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

Awakening, Post-Anesthesia Delayed Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04360473
• Other study ID #: CAAE 28762619.0.0000.5448
• Status: Recruiting
• Phase: N/A
• Start date: March 14, 2022
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: University of Sao Paulo General Hospital
• Contact: sebastião ernesto
• Phone: 12991457764
• Email: sebasernesto[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Awakening, Post-Anesthesia Delayed
• Delayed Emergence from Anesthesia

Intervention

Other:
• General anesthesia
Balanced general anesthesia. Induction with lidocaine, fentanyl, propofol and cisatracurium. Maintenance with sevoflurane.

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.
• 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.
• 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

Locations

Country	Name	City	State
Brazil	Hospital da Beneficência Portuguesa de Santos	Santos	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time for awakening	Time, after the end of anesthetic administration, to get the bispectral index (BIS) > 60.	Three hours
Primary	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	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
Secondary	Postoperative analgesia	Opioid consumption	Two days