Background The incidence of primary tumors in the central nervous system in adults in
Sweden is approximately 1400 per year. Gliomas constitutes the most common form,
approximately 50%. The neurosurgery aims at securing material for pathological-anatomical
diagnosis, reduction of symptoms, maximal reduction of tumor mass with minimal functional
impact. An important feature of neurosurgical anesthesia, apart from intraoperative
stability, is early postoperative recovery of consciousness with minimal residual
sedation. This is a key factor to enable early neurological assessment and early
discovery of postoperative complications (hematomas).
In total intravenous anesthesia the anesthesia drugs (e.g. propofol and remifentanil) are
supplied by continuous intravenous infusion. The pumps used for administration can be
programmed manually (in mg/kg/h or mcg/kg/min, manual total intravenous anesthesia,
mTIVA) or using a programmed algorithm (target controlled infusion, TCI, where the
algorithm calculates the concentration of drug at the effect site). Regardless of
programing system, the anesthetist or anesthetic nurse adjusts the programming to the
patients´ needs during anesthesia and surgery. The Neurosurgical anesthesia section of
Lund University Hospital, Lund, Sweden, uses both mTIVA and TCI and all exposed
anesthetic personnel are comfortable with both mTIVA and TCI.
Montoring of anesthetic depth is based on physiological reactions. In neurosurgical
anaesthesia access to face and pupils are restricted/absent and thus monitoring further
restricted. To add to the monitoring of anesthetic depth several processed simplified EEG
systems (pEEG) have been developed. EEG systems have proprietary underlying algorithms
and are thus not directly comparable. The recommendations regarding adequate anesthesia
dept differs considerably numerically. pEEG -systems are expected to add to the
evaluation of anesthetic depth, reduce the risk of awareness and reduce the risk of over-
anesthetizing with hypotension and prolonged recovery of consciousness during emergence.
pEEG has predominantly been assessed in other subspecialities than neuroanesthesia. In
neuroanesthesia interference of the pEEG monitoring system with the surgical field is one
factor that has to be taken into account when placing the monitoring system, especially
in frontally placed tumors.
Bispectal index (BIS, Medtronic,) is one of several commercially processed EEG systems
(pEEG). BIS is a pEEG index ranging from 0-100, where 0 corresponds to isoelectric EEG
and 100 to full alertness. Recommended anesthesia depth is 40-60 intraoperatively. The
EEG-monitoring in the BIS system is available as a unilateral strip increasing clinical
usefulness in this setting.
The aim of this study is to improve anaesthesia and monitoring for intracranial tumor
resection by evaluating the effect of pEEG monitoring for propofol/remifentanil
anesthesia delivered by manual total intravenous anesthesia (mTIVA) or target controlled
infusion (TCI).
Methods Ethical review board approval (Dnr 2024-01935-01, Stockholm, Sweden) is present.
The study is a single centre randomized trial between mTIVA and TCI with concealed
pEEG-monitoring.
A couple of days, up to two weeks peroperatively, the patient is assessed at the
preoperative neurosurgical out patient clinic. At that time an anesthesiologic
preoperative assessment is performed and elegible patients receives information about the
study and are able to give informed consent.
Patients will be randomized to mTIVA or TCI with stratification based on presence of
hypertension. Randomization (mTIVA or TCI) is performed on the day of surgery.
Monitoring, including BIS-monitoring is started prior to induction. All patients receive
propofol/remifentanil based general anesthesia with norepinephrine infusion to support
blood-pressure. Endotracheal intubation is facilitated with rocuronium. The result of the
pEEG-monitoring is concealed, but anesthesia caregiver(s) can obviously not be blinded to
mTIVA or TCI. Extubation is expected to take place in the operating room. Postoperative
level of sedation is assessed using Karolinska Sleepiness Scale (KSS) during the first
two postoperative hours. KSS is an ordinal scale assessing sleepiness during the last
five minutes from "extremely alert" to "very sleepy, great effort to keep awake, fighting
sleep". Follow up regarding awareness is performed once day 1-3 postoperatively.
Data regarding age, sex, length, weight, comorbidities, tumor location, ASA-
classification and preoperative medication will be collected. Peroperative vital
parameters and pEEG -results and data from infusion pumps are primarily collected
electronically. The manually kept anesthetic notes are copied and stored as back-up.
Times for start and end of anesthesia end surgery and time of recovery of consiousness
are collected. All individual data are de-identified and coded after collection.
Inclusion and exclusion criteria Inclusion Adult (>18 years old) Elective supra or
infratentorial tumor resection via craniotomy Cognitive function allowing informed
consent.
Exclusion Intracranial tumor with operation via biopsy Need for intraoperative
neurophysiological monitoring Tumor resection via awake surgery Tumor localization not
allowing placement of BIS electrodes due to interference with surgery Morbid obesitas.Outcomes Primary endpoint is per cent of time spent within recommended BIS- levels during
anesthesia (from preparation until end of surgery).
Secondary endpoints are: mean pEEG, time from end of surgery to extubation, peroperative
propofol/remifentanil consumption, postoperative degree of sleepiness measured with
Karolinska Sleepiness Scale (KSS) and awareness assessment.
Technical aspects of the pEEG- monitoring will be assessed with special reference to
interaction with sterile field and performance in different types of surgical positions.
An assessment of the "smart pilot view" (Dräger, Draeger Medical, Mississauga, ON,
Canada) as an indicator of time to recovery of consuiousness may be added.
Randomization Randomization will take place on the day of surgery by opening the
pre-prepared sealed randomization envelope. Randomization between mTIVA and TCI (1:1) is
stratified for hypertension.
Statistical methods and power calculation Since no similar studies were identified, a
difference between the groups (mTIVA and TCI) of 5% with an SD of 10% was used. With a
power of 80% and alpha 0,05 and 1:1 allocation 126 patients, 63 in each group should be
randomized. These figures are based on the estimation that a difference of <5% would not
be clinically significant.
The main analysis will be done according to intention to treat. Depending on distribution
parametric or non-parametric analysis methods will be used.
For the secondary endpoints differences in mean pEEG, drug use and relevant times will be
analysed. Depending on distribution parametric or non-parametric analysis methods will be
used. As primary KSS variable the KSS on arrival in the postoperative unit will be used,
a deviation of two or more units will be considererd a significant change. KSS will be
used as an ordinal scale. A per protocol analysis may be performed as a secondary
analysis. The "smart pilot view" will be analyzed comparing observed with calculated time
of regaining consciousness using a relevant test depending on distribution. Awareness
assessment will be descriptive.
