Methods
A comprehensive electronic search was performed in the following databases from their
inception to June 2023: PubMed, Embase, Cochrane, Scopus, Web of Science, and Google
Scholar. The literature search was performed using specific keywords: anesthesia AND
awake craniotomy OR intraoperative stimulation mapping OR direct electrical stimulation,
and asleep motor mapping OR direct cortical motor evoked potential (dcMEP). To date,
there are no articles describing anesthesia considerations during intraoperative stimulation
brain mapping. Articles were screened and included if it described the anesthesia
management during intraoperative brain mapping either AC or asleep motor mapping,
the effects of different anesthetic agents on the quality of mapping, and the causes
of failure of AC. Articles that described extraoperative mapping and AC without ISM
were excluded. Data were then extracted and organized to be presented in a cohesive
manner.
Anesthesia Considerations for Intraoperative Stimulation Mapping
Choice of Anesthetic Technique for Awake Craniotomy with Intraoperative Stimulation
Mapping
The main goal in AC is a patient who is calm, responsive, and able to perform the
tasks required during stimulation mapping to accurately identify eloquent structures.
Both the asleep-awake-asleep (SAS) technique (with general anesthesia [GA] during
the asleep phase) and conscious sedation (or monitored anesthesia care [MAC]) can
be used for ACs with ISM, provided that adequate local anesthesia (LA) is administered
to the scalp, short-acting anesthetic drugs are used, and sedative infusions are stopped
or reduced ahead of the mapping.[7] ([Table 1]) Some of the anesthetic consideration for electrocorticography (ECoG) may apply
to ISM and has been described previously.[8]
A meta-analysis by Stevanovic et al did not identify significant differences between
SAS and MAC techniques with regard to the rate of mapping failure, intraoperative
seizures (IOSs), and new neurological deficits.[9] A recent meta-analysis by Natalini et al concluded that the MAC technique had fewer
AC failures and shorter procedure time, while the SAS technique had a lower incidence
of IOSs.[10] Nevertheless, both these meta-analyses are flawed by bias due to the inclusion of
a large number of observational and retrospective studies. Therefore, anesthesia management
in ACs remains primarily guided by local practice preferences, and no one technique
is superior with regard to the quality of ISM. Some authors have suggested that the
SAS technique could be beneficial in more prolonged procedures (more than 4 hours)
to limit patient fatigue during mapping. However, to date, no evidence supports this
affirmation.[11]
[12]
Choice of Anesthetic Drugs for Awake Craniotomies
Many different drug regimens have been used in the setting of AC.[7]
[10]
[11] A commonly used anesthesia regime, as described by Sanai et al in their landmark
paper on outcomes after language mapping for glioma resection, includes premedication
with low doses of midazolam and fentanyl, followed by sedation with propofol or dexmedetomidine
with remifentanil and cessation of all anesthetics after removal of the bone flap.[13] If an SAS technique is chosen, either total intravenous anesthesia (TIVA) or volatile
may be used during the asleep phases of surgery, with most studies reported using
TIVA.[9]
[10]
[11] Recently, Kulikov et al described the use of xenon anesthesia during the first asleep
phase of SAS for AC with the advantage of a short awakening time of approximately
5 minutes.[14]
Dexmedetomidine has been proposed for theoretical and practical benefits in awake
procedures, notably because it maintains spontaneous breathing and patient cooperation[15] while allowing reliable, functional mapping and ECoG recordings.[16] In patients with supratentorial brain mass lesions, midazolam and propofol exacerbate
or unmask neurologic deficits more than dexmedetomidine at clinically equivalent sedation
levels,[17] which could, in theory, make dexmedetomidine less likely to induce false positives
during intraoperative mapping. Another retrospective study also reported more postoperative
neurological deficits in the subgroup of patients who received benzodiazepines during
their AC, partly related to the unmasking of their preoperative deficits.[18]
A randomized controlled trial (RCT) by Goettel et al found that the efficacy of sedation
and mapping quality was similar between propofol-remifentanil and dexmedetomidine
for conscious sedation during AC for supratentorial tumor resection. However, patients
in the dexmedetomidine group had a lower rate of adverse respiratory events.[19] Another RCT by Elbakry and Ibrahim comparing propofol-remifentanil with propofol-dexmedetomidine
sedation for AC for epilepsy surgery reported a higher sedation score in the propofol-remifentanil
group at the cost of more side effects such as nausea, vomiting, oxygen desaturation,
and respiratory depression.[20] A recent meta-analysis concluded that dexmedetomidine provided better surgeon satisfaction
during AC with no significant differences with propofol in other outcomes (intraoperative
adverse events, patient satisfaction, and procedure duration). However, one of the
three RCTs included in their analysis used the SAS technique; thus, the generalizability
of their results is questionable.[21]
[22]
An older observational study reported the use of a ketamine-propofol combination (ketofol)
in a 1:1 ratio mixture as part of their MAC technique during AC for tumor resection.
Adverse events occurred in 53.6% of their patient, which included hemodynamic events
(10.7%), respiratory events (7.1%), oversedation (7.1%), and seizures (7.1%).[23] These results are comparable to those reported in propofol or dexmedetomidine-based
MAC techniques. However, they did not report on the quality of ISM during the AC.[10]
[21] Although the technique sounds promising, there is inadequate evidence currently
to support this technique.
Failure of Awake Craniotomy and Intraoperative Mapping
Failure of AC is defined as an unplanned conversion to GA or a premature cessation
of intraoperative mapping. AC failures are low, reported around 2 to 3%, irrespective
of the anesthesia technique.[9]
[10] The main causes of failure of AC were intraoperative agitation or lack of compliance
during mapping (35%), followed by IOSs (13%), drowsiness or oversedation (9%), and
acute neurological deficit (7%).[10] Agitation and reduced compliance during mapping may be caused by factors such as
significant preoperative deficits, impaired cognitive status, poor motivation or tolerance
for the procedure, and fatigue from prolonged mapping. These factors can be reduced
by strict patient selection criteria, adequate patient preparation, and the presence
of a skilled multidisciplinary team.[5]
[10]
The incidence of IOSs range from 5 to 8%,[24]
[25] with only 0.5% leading to failure of AC.[9] Most IOS resolved without adverse effects to the patient.[9] A large proportion of IOS is triggered by DES of the brain.[24]
[25] A retrospective study found that risk factors for IOS include frontal tumor location,
preoperative history of seizures, preoperative radiotherapy, and, interestingly, intraoperative
use of dexmedetomidine.[25] Another retrospective analysis also reported that IOS detected via ECoG occurred
more in dexmedetomidine compared with propofol, but was not statistically significant
on univariate regression analysis with similar epilepsy outcomes at 1 year in both
groups.[24] Further studies are needed to delineate the association of dexmedetomidine with
the occurrence of IOS during AC.
IOS is usually self-limiting with cessation of the ISM. Rapid irrigation of the cortex
with cold saline will abort the seizure in most other patients, allowing the resumption
of mapping after a brief rest period. However, refractory seizures are usually treated
with intravenous benzodiazepines, propofol bolus, and antiepileptic drugs. Rarely
conversion to GA with invasive airway management may be required.[5]
[11]
[26] Overall, the combined evidence supports the notion that AC with ISM is a safe procedure
with a high success rate.[10]
Anesthesia Considerations for Motor Mapping under General Anesthesia
In recent years, there has been a growing number of studies that compare motor mapping
in awake patients versus patients under GA. Two recent meta-analyses of mainly observational
studies found similar results with either technique with regard to neurological deficits
(both early and late) and severe morbidity. However, there was a trend toward a greater
mean extent of resection in AC compared with GA (90.1% vs. 81.7%)[27] and a lower rate of permanent deficit in AC compared with GA (10.8% vs. 12.7%).[28] Both these meta-analyses concluded that glioma resection in or near the motor areas
can be safely performed with either technique.
To date, no studies have compared volatile to TIVA anesthetic technique in asleep
motor mapping. Most recent studies on motor mapping under GA reported using a TIVA
protocol, usually consisting of propofol and remifentanil infusions with muscle relaxants
avoided after intubation.[29]
[30]
[31]
[32]
[33]
[34] TIVA is recommended as the optimal anesthetic regime in the literature[35] because of the well-recognized dose-dependent effects of volatile anesthetics on
transcranial MEP (tcMEP) amplitudes,[36]
[37]
[38]
[39] which many authors postulate to elicit similar effects during direct cortical stimulation
of MEP. Low doses of volatile agents (Minimum Alveolar Concentration < 0.5) allow
acceptable tcMEP recordings for clinical interpretation in some patients.[40] Thus, volatile agents compatible with tcMEP testing[41] will likely enable the measurement of responses to cortical or subcortical DES,
as resistance to stimulation will be reduced by bypassing the skull ([Table 1]).
Nevertheless, earlier studies on asleep motor mapping used volatile anesthetic techniques.
Wood et al attempted to localize the somatosensory and motor cortex using the low
frequency (LF) stimulation paradigm described by Penfield. They successfully localized
the somatosensory and motor cortex under LA but could not localize the motor cortex
under volatile anesthesia.[42] Similarly, Vitaz et al obtained successful motor stimulation in only 50% of their
patients under volatile anesthesia using the LF paradigm, even when higher thresholds
were used.[43]
The high frequency (HF) stimulation paradigm developed by Taniguchi et al was able
to overcome the inhibition of volatile anesthetic to synaptic transmission at the
anterior horn of the spinal cord by using a stimulus of 300 to 500 Hz in trains of
5, at a much lower total charge than those produced by LF paradigm. They theorized
that this repetitive stimulation caused an accumulation of corticospinal excitatory
postsynaptic potentials in motor neurons to achieve firing thresholds even under GA.
This also allowed the detection of motor responses without causing apparent patient
movement via electromyogram recording of evoked muscle potentials.[6] Following this, Kawaguchi et al found that short-train HF stimulation successfully
evoked intraoperative MEP under isoflurane or sevoflurane anesthesia but not single-pulse
HF stimulation. They also found that intraoperative MEP changes were still detectable
under partial neuromuscular block conditions in 50% of patients.[44]
It should be highlighted that studies on subcortical HF motor mapping that detailed
their anesthetic regime have used only TIVA (propofol-remifentanil) regime. Thus,
the correlation between motor threshold (MT) intensity and distance from the corticospinal
tract (CST) may not apply to a volatile anesthetic technique.[30]
[31]
[32] If low MTs are reached, the CST is expected to be very close, and depression of
the MEP response secondary to volatile anesthetics could, in theory, lead to damage
to these tracts. Two recent small retrospective studies showed that asleep motor mapping
(cortical and subcortical) can be safely performed using triple motor mapping (using
DES, tcMEP, and dcMEP) and volatile anesthetic regime with either sevoflurane, desflurane,
or isoflurane in 50 to 70% nitrous oxide at less than 0.5 minimum alveolar concentration
and remifentanil,[45] or a mixed TIVA and sevoflurane technique with an end-tidal average of 0.7%.[46] Since HF subcortical motor mapping is still a developing technique, the inclusion
of volatile agents during GA with motor mapping should be discussed with the neurosurgical
team. It may be justifiable if the triple motor mapping technique is employed.
Ketamine and etomidate have been successfully used during tcMEP in spine surgery.[47]
[48]
[49]
[50] Two recent RCTs in elective spine surgery reported that ketamine in subanesthetic
dose (0.5 mg/kg/h) and ketofol (in 1:4 mixture) improved tcMEP amplitudes without
affecting latency when compared with dexmedetomidine and propofol.[51]
[52] On the contrary, a 1 mg/kg bolus dose of ketamine significantly suppressed tcMEP.[53] Extrapolating these findings from tcMEP, low-dose ketamine may have a role in augmenting
dcMEP signals, especially during intraoperative loss of signals after optimizing all
other physiological parameters. Nonetheless, these agents have not been directly investigated
during asleep motor mapping.
Somatosensory evoked potential (SSEP) signals are less sensitive to anesthetics, and
reliable signals can be obtained with lower MAC concentrations of volatile agents.
Since SSEP phase-reversal uses an electrode grid directly applied to the cortex, recorded
signals are more reliable than transcortical SSEP.[42]
[54] Reliable SSEP phase reversal has been performed using 0.5 to 1.0% isoflurane with
60% N2O.[42]
[54] Muscle relaxants can improve the quality of SSEP signals but are generally avoided
during SSEP phase reversal since motor mapping with DES usually follows.
Conclusion
ISM is the gold standard for resection of lesions within or adjacent to eloquent brain
tissue with various outcome benefits. AC with MAC is frequently utilized during ISM
due to the feasibility of intraoperative language, motor, and neurocognitive testing.
Various anesthetic regimens are compatible with awake functional mapping, although
dexmedetomidine may have an advantage over other sedative agents. On the contrary,
intraoperative motor mapping can be performed both under awake and asleep conditions.
While TIVA has been the standard anesthetic regimen of choice in most recent studies
in asleep motor mapping, the role of low-dose volatile anesthetics could be found
in this clinical context, especially with the high-frequency stimulation paradigm
and triple motor mapping. Further studies are required to investigate the effects
of volatile anesthetics on subcortical motor mapping and find its role in future asleep
motor mapping.
Table 1
Summary of anesthesia considerations for intraoperative stimulation mapping
|
Awake craniotomy
|
Asleep motor mapping
|
|
Anesthesia technique
|
Monitored anesthesia care (MAC)
OR
Asleep-awake-asleep (SAS)
Similar outcomes and quality of mapping, but SAS may be advantageous in longer procedures
|
Total intravenous anesthesia (TIVA) preferred
|
|
IV anesthetic agents
|
Various combinations may be used for sedation:
Propofol-remifentanil
Propofol-dexmedetomidine
Dexmedetomidine has the advantage of lower adverse respiratory events, improved patient
cooperation, and surgeon satisfaction
Benzodiazepine may unmask preoperative neurological deficits
|
Propofol-remifentanil combination is commonly used during TIVA
|
|
Volatile agents
|
N/A
|
Minimum Alveolar Concentration less than 0.5 may be used if a triple motor mapping
technique is performed (DES, dcMEP, and tcMEP)
|
|
Muscle relaxants
|
N/A
|
Avoid after intubation
|
Abbreviations: DES, direct electrical stimulation; dcMEP, direct cortical motor evoked
potentials; IV, intravenous; N/A, not available; tcMEP, transcranial motor evoked
potentials.
