Comparison of BIS Index Variations: Bolus Versus Infusion Ketamine, and Impact on the Anesthesia Gas Consumption

NCT ID: NCT03781635

Last Updated: 2021-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-25
• Study Completion Date: 2019-09-30

Brief Summary

The aim of the present study is to show that i.v. ketamine boluses might lead to significant and clinically relevant BIS index increase that might lead to an increase in anesthesia dosing (halogenous gas) when compared to an i.v. continuous infusion of ketamine without any bolus.

Detailed Description

Hypothesis: The investigators hypothesize that BIS will not vary when ketamine is given as an i.v. infusion whereas BIS index will significantly vary when ketamine is given as intraoperative repeated bolus on an hourly basis. As a consequence, the bolus group might have a higher consumption of halogenous gases to keep BIS within normal values during anesthesia.

Background: ketamine is a pure NMDA-receptor antagonist widely used in anesthesia for its anesthetic and analgesic properties. However, boluses of intravenous ketamine have been reported to increase BIS values. The present study is the first to compare ketamine effect on BIS values when given as an infusion versus repeated boluses.

Objectives: primary objective: to measure the changes in BIS index values (delta BIS) after each bolus of i.v. ketamine 0.25mg.kg-1 given during anesthesia for surgeries lasting more than 3hs, and to demonstrate a significant increase of this BIS index whereas no significant increase is expected when i.v. ketamine is given as a continuous infusion intraoperatively. Secondary objectives: to measure the changes of BIS index values area under the curve when an infusion of i.v. ketamine 0.25mg.kg-1.h-1 is administered to the patient instead of boluses; to evaluate the time in minutes for the BIS index values to return within +/-10% of the pre-bolus values of this BIS index; to evaluate the time in seconds at which the peak of BIS will occur after ketamine bolus; to evaluate the consumption of halogenous gases during the entire surgery and for each hour of anesthesia (T0 = incision = time for first bolus of ketamine or start of ketamine infusion); to evaluate hemodynamic data (all the data from the ventilator and the monitor are recorded and exported per second) in both groups and see if the infusion group shows less hypotension events needing treatment with i.v. phenylephrine to stay within +/-20% of the mean blood pressure baseline; to evaluate the time for awakening, time for extubation, time spent in post-anesthesia care unit (PACU), delirium and cognitive functions in PACU (CAMshort assessment and MOCA).

Methods: REB from CR-HMR will be obtained. 50 patients undergoing elective general, urological, gynecological surgeries will be explained the study at the pre-anesthesia consultation and then fully consented the day of the surgery. Anesthesia protocol will be fully standardized in both the groups. BIS monitoring will be installed before induction of general anesthesia as well as the standard anesthesia monitoring. Randomization into group infusion versus boluses of ketamine will be done prior to the entrance in the OR, the day of the surgery. Ketamine will be given as follows: in the i.v. ketamine infusion group, an infusion of 0.25 mg.kg-1.h-1 is started with an infusion pump and is kept at the same rate until the surgical team starts closing the deep layers of the abdominal incision. Consumption of the infusion pump is noted at T0 (incision) and at each hour during the surgery and when the infusion is discontinued. In the i.v. ketamine bolus group, 0.25mg.kg-1 of ketamine will be first administered at the time of incision (T0) then every single hour for the rest of the surgery. Study starts at anesthesia induction and incision (T0) for ketamine administration and ends when the patient leaves the PACU. Objectives of the study are cited above.

Data analysis: statistical analyses will be done using SAS version 9.4 or higher and will be performed at a two-sided 0.05 significance level.

Significance/Importance: This is the first study that will compare the impact of the classical intraoperative ketamine administered as repeated i.v. boluses versus as a continuous i.v. infusion during major surgeries lasting more than 3 hours.

Study Design: open label study, with two controlled randomized parallel groups

Subject Population: ASA 1 to 3 adult patients scheduled to undergo elective general, urologic or gynecological surgeries.

Sample Size: 50 patients will be evaluated in this study.

Study Duration: 10 months.

Study Center: Maisonneuve-Rosemont Hospital, CIUSSS de l'Est de l'Ile de Montreal, Montreal, Quebec, Canada.

Adverse Events: None expected.

Conditions

Bolus Versus Infusion Ketamine, Anesthesia Gas Consumption

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

bolus of intravenous ketamine

A bolus of 0.25mg.kg-1 of ketamine will be first administered at the time of incision (T0) then every single hour for the rest of the surgery. Study starts at incision (T0) for ketamine administration and ends when the surgical team starts closing the deep layers of the abdominal incision.

Group Type: ACTIVE_COMPARATOR

bolus of intravenous ketamine

Intervention Type: DRUG

low-dose ketamine (0.25mg.kg-1) is administered intraoperatively as bolus at incision (T0) and for each hour of anesthesia untel the end of surgery.

continuous infusion of intravenous ketamine

An infusion of 0.25 mg.kg-1.h-1 is started at T0 (incision) with an infusion pump and is kept at the same rate until the surgical team starts closing the deep layers of the abdominal incision. Consumption of the infusion pump is noted at T0 (incision) and at each hour during the surgery until the infusion is discontinued.

Group Type: EXPERIMENTAL

continuous infusion of intravenous ketamine

Intervention Type: DRUG

An infusion of low-dose ketamine (0.25 mg.kg-1.h-1) is started at T0 (incision) with an infusion pump and is kept at the same rate until the end of surgery

Interventions

bolus of intravenous ketamine

low-dose ketamine (0.25mg.kg-1) is administered intraoperatively as bolus at incision (T0) and for each hour of anesthesia untel the end of surgery.

Intervention Type: DRUG

continuous infusion of intravenous ketamine

An infusion of low-dose ketamine (0.25 mg.kg-1.h-1) is started at T0 (incision) with an infusion pump and is kept at the same rate until the end of surgery

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ASA I to III
• Patients above 18yo
• Gender female or male
• Abdominal general, urological or gynecological surgery with epidural placement

Exclusion Criteria

• BMI <18 or >35
• Chronic neurological or psychiatric disorder or history of stroke
• Use of psychotropic drugs within 2 weeks prior surgery
• Allergy to ketamine or its excipients or any drug of the anesthesia protocol of this study
• Any contra-indication or patient's refusal for epidural placement

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ciusss de L'Est de l'Île de Montréal

OTHER

Sponsor Role: lead

Responsible Party

Philippe Richebe

MD, PhD, Professor, Director of Research, Department of Anesthesiology and Pain Medicine of Maisonneuve-Rosemont Hospital, CIUSSS de l'Est de l'Ile de Montreal (CEMTL)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philippe PR Richebé, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CIUSSS Est de l'ile de Montreal

Locations

Hopital Maisonneuve Rosemont, CIUSSS de l'Est de l'Ile de Montreal

Montreal East, Quebec, Canada

Countries

Canada

References

Carrara L, Nault M, Morisson L, Godin N, Idrissi M, Fortier A, Guertin MC, Brulotte V, Fortier LP, Verdonck O, Richebe P. The impact of bolus versus continuous infusion of intravenous ketamine on bispectral index variations and desflurane administration during major surgery: The KETABIS study. Eur J Anaesthesiol. 2021 Nov 1;38(11):1168-1179. doi: 10.1097/EJA.0000000000001588.

Reference Type: DERIVED

PMID: 34474441 (View on PubMed)

Other Identifiers

2018-1482

Identifier Type: -

Identifier Source: org_study_id