Changes in a composite variability index (CVI) and bispectral index (BIS) in response to standardized pain stimuli during propofol remifentanil infusion.

Measuring the two primary components of anesthesia, hypnosis and analgesia, are
crucial in an attempt to optimize both hypnotic and analgesic drug delivery.
The Bispectral Index (BIS) is an EEG derived dimensionless number between 0 and
100 that has been proven to be adequate to measure the cerebral drug effect
during hypnotic-anesthetic drug administration. It is an established mean to
prevent intraoperative awareness in the general surgical population and has
been validated in numerous clinical trials.

Aside measuring the hypnotic component of anesthesia, measuring the
nociception-anti-nociception balance during anaesthesia is considered crucial
as it might be related to clinical outcome (1-3). The balance denotes the
situation during which simultaneous opposite effects of nociceptive stimulation
and anti-nociceptive medication on the physiology of the patient occur (4).
Nociception caused by an injury or trauma during anaesthesia results in
possible arousal reactions when accurate analgesia is lacking. Arousal is
defined as a change in the hypnotic level of the patient as a result of an
ascending stimuli reaching the cerebral cortex caused by a insufficient
blockade at the subcortical level.

This *nociceptive cascade* can be blunted by administering anti-nociceptive
medication such as opioids or local anesthetics. It has been show that
analgesics decreases the variability of the BIS and blunt the increase in BIS
that follows surgical stimulation (5, 6). Similarly, increases in
electromyographic power (EMG) and its variability are associated with responses
to painful stimulation. Recently, the composite variability index (CVI) was
developed as a measure of this BIS and EMG variability. CVI is a unitless
number between 0 and 100 and defined as the sum of the Mean sBIS (with 95% CI),
the standard deviation of BIS over the previous one minute, at 15 second
intervals and the mean sEMG (with 95% CI), the standard deviation of EMG over
the previous one minute, at 15 second intervals. Previously, it has been shown
that CVI is increased in responders to skin incision and correlates with
pre-incision analgesic level. Also, it has been shown that both CVI and heart
rate increases predict somatic responses during surgery. Hereby, CVI is a
better predictor of somatic events than heart rate increases. (7, 8). Further
studies are necessary to understand whether CVI would be a clinically useful
indicator of inadequate analgesia various levels of anesthetic depth and
analgesia. Therefore, the aim of this study was to compare the accuracy of the
changes in CVI in response to a standardized noxious stimulus during various
targeted pseudo-steady-state concentrations of remifentanil and various steady
state level of BIS as guided by propofol effect compartment controlled TCI
(closed-loop).

Main objective: to compare the accuracy of the changes in CVI in response to a
standardized noxious stimulus during various targeted pseudo-steady-state
concentrations of remifentanil and various steady state level of BIS as guided
by propofol effect compartment controlled TCI (closed-loop).

Secondary objectives: to compare the changes in other vital signs such as heart
rate and blood pressure compared to CVI in response to a standardized noxious
stimulus during various targeted pseudo-steady-state concentrations of
remifentanil and various steady state level of BIS as guided by propofol effect
compartment controlled TCI (closed-loop).

prospective, randomized controlled

pseudo-steady-state concentrations of remifentanil and various steady state
level of BIS as guided by propofol effect compartment controlled TCI
(closed-loop). protocol blz.8

The induction of anesthesia (until start of surgery) will be extended with 20
minutes. The electrical nociceptive stimulus might induce a shortlasting pain
sensation in some of the patients (BIS target 70 and low concentration of
remifentanil) as these patients might be sedated but not fully anesthetised.