Can a New EEG Based Tool Predict Post-operative Delirium and Cognitive Dysfunction?

As the population ages and medical progress is made, many elderly patients that previously would not have been candidates for surgery are now undergoing operations. In this group of older patients, brain dysfunction after anesthesia and surgery is well recognized and categorized into two distinct clinical entities; Post-operative cognitive delirium (POD) and post-operative cognitive dysfunction (POCD).

Delirium is an acute and fluctuating deterioration in attention accompanied by either a change in cognition or arousal and is often diagnosed by criteria established in the Confusion Assessment Method (CAM). Delirium can present as hypoactive (decreased alertness, motor activity and anhedonia), as hyperactive (agitated and combative) or as mixed forms. Age and the type of operation are the major risk factors.

Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. It was previously found that the presence of cognitive dysfunction 3 months after non-cardiac surgery was associated with an increased mortality. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors are related to patient characteristics, type of operation and anesthetic management.

Despite its limitations over-anesthesia as monitored by BIS was at-least correlative with POD. Therefore it is hopeful that an even more precise evaluation of the level of anesthesia will improve POD prediction (and thereby prevention) even further.

On the other hand the measure of depth of anesthesia by itself does not provide sufficient prediction for POCD. In POCD a major role has been assigned to hippocampal damage.

The investigators have recently demonstrated that temporary hippocampal interruptions are manifested by interhemispheric desynchronization, which are recognized by our new algorithm, which monitors electrophysiological markers of attention and of perception.

The investigators have developed a unique algorithm for analyzing EEG based on the concept of monitoring perception and attention and their interhemispheric synchronization.

The aims of this proof of concept study are: (i) to find-out whether interhemispheric desynchronization of attentional processes is associated with POCD; (ii) to find out whether the level of anesthesia, is linked primary to POD and secondary to POCD.

As the population ages and medical progress is made, many elderly patients that previously would not have been candidates for surgery are now undergoing operations. In this group of older patients, brain dysfunction after anesthesia and surgery is well recognized and categorized into two distinct clinical entities; Post-operative cognitive delirium (POD) and post-operative cognitive dysfunction (POCD).

Delirium is an acute and fluctuating deterioration in attention accompanied by either a change in cognition or arousal and is often diagnosed by criteria established in the Confusion Assessment Method (CAM). Delirium can present as hypoactive (decreased alertness, motor activity and anhedonia), as hyperactive (agitated and combative) or as mixed forms. Age and the type of operation are the major risk factors.

Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. The reported incidence figures for postoperative cognitive dysfunction vary depending on the group of patients studied, the definition of POCD used, the tests used to establish the diagnosis and their statistical evaluation, the timing of testing, and the choice of control group. The diagnosis of POCD relies on the use of neuropsychological tests, including; visual verbal learning test, based on Rey's auditive recall of words, the concept shifting test, based on the trail- making test from Halstead and Reitan's neuropsychological test battery, the Stroop color word interference test , the letter-digit coding, based on the symbol-digit substitution task from the Wechsler adult intelligence scale and the four boxes test. In a large prospective multicenter cohort study, it was found that the presence of cognitive dysfunction 3 months after noncardiac surgery was associated with an increased mortality. Furthermore, patients with cognitive decline at 1 week had an increased risk of leaving the labor market prematurely and a higher prevalence of time receiving social transfer payments. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors for developing POCD are related to patient characteristics, type of operation and anesthetic management.

Cardiovascular, respiratory, hepatic, and renal insufficiency are all associated with impaired brain performance. It is theoretically obvious that an adequate intraoperative oxygen supply for all vital organs is essential if postoperative cerebral dysfunction is to be avoided. Casai et al found that brain desaturation (rSO2 decrease \<75% of baseline) occurred in 40% of elderly patients after noncardiac surgery, and the cerebral desaturation was linked with a high incidence of POCD. A recent systematic review shows that reductions in cerebral oxygen saturation (rSO2) during cardiac surgery may indicate CPB cannula malposition, particularly during aortic surgery. However, only weak evidence links low rSO2 during cardiac surgery to POCD.

