesia

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 21, 2020): 140
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: sebastião ernesto; 12991457764; sebasernesto@gmail.com

• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT04360473
• Other Study ID Numbers: CAAE 28762619.0.0000.5448
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Joaquim Edson Vieira, University of Sao Paulo General Hospital
• Study Sponsor: University of Sao Paulo General Hospital
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joaquim Vieira; University of Sao Paulo School of Medicine

• PRS Account: University of Sao Paulo General Hospital
• Verification Date: March 2022