Delirium Clinical Trial
Official title:
The Association Between Minor Brain Injuries and Level of Anesthesia Detected by a New EEG Based Tool, to Delirium and Post-operative Cognitive Dysfunction After Cardiac and Non-cardiac Surgery - a Proof of Concept Study
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.
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