POCD is a well-recognized clinical phenomenon of multifactorial origin; emboli, hypoperfusion, inflammation, and patient's preoperative cerebral dysfunction Meticulous surgical and anesthesiological techniques are important for preventing complications and keeping the risk of POCD to a minimum.

The EEG is an electrophysiological monitoring method used to record electrical activity of the brain, including normal and abnormal activity. In recent years, numerous clinical studies were performed to evaluate whether the use in intraoperative electroencephalography (EEG) to control the depth of anesthesia has any effect on POCD.

Recently it was confirmed that intraoperative neuro-monitoring for depth of anesthesia is associated with a lower incidence of delirium. However it is unrelated to the incidence of POCD. The most common available monitor for depth of anesthesia is the Bispectral index, developed more than 20 years ago. The device's output is based on electroencephalographic (EEG) signals from the frontal lobe (monitors brain activity) in combination with electromyographic (EMG) waves (monitors muscle activity). The BIS produces a number ranging from 0 -100, which matches the patient's level of consciousness (awake, sedated or unconscious) under GA. There are two main problems with the BIS device: (1) It analyzes EEG and EMG with no ability to differentiate the neuronal activity from the muscle activity. Thus, when neuromuscular blocking drugs (NMBDs) are used, scores produced by the BIS are influenced by the lack of muscle activity, and mistakenly indicate a state of unconsciousness (lack of neuronal activity) even if no hypnotic medications were used, and (2) The BIS is based solely on frontal electrodes and does not monitor posterior activity. Thus, anesthetic medications with more posterior effect (such as ketamine) receive a false score by the BIS device. Accordingly, the BIS system might be better used as a means of tracking specific anesthetic medications and not as a universal means for monitoring unconsciousness.

Despite its limitations over-anesthesia as monitored by BIS was at-least correlative with POD (but not with POCD). Therefore it is hopeful that an even more precise evaluation of the level of anesthesia will improve POD prediction (and thereby prevention) even further. On the other hand the measure of depth of anesthesia by itself does not provide sufficient prediction for POCD. In POCD a major role has been assigned to hippocampal damage.

The investigators have recently demonstrated that temporary hippocampal interruptions are manifested by interhemispheric desynchronization, which are recognized by our new algorithm, which monitors electrophysiological markers of attention and of perception. This algorithm was based on a previous set of studies, which showed the ability to decompose the entire multi-electrode EEG/ERP sample to a superposition of attention and perception processes, spread in space (over the scalp) and time (hundreds of milliseconds). Our algorithm is unique in the ability to extract the needed perceptual and attentional information indicating depth of anesthesia and hemispheric damage (manifested by interhemispheric desynchronization) in real time every 30 seconds and with a minimal electrodes setup, comprised of 6 electrodes.

The aims of this proof of concept study are: (i) to find-out whether interhemispheric desynchronization of attentional processes is associated with POCD; (ii) to find out whether the level of anesthesia, is linked primary to POD and secondary to POCD. For both purposes the investigators use a novel EEG algorithm based on the concept of monitoring perception and attention and their interhemispheric synchronization.

Eligibility Criteria:
Inclusion Criteria:

1. Patients 65 years or older undergoing elective cardiac surgery (CABG or valve replacement) or hip/knee replacement.

Exclusion Criteria:any of the following criteria;

1. inability or refusal to provide informed consent,
2. significant visual impairment so that the pictures of the confusion assessment method could not be interpreted to accurately test to assess delirium,
3. profound dementia or aphasia that interfered with the assessment of delirium,
4. inability to speak Hebrew/ Russian or Arabic so that a language barrier was not confused with postoperative confusion.
5. Any previously documented major neurologic or psychiatric dysfunction