Dose-response Curves Between Propofol and Intraoperative Electroencephalographic Patterns

Determination of Dose-response Curves Between Propofol Concentration and Intraoperative Electroencephalographic Patterns Until Burst Suppression

In the world, 230 million surgeries are performed per year and a significant part is performed in patients over 65 years of age. These patients are more labile, especially from the neurocognitive point of view with a high risk to develop neurocognitive complications, such as postoperative delirium. Recent studies have linked this type of complication with an overdose of general anesthetics during surgery. For this reason, in recent years, the use of brain function monitors during the intraoperative period has been recommended to adapt the dosage of the drugs to each patient and thus to avoid overdosing of general anesthetics. However, to date, the available monitors that process the electroencephalographic signal are not able to adequately discriminate gradual changes in anesthetic depth. Also, no systematic studies have been performed that analyze changes that occur in the electroencephalogram (EEG) signal secondary to increases in complications from general anesthetics. Thus, the investigators design this study with the main aim to determine the changes in electroencephalographic patterns induced by a stepped increase of propofol until the burst suppression is reached.

Study Overview

• Status: Completed
• Conditions: Propofol Overdose; EEG
• Intervention / Treatment: Drug: Propofol; Device: Electroencephalogram recording

Detailed Description

The investigators will carry out a prospective analytical observational clinical study at the Clinical Hospital of the University of Chile. In total 15 patients will be recruited, in who a frontal electroencephalographic signal will be recorded using a SedLine® monitor, and propofol concentration will be estimated using the Marsh model. First, the concentration of propofol at the loss of consciousness (LOS) will be recorded in the presence of remifentanil (7.5 ng/mL). Then, patients will be intubated and remifentanil will be decreased to 4 ng/mL. After that, the concentration of propofol that caused the LOS will be maintained for 20 minutes. Finally, propofol will be increased in steps of 0.3 mcg/mL for 7 min, until an episode of burst suppression will be observed. In the complete protocol, EEG activity will be acquired using a SedLine® monitor.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Chile
  • RM
    • Santiago, RM, Chile, 7690306
      • Centro de Investigación Cínica Avanzada (CICA), Hospital Clinico de la Universidad de Chile
    • Santiago, RM, Chile, 7690306
      • Hospital Clinico de la Universidad de Chile

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) Physical Status 1 or 2
• Low-risk surgery

Exclusion Criteria:

• BMI > 35 kg/m2
• Benzodiazepines use
• Epilepsy
• Psychiatric disorder
• Kidney disease
• Liver disease
• Brain damage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose-response; - Concentration of propofol at the loss of consciousness (LOS) will be recorded in the presence of remifentanil (7.5 ng/mL) (LOS time).; - Patients will be intubated and remifentanil will be decreased to 4 ng/mL.; - Concentration of propofol that caused the LOS will be maintained for 20 minutes (Baseline time).; - Propofol will be increased in steps of 0.3 mcg/mL for 7 minutes until an episode of burst suppression will be observed (Burst suppression time). EEG activity will be acquired using a SedLine® monitor during the complete protocol.

Drug: Propofol; Stepped propofol concentration after 20 min of LOS; Other Names: Dosage increase; Device: Electroencephalogram recording; Acquisition of EEG activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the alpha power of EEG Spectrogram	% of change	Change between baseline time (0 minutes) and burst suppression time (35 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the delta power of EEG Spectrogram	% of change	Change between baseline time (0 minutes) and burst suppression time (35 minutes)
Change in the coherence	% of change	Change between baseline time (0 minutes) and burst suppression time (35 minutes)
Change in the propofol concentration	concentration in mcg/mL	Change between baseline time (0 minutes) and burst suppression time (35 minutes)

Collaborators and Investigators

• Sponsor: University of Chile
• Investigators: Principal Investigator: Jose I Egaña, MD/PhD, University of Chile; Principal Investigator: Felipe Maldonado, MD, University of Chile; Principal Investigator: Rodrigo Gutierrez, MD/PhD, University of Chile; Principal Investigator: Antonello Penna, MD/PhD, University of Chile

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2018
• Primary Completion (Actual): February 26, 2020
• Study Completion (Actual): February 26, 2020

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 13, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: EEG; Propofol; Burst suppression; General anesthesia
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Substance-Related Disorders; Drug Overdose; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: OAIC 938/18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes