Electroencephalographic Biomarker to Predict Acute Post-operatory Cognitive Dysfunction

Electroencephalographic Biomarker to Predict the Development of Acute Post-operatory Cognitive Dysfunction States: a Protocol of an Observational Study in a Cohort of Patients From Two Centers

Acute post-operatory cognitive dysfunction states are one of the most important complications in older patients after surgery. Two acute cognitive dysfunctions have been described: postoperative delirium (PD) and postoperative subsyndromal delirium (PSSD). Patients who develop delirium, both as a complete or incomplete syndrome, have poor long-term outcomes, such as longer length of hospital stay, institutionalization at discharge, and even higher mortality, and consequently, the human and economic costs significantly increase for the health system. Here the research team will use an observational cohort, investigator blinded in two-center with a primary endpoint to validate the relative alpha power ratio as a predictive biomarker of postoperative cognitive dysfunctions.

Study Overview

• Status: Completed
• Conditions: Cognitive Dysfunction; Postoperative Delirium
• Intervention / Treatment: Device: Sedline

Detailed Description

Acute post-operatory cognitive dysfunction states are one of the most important complications in older patients after surgery. Two acute cognitive dysfunctions have been described: postoperative delirium (PD) and postoperative subsyndromal delirium (PSSD). In previous reports, the incidence of PD in older patients is between 10% to 30%, while PSSD is more frequent 30% to 50%. Patients who develop delirium, both as a complete or incomplete syndrome, have poorer long-term outcomes, such as longer length of hospital stay, institutionalization at discharge, and even higher mortality, and consequently, the human and economic costs significantly increase for the health system.

An early diagnostic and prevention of delirium are the key points to decrease the poor long-term outcomes and health costs. The diagnosis requires cognitive testing to elucidate functional patients' status before and after surgery. The need for a biomarker that may predict the occurrence of PD and PSSD and allow the selection of patients who need prevention strategies is a primary research field.

Here the research team will use an observational cohort, investigator blinded in two-center with a primary endpoint to validate the relative alpha power ratio as a predictive biomarker of postoperative cognitive dysfunctions.

To calculate the sample size, the investigators used values obtained from a previous work in a cohort of 30 patients and decided to compare the prediction ability of MoCA and alpha power ratio. ROC curves and their AUC were used to calculate the prediction ability of MoCA and alpha power ratio. Thus, a sample size of 425 patients was calculated considering an AUC of MoCA = 0.786 and AUC of alpha power = 0.895, a two-tailed test, an alpha error of 0.05 and a power of 0.8 and considering a 25% loss. Investigators consider this study as a pilot validation trial to establish the utility and the capacity of the EEG biomarker for predicting PD and PSSD, the research team aims to include the 25% of the total sample. This yields the need for 106 patients for this preliminary trial.

• Study Type: Observational
• Enrollment (Actual): 106

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile
    • Instituto Nacional del Cancer
  • Santiago, Chile, 8380456
    • Hospital Clínico Universidad de Chile

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients at risk of delirium or subsyndromal delirium after High-risk Surgery will be evaluated in the pre and postoperative period for cognitive dysfunction and the appearance of delirium syndromes. In the intraoperative period, an EEG-based monitorization will be performed using a SedLine (Masimo, CA) Monitor.

Description

Inclusion Criteria:

• Age ≥ 60 years old
• Scheduled for high-risk elective surgery
• Need for at least 3 days of hospital stay
• Surgery performed under general anesthesia
• Written informed consent for participation in the trial

Exclusion Criteria:

• Patients with preoperative delirium or dementia
• Patients using neuroleptics drug during the past 6 months
• Patients with a history of encephalopathy, psychosis, stroke or brain trauma with neurologic sequels
• The use of ketamine or dexmedetomidine during surgery
• Emergency surgery
• Mechanical ventilation during the 72 after surgery
• Analphabetism
• Patients who do not talk Spanish
• Patients included in another clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Postoperative Delirium Risk Patients; Preoperative cognitive function testing- EEG monitorization during surgery - Postoperative function testing	Device: Sedline; Intraoperative EEG monitorization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium and Subsyndromal Delirium	Incidence of Delirium and Subsyndromal Delirium in the cohort	5 Postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Number of deceased patients	Perioperative period
Delirium Severity	Delirium severity assessed by Cognitive Assessment Method - Severity	5 Postoperative days
Delirium Duration	Duration of delirium during the perioperative period	Perioperative period
Need for Mechanical Ventilation assistance	Number of patients that needed mechanical ventilation	Perioperative period
Reintervention	Number of patients that needed another surgery after primary intervention	Perioperative period
Unanticipated ICU hospitalization	Number of patients that needed unanticipated intensive care unit (ICU) care	Perioperative period

Collaborators and Investigators

• Sponsor: University of Chile
• Collaborators: Masimo Corporation
• Investigators: Study Chair: José I. Egaña, M.D./Ph.D., University of Chile

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Actual): August 4, 2022
• Study Completion (Actual): August 4, 2022

Study Registration Dates

• First Submitted: December 27, 2019
• First Submitted That Met QC Criteria: December 30, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Delirium; Postoperative Delirium; Postoperative Subsyndromal Delirium
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Delirium; Cognitive Dysfunction; Emergence Delirium
• Other Study ID Numbers: ID19I10345

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No