Clinical trial NCT04713644: Association Between Burst Suppression During Anesthetic Induction With Postoperative Delirium in Cardiac Surgery
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postoperative Delirium
Keywords: Burst Suppression
Postoperative Delirium
Electroencephalography
Propofol
Cardiac Surgery
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
First posted: 2021-01-19
Enrollment: 78
Sex: ALL
Minimum age (years): 65
Maximum age (years): 100
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients over 65 years of age undergoing cardiac surgery with cardiopulmonary bypass.

Brief summary: The population over 65 years of age will be increasingly exposed to surgical procedures that require general anesthesia. Postoperative delirium is one of the main causes of preventable postoperative morbidity in the elderly population and is a frequent event after cardiac surgery with extracorporeal circulation. The excess administration of anesthetics that potentiate the Gamma Aminobutyric A receptor, such as propofol, are related to an intraoperative electroencephalographic pattern called burst suppression that has been associated with postoperative delirium. It is unknown whether this pattern is secondary to a relative overdose of anesthetics or rather corresponds to a characteristic of a vulnerable brain that is suppressed at doses at which other patients are not. Our objective will be to determine whether burst suppression in people over 65 years of age during a standardized anesthetic induction with propofol for cardiac surgery with extracorporeal circulation is associated with postoperative delirium compared to older people who do not present it.

Detailed description: Perioperative neurocognitive disorders, including postoperative delirium (POD), are the leading cause of preventable postoperative morbidity in the elderly population. POD is an acute brain dysfunction characterized by changes in attention and cognition usually within of the first week after surgery and anesthesia. Its appearance triggers a series of events that often end in loss of independence, increased morbidity and mortality and increased health costs. It has been associated with the development of long-term cognitive impairment, including persistent dementia. Its nature is multifactorial and its pathophysiology is not yet fully elucidated.

Over administration of anesthetics that potentiate the Gamma Amino Butyric A (GABAA) receptor, such as barbiturates or propofol, is related to an intraoperative electroencephalographic (EEG) pattern called burst suppression that has been associated with POD. It is a common event after cardiac surgery with an incidence ranging from 15% to 50%. Given its adverse impact on functioning and quality of life, delirium has enormous social implications for the individual, family, community, and health care systems.

Burst suppression is a pattern observed in the EEG characterized by quasi-periodic alternations between isoelectricity (flat EEG) and brief bursts of electrical activity such as spikes, sharp waves, or slow waves. It reflects a brain state of relative cortical inactivity that is not observed during normal waking states or sleeping behaviors. This pattern can be observed associated with coma due to diffuse anoxic damage, induced hypothermia and Ohtahara syndrome epilepsy. In addition, the administration of high-dose anesthetics that potentiate the GABAA receptor produce burst suppression followed by isoelectricity. Burst suppression during maintenance of general anesthesia with anesthetics that enhance the GABAA receptor has previously been associated with POD. When propofol is administered as a bolus during anesthetic induction, older patients, can suffer burst suppression in seconds. However, it is unknown whether this pattern is secondary to a relative overdose of anesthetics or rather corresponds to a characteristic of the vulnerable brain that is suppressed at doses to which other patients do not present this pattern. At present, it is not known whether burst suppression is a modifiable risk factor for POD or an epiphenomenon or marker of other factors that cause POD. A randomized controlled clinical trial studied an EEG-guided anesthetic protocol that reduced the administration of anesthetic, diminished the incidence of burts suppression during the intraoperative period, but not the incidence of POD. Therefore, the association between bursts suppression induced by anesthetics and POD appears not to be causal.

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 65 years of age
* Undergoing elective cardiac surgery requiring extracorporeal circulation (coronary artery bypass, univalvular replacement, bivalvular and coronary artery bypass plus univalvular replacement)
* American Society of Anesthesiologists Physical Status II-III.

Exclusion Criteria:

* Body Mass Index \> 35 and \<18 Kg / m2
* Severe ventricular dysfunction (EF \< 30% or severe dysfunction measured in ventriculography)
* Emergency surgery
* Chronic use of alcohol or drug abuse
* History of Stroke
* Neurological diseases
* Endocarditis
* Positive screening for preoperative delirium.

Primary outcomes:
measure: Postoperative Delirium
timeFrame: Up to 72 hours after surgery (3 postoperative days), CAM or CAM-ICU assessed twice daily (AM/PM)
Secondary outcomes:
measure: Burst suppression during anesthesia induction
timeFrame: 20 minutes after standardized propofol administration
measure: Burst suppression during cardiopulmonary bypass
timeFrame: Through Cardiopulmonary bypass time defined as time between connection to pump to disconnection, an average of 120 minutes
measure: Preoperative Cognitive Status
timeFrame: Preoperative anesthetic evaluation
measure: Preoperative Frailty
timeFrame: Preoperative anesthetic evaluation
measure: Electroencephalogram (EEG) Alpha Power/Total Power
timeFrame: Stable anesthetic period before cardiopulmonary bypass and 20 minutes after propofol induction
measure: CRP (C Reactive Protein)
timeFrame: Blood sample collection during arterial line insertion, before anesthetic induction
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Hospital Clínico Pontificia Universidad Católica de Chile
state: Región Metropolitana
Study officials:
affiliation: Pontificia Universidad Catolica de Chile
name: Juan C Pedemonte, MD
role: PRINCIPAL_INVESTIGATOR
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