Documente Academic
Documente Profesional
Documente Cultură
Neuroanesthesiology Update
Jerey J. Pasternak, MD and William L. Lanier, MD
Abstract: We provide a synopsis of innovative research, recurring themes, and novel experimental ndings pertinent to the
care of neurosurgical patients and critically ill patients with
neurological diseases. The following broad topics are covered:
general neurosurgery, spine surgery, stroke, traumatic brain
injury, anesthetic neurotoxicity, perioperative cognitive dysfunction, and monitoring.
Key Words: neuroanesthesia, spine surgery, traumatic brain injury, neurological monitoring, anesthetic neurotoxicity, postoperative cognitive dysfunction, stroke, intracranial hemorrhage,
subarachnoid hemorrhage
(J Neurosurg Anesthesiol 2016;28:93122)
GENERAL NEUROANESTHESIOLOGY
Improved operating room eciency decreases cost
and may reduce patient anxiety by reducing waiting times
before surgery. In addition, ecient time management
may also reduce work-day length and improve employee
satisfaction. Mathews et al1 reported the eect of a performance improvement project at a single institution with
a high-volume neurosurgical practice on the rate of ontime room starts. The work group: (1) streamlined the
admission process to reduce paperwork, (2) set expectations that admission by nursing services would be completed within 30 minutes, (3) assumed that the operating
room was ready on time unless a reason for delay was
communicated, (4) instituted a huddle by nursing (ie, to
communicate patient status and planned activities) 30 to
45 minutes before the expected start time, and (5) provided daily feedback to the team about rates of on-time
starts from the prior day. A room start was considered
delayed if the patient was brought into the room
>5 minutes after the expected start time. During the
study period, 2328 elective neurosurgical cases and 22,985
non-neurosurgery cases were performed. Initially the rate
of on-time starts for neurosurgical procedures was 33%.
Following implementation of the performance improvement project, the rate of on-time starts increased to 68%
Received for publication December 31, 2015; accepted January 6, 2016.
From the Department of Anesthesiology, Mayo Clinic College of
Medicine, Rochester, MN.
The authors have no conicts of interest to disclose.
Reprints: Jerey J. Pasternak, MD, Department of Anesthesiology,
Mayo Clinic College of Medicine, 200 First Avenue SW, Rochester,
MN 55905 (e-mail: Pasternak.jerey@mayo.edu).
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
J Neurosurg Anesthesiol
www.jnsa.com |
93
J Neurosurg Anesthesiol
Perello-Cerda et al12 prospectively compared hemodynamic and stress responses during emergence from general anesthesia following craniotomy between patients
with a tracheal tube in place and those in whom the
tracheal tube was changed to an LMA before emergence
from anesthesia. Patients were excluded if there was difculty with initial tracheal tube placement, increased risk
for aspiration, or poorly controlled preoperative hypertension. Forty-two patients were randomized to either
having their tracheal tube left in place or removed and
replaced with a ProSeal LMA (Laryngeal Mask Ltd, Le
Rocher, Victoria, Mahe Seychelles) immediately after the
Mayeld head holder was removed. All patients underwent a standardized anesthetic that consisted of propofol
and remifentanil infusions, and propofol dose was adjusted to maintain a bispectral index (BIS) of 40 to 60.
Muscle paralysis was achieved with a rocuronium infusion. All infusions were terminated after the Mayeld
head holder was removed, and sugammadex was then
administered to reverse neuromuscular block. The tracheal tube or LMA was removed when eective spontaneous ventilation was present and the patient was able to
follow commands. Patients who had a tracheal tube left in
place had a higher average mean arterial pressure (MAP)
(11.9 mm Hg; 95% CI, 2.1-21.8 mm Hg; P = 0.017),
higher average systolic blood pressure (SBP) (35.6 mm
Hg; 95% CI, 8.9-62.3 mm Hg; P = 0.009), and higher
average heart rate (HR) (7.2 beats per minute; 95% CI,
0.7-13.7 beats per minute; P = 0.03) compared with the
group with an LMA in place during the rst 60 minutes
following Mayeld removal. Nine (42%) patients with a
tracheal tube in place required treatment with antihypertensive medications during emergence compared
with only 3 (14%) patients with an LMA in place
(P = 0.04). Although there were no dierences in middle
cerebral artery blood ow velocity between groups, those
with a tracheal tube in place had signicantly higher regional cerebral oxygen saturation (rSO2) (mean dierence
in regional oxygen saturation = 26.1%; 95% CI, 9.1%43.2%; P = 0.002). Although the authors stated that the
tracheal tube or LMA was removed, they did not report
the median and range of the time to airway device removal. This may have confounded the results because a
tracheal tube left in place longer may have contributed to
the longer duration of more extensive hypertension and
tachycardia. Coughing during emergence was much more
common in patients with a tracheal tube in place (88%)
than in those with an LMA (10%, P < 0.001). There were
no intracranial hemorrhagic (ICH) complications in any
patient. Although exchange of a tracheal tube to an LMA
decreased hemodynamic responses and coughing, this
technique can only be applied to select patients. Further,
if adverse airway issues arise during airway exchange, this
can result in signicant hemodynamic perturbations and
hypoxia that can potentially have adverse consequences.
