Study of the Association Between Burst Suppression During Anesthetic Induction With Propofol in Cardiac Surgery in Patients Over 65 Years of Age With Postoperative Delirium
Conditions: Postoperative Delirium
Sponsor: Pontificia Universidad Catolica de Chile

 
 
 
 
Study: “Association Between Burst Suppression During Anesthetic Induction With 
Postoperative Delirium in Cardiac Surgery” 
 
NCT number: pending 
 
Document date: December 17, 2020 
 
 
 

STUDY PROTOCOL 
 
After local ethics committee evaluation, patients over 65 years of age scheduled for elective 
cardiac surgery requiring extracorporeal circulation will be invited to participate. Those who 
are interested will be interviewed by a member of the research team who, in case of 
meeting the inclusion and exclusion criteria, will obtain the informed consent signature. 
After this, routine pre-anesthetic evaluation will be carried out plus preoperative cognition 
test (MiniCog), delirium screening (CAM) and assessment of frailty using the Clinical Frailty 
Scale (CFS). 
Once in the intraoperative period, standard monitoring (EEG, NIBP, SatO2) will be 
stablished, plus installation of an arterial line with local anesthesia and a peripheral venous 
line for drug administration. A basal blood sample will be taken to study baseline 
inflammatory status (CRP). Subsequently, a SedLine® frontal electroencephalography (EEG) 
electrode (Root, Masimo) will be installed, and the patient will be asked to close his/her 
eyes to obtain a baseline recording for 5 minutes. Then, after pre-oxygenation (100% 
oxygen), the induction of general anesthesia will be initiated in a protocolized way: Fentanyl 
5-10 ucg / Kg intravenous (i.v)., Propofol 0.5 mg / kg i.v. (plus rescue of 0.5 mg / kg i.v. after 
1 minute if necessary), Vecuronium 0.1 mg / Kg i.v. and vasoactive drugs (ephedrine, 
phenylephrine or norepinephrine) to maintain mean arterial pressure (MAP) between ± 
20% of baseline. Orotracheal intubation will be carried out on a regular basis and will be 
connected to standard mechanical ventilation (Tidal volume: 6-8 ml / Kg, Respiratory Rate: 
for exhaled CO2 between 32-35 mmHg, PEEP 5). The SedLine® monitor screen will remain 
hidden from the anesthesiologist in charge during baseline recording and induction (up to 
approximately 10 minutes after endotracheal intubation). After that, this phase of the study 
will end, and anesthesia and surgery will continue. Intraoperative variables such as duration 
of surgery and anesthesia, time in extracorporeal circulation, total drug use, temperature, 
among others, will be recorded. The anesthesiologist in charge can use the SedLine monitor 
to guide the administration of anesthetics once the initial phase (induction) has been 
completed according to usual practice. Upon completion of the case, the EEG data will be 
retrieved for further analysis. 
At the end of the surgery, in post-cardiac anesthetic recovery unit (Cardiac PACU), POD 
evaluation will be performed using CAM / CAM-ICU twice a day (AM and PM) for the first 
72 postoperative hours. In addition, a structured chart review will be carried out in order to 
identify records that describe POD. Patients will be considered to have POD if they present 
a positive evaluation with CAM / CAM-ICU or if the structured chart review is positive within 
the first 3 postoperative days. 
 
 

EEG ANALYSIS 
 
We will record the EEG data using Sedtrace (SedLine®) electrodes on the forehead located 
approximately at Fp1, Fp2, F7 and F8, the ground electrode at approximately Fpz and the 
reference electrode approximately 1 centimeter above Fpz. The data will be recorded with 
a preamplifier bandwidth of 0.5 to 92 Hz, a sample rate of 89 Hz, with a resolution of 16 bits 
and 29 nanovolts. Electrode impedance will be kept less than 5 kΩ on each channel. 
For each patient, we will select 2-minute EEG segments that will represent the baseline 
period, the response to the propofol bolus (burst suppression, yes or no) and the phase of 
maintenance of general anesthesia prior to cardiopulmonary bypass. We will visually 
inspect the selected segments in both time and spectral domains to ensure data quality. 
We will calculate the multitaper spectral estimates using Matlab's Chronux toolbox with the 
following parameters: window length T = 2 seconds without overlap, product of time 
bandwidth TW = 3, number of tapers K = 5. We will equally weight the signals from Fp1, 
Fp2, F7 and F8 channels. Patients will be considered to present burst suppression if they 
present alternating episodes of spontaneous high amplitude electrical activity (bursts) 
followed by suppression periods longer  than 1 second (electrical variability <10 μV). These 
analyzes will be performed in time domain as well as spectral domain. 
 
 
 

STATISTICAL ANALYSIS 
 
Initially, we will study the association between burst suppression (yes or no) with POD (yes 
or no) using univariate logistic regression. In addition, we will perform a univariate analysis 
for known risk factors for PDO (preoperative cognition, frailty, temperature in CPB, etc). 
Subsequently, we will perform a multivariate analysis with logistic regression to study the 
association between burst suppression with POD, after confounding variables adjustment. 
We will then use our data to generate a ROC curve and determine the area under the curve, 
sensitivity, specificity, positive predictive value, and negative predictive value of burst 
suppression to predict POD. Finally, we will use our variables to create a predictive model 
of POD that includes the burst suppression and other known risk factors for POD. 
For descriptive statistics, continuous data will be presented using the mean ± standard 
deviation or the median and its interquartile range, as appropriate. In addition, the groups 
will be compared by Student's t test for independent samples or the Mann-Whitney U test 
according to their distribution. In the case of categorical data, they will be presented as 
absolute counts and their corresponding percentage. Differences will be studied using 
Fisher's test or Chi square. For the association study, univariate and multivariate linear or 
logistic regressions will be performed, as appropriate. A significance level of 0.05 with its 
respective 95% confidence interval will be considered. All calculations will be performed in 
R statistical language. 
 
Sample size calculation: With a sample of 72 subjects, we will have 80% power to detect a 
difference if the proportion of patients that present POD and burst suppression is 0.66 and 
the proportion patients that present POD and that do not present burst suppression is 0.33 
with a significance level of 0.05 using a chi-square test. Considering 10% data loss, we will 
recruit a total of 80 patients.