The additional cost of an LMA must also be considered.
The LMA-Supreme (Teleex, San Diego, CA) is an
inatable LMA that also allows for advancement of
a suction catheter into the esophagus. The I-gel LMA
94 | www.jnsa.com
(Intersurgical Inc, Jiangsu, China) also allows for a suction catheter to be advanced into the esophagus but is
composed of a solid thermoplastic polymer and changes
contour to adjust to t into the supraglottic region; it does
not require ination. The LMA has been used in patients
having procedures performed in the prone position.13
Kang et al14 reported on the use of an LMA during prone
lumbar spine surgery and compared the ecacy and
safety of the LMA-Supreme and I-gel LMA. A total of
264 patients having elective simple lumbar spine surgery
were randomized to have an LMA-Supreme or I-gel
LMA placed following induction of anesthesia and before
turning the patient to the prone position. Patients were
not included if they were obese (body mass index
[BMI] > 30 kg/m2), had high risk for airway management
diculty, or were at risk for gastric aspiration. Mechanical ventilation was used in all patients with a tidal
volume of 8 mL/kg and a respiratory rate adjusted to
maintain normocarbia. Patients with an I-gel LMA more
frequently required >1 attempt to position the device
(18% vs. 3% in the LMA-Supreme group, P < 0.001).
No patient had to be rotated back to supine for airway
management after being placed prone. There were no
episodes of aspiration, laryngospasm, or hiccoughs.
However, in this small study, despite no signicant
complications, there are still potential dangers to performing prone procedures with a supraglottic airway device in place. These can include diculty maintaining a
seal and loss of tidal volume, aspiration, and risk for
emergent airway management in the prone position with
limited, if any, airway access.
Klug et al15 reported a novel technique for airway
management in patients undergoing thermal ablation of
the gasserian ganglion to treat trigeminal neuralgia. The
technique was designed to allow simultaneous mechanical ventilation and communication with the patient
without encroaching on the surgical location. Following
induction of general anesthesia and conrmation of
mask ventilation, a 5.0 mm internal diameter tube was
advanced through the nose to a distance of 16 to 17 cm
(measured at the nare) and the cu tube was inated.
This depth likely placed the tip of the tube at or immediately above the vocal cords, as mean distance from the
nare to the glottic opening is reported to be 18.3 and
16.3 cm in adult males and females, respectively.16 Patients airways were then insuated with 100% oxygen
at 18 L/minute to compensate for gas volume loss
through the mouth. Anesthesia was maintained with
intermittent boluses of propofol and fentanyl. The patient was allowed to emerge from anesthesia following
puncture of the ganglion to conrm painful stimuli to
the surgeon. After that, general anesthesia was induced
again to facilitate thermal destruction of the ganglion.
The authors reported no episodes of oxygen desaturation, hypercapnia (venous blood samples were obtained
at intervals during the procedure), or other adverse
events. This technique is likely only suitable for select
patients such as those without obesity, without prior
airway or nasal surgery, and at low risk for gastric
Copyright
J Neurosurg Anesthesiol
aspiration. We also question whether adequacy of ventilation can be assessed by venous blood gas data.
Ablative procedures performed on the trigeminal
ganglion can be associated with signicant cardiovascular
perturbation due to the trigeminocardiac reex. Not only
are increases in vagal outow common (resulting in
bradycardia and hypotension), but hypertension can
also occur in the setting of both bradycardia and tachycardia.17,18 Wang et al19 reported that, during balloonfacilitated ablation of the trigeminal ganglion, SBP
increased from a baseline of 112 28 to 168 21 mm Hg
(P < 0.001), diastolic blood pressure (DBP) increased
from 66 18 to 99 21 mm Hg (P < 0.001), and HR
decreased from 66 11 to 52 14 bpm (P < 0.001), despite the administration of atropine 0.5 mg intravenously,
before balloon ination. The SBP and DBP responses to
balloon ination were both attenuated (leading to no
signicant change from baseline) by instituting an infusion of sodium nitroprusside at 0.5 mg/kg/minute before
balloon ination. Heart rate still decreased in those who
received sodium nitroprusside along with 0.5 mg atropine
(from 62 9 to 50 13 bpm, P < 0.001). We refer interested authors to a recent review of the trigeminocardiac reex where Chowdhury et al20 discuss its
epidemiology, pathophysiology, and management.
Theoretically, shorter-acting anesthetic drugs should
allow for faster recovery from general anesthesia, although
this is not consistently supported in the literature.21 Ghoneim et al22 prospectively compared the rapidity of emergence from anesthesia in pediatric patients who underwent
supratentorial tumor resection during either isourane,
sevourane, or desurane general anesthesia. Sixty patients
ages 7 to 18 years were randomly allocated to receive one of
the 3 inhaled anesthetics in addition to fentanyl through
continuous infusion (0.5 mg/kg/h). Inhaled anesthetic dose
was begun at 1 minimum alveolar equivalent (MAC) and
adjusted to maintain MAP within 20% of baseline values.
Inhaled anesthetic drugs were discontinued upon removal
of the Mayeld head holder, but there were no reductions
in concentrations before this. Emergence characteristics
were more favorable in patients who received desurane
and sevourane as shown in Table 1. There were no differences among groups in neurosurgeon-assessed brain
volume, systemic hemodynamics, postoperative nausea and
vomiting (PONV), or shivering. We feel that a limitation of
this investigation was that it did not reect standard
practice. Specically, anesthesiologists are likely to reduce
the concentrations of longer-acting medications earlier before emergence from anesthesia. Therefore, it was not surprising that emergence from anesthesia required a longer
duration in patients who received a longer-acting inhaled
anesthetic. As such, it is unclear how these data can be
applied to clinical practice.
Cerebral arterioles will regulate their diameter in
response to systemic blood pressure and the tension of
oxygen and carbon dioxide in blood. We refer the reader
to a review of the responsiveness of the cerebral vasculature to carbon dioxide tension published in 2015.23 Some
drugs also impact cerebrovascular resistance. This can
Copyright
Neuroanesthesiology Update
occur either directly by inducing vasodilation or vasoconstriction or indirectly by causing changes in cerebral
metabolism that aect cerebrovascular resistance through
ow-metabolism coupling. For example, midazolam decreases CBF through ow-metabolism coupling.24 One
would expect that administration of umazenil will reverse
this eect. In 16 healthy male subjects, Ogawa et al25
studied the eect of midazolam followed by umazenil on
CBF velocity and cerebral autoregulatory capacity. Midazolam was administered intravenously in 0.5 mg aliquots
every 2 minutes until the patient achieved a modied
Observers Assessment of Alertness/Sedation (OAA/S)
Score of 3 (ie, responds to name if called repeatedly or
loudly). Flumazenil was administered 30 minutes following the last dose of midazolam in 0.1 mg aliquots until an
OAA/S score of 5 (ie, responds to name on rst attempt if
spoken in normal tone) was achieved. Vital signs (including arterial blood pressure waveform obtained with a
noninvasive monitor [JENTOW 7700; Colin, Aichi, Japan]), and middle CBF velocity, were recorded at 6-minute intervals before administration of midazolam, after
midazolam but before umazenil, and then again after
umazenil. A transfer function analysis was conducted
from these data, allowing quantication of the ability of
the distal cerebral arterioles to buer changes in systemic
blood pressure. The mean doses of midazolam and umazenil were 2.4 0.5 and 0.24 0.07 mg, respectively.
Midazolam caused decreases in MAP, CBF velocity, and
transfer function gain (indicating improved autoregulatory capacity). Although umazenil antagonized the
sedative eect and eect on blood pressure induced by
midazolam, it led to a further decrease in middle CBF
velocity and transfer function gain (indicating an even
greater improvement in autoregulatory capacity). Although there were statistically signicant changes in endexpired carbon dioxide tension, the extent of changes may
be clinically inconsequential. However, the authors did
not measure arterial blood carbon dioxide tension. Arterial values may have provided a more accurate estimate of
changes in ventilatory status that, in turn, could impact
middle CBF velocity and the integrity of autoregulation.
Dexmedetomidine is commonly used for sedation during neurosurgical procedures, for example, awake craniotomy and during deep brain stimulatorlead implantation.26,27
www.jnsa.com |
95
J Neurosurg Anesthesiol
96 | www.jnsa.com
97.2 4.9
95.3 11.8
95.1 7.7
Control
Group
(n = 22)
96.6 7.4
P
0.776
88.5 11.5
0.061
106.1 8.5 < 0.01
84.6 1.2
92.2 6.4
< 0.01
92.5 11.4
114.5 9.3
< 0.01
87.6 8.8
104 8.9
< 0.01
82.3 9.2
84.9 9.3
103.5 6.9
115.7 7.0
< 0.01
< 0.01
81.2 0.0
106.8 7.0
< 0.01
83.1 7.6
104.7 4.6
< 0.01
85.1 0.9
101.5 4.3
< 0.01
J Neurosurg Anesthesiol
Neuroanesthesiology Update
www.jnsa.com |
97
J Neurosurg Anesthesiol
98 | www.jnsa.com
SPINE
Traumatic spinal cord injury presents a considerable
burden to society in terms of disability and health care cost.
Copyright
J Neurosurg Anesthesiol
Neuroanesthesiology Update
www.jnsa.com |
99
J Neurosurg Anesthesiol
100 | www.jnsa.com
STROKE
Stroke remains a major source of morbidity and
mortality. It is now the second leading cause of death
worldwide, and survivors of stroke represent the third
leading cause of disability.88,89 Ischemic strokes account
for approximately 87% of all strokes, thus contributing
greatly to the worldwide stroke burden.90 We refer the
reader to 2 consensus statements endorsed by the Society
for Neuroscience in Anesthesiology and Critical Care on
perioperative management of patients at high risk for
stroke and care of patients having endovascular treatment
of acute stroke.91,92 Also, because current management of
ischemic stroke begins with prevention through risk-factor reduction, we refer the reader to a review article that
addresses recent advances in stroke prevention.93
In those who suer an ischemic stroke, acute treatment focuses on reestablishing blood ow to injured yet
viable brain tissue (ie, the ischemic penumbra). This treatment may include intravenous administration of thrombolytic drugs, intra-arterial administration of thrombolytic
drugs, or mechanical thrombectomy. Although some
early research suggested a benet from mechanical
thrombectomy in patients with anterior circulation stroke, 3
more recent studiesall published in the New England
Journal of Medicine in 2013found no benefit in this scenario.9496
We identied 5 additional articles,97101 all published in the New England Journal of Medicine in 2015,
that described prospective randomized trials in patients
who had acute ischemic stroke and in whom treatment
consisted of medical therapy with or without mechanical
thrombectomy. We will discuss these articles individually.
In the Multicenter Randomized Clinical Trial of
Endovascular Treatment for Acute Ischemic Stroke in the
Copyright
J Neurosurg Anesthesiol
Neuroanesthesiology Update
www.jnsa.com |
101
J Neurosurg Anesthesiol
102 | www.jnsa.com
J Neurosurg Anesthesiol
Neuroanesthesiology Update
www.jnsa.com |
103
J Neurosurg Anesthesiol
104 | www.jnsa.com
12 European countries. Seventy-two percent of centers admitted all patients with aneurysmal SAH to the intensive
care unit, but this rate varied with the highest rate in Germany (98%) and lowest in Italy (47%). Eighty-two percent
of centers treated aneurysms within 24 hours of admission.
Coiling was more commonly used than clipping, but 19% of
centers still had a high-volume clipping practice (dened as
>60% of aneurysms are clipped). Most centers used total
intravenous anesthesia for either clipping or coiling, <4%
utilized induced hypothermia, and 34% used pharmacologically induced burst suppression during surgical or interventional procedures. Nimodipine, statins, and magnesium
sulfate were given to all patients in 97%, 21%, and 20% of
practices, respectively. For patients with cerebral vasospasm,
44% utilized triple H therapy (ie, hypertension, hemodilution, and hypervolemia), whereas 22% used just hypertension and induced hypervolemia without specic serum
hemoglobin concentration targets.
Treatment of ruptured aneurysms is generally performed within 72 hours of rupture.138,139 The decision to
perform clipping or coiling of ruptured aneurysms depends on multiple factors including institutional practice
pattern, aneurysm morphology, and patient comorbidities. Perioperative management of patients having these 2
procedures can be very dierent due to dierences in
surgical stress and risk for various complications. Mutoh
et al140 measured various hemodynamic variables in the
postoperative period following either clipping or coiling
of intracranial aneurysms. The study design was a post
hoc analysis of prospectively collected data from other
trials conducted by the authors. All patients underwent
aneurysm treatment within 24 hours of rupture. All patients received a standardized general anesthetic and
standardized uid management that consisted of a crystalloid solution administered at 1 to 2 mL/kg/h to maintain euvolemia. Postoperatively, uid was administered to
maintain hemodynamic stability and guided by the
PiCCO monitor (Pulsion Medical, Munich, Germany)
that allows for real-time estimation of cardiac output
from contour analysis of the arterial waveform and both
global end-diastolic volume (GEDV) and extravascular
lung water content (EVLW) through thermodilution.
Hemodynamic stability was dened as a cardiac index
Z3L/min/m2, GEDV Index Z680 mL/m2, and EVLW
Index r14 mL/kg. An established protocol was used to
manage uids to achieve these target values, and we refer
the reader to the manuscript for specic details. Of note,
the protocol included increased uid administration for
patients who developed vasospasm. Overall, 38 and 35
patients who underwent, respectively, clipping and coiling
were included in the study. Groups were well matched for
demographics, aneurysm location, and SAH severity.
Compared with coiling, clipping was associated with
greater intraoperative uid administration, greater intraoperative blood loss, and a longer procedural duration.
Postoperatively, compared with coiling, clipping was associated with a higher cardiac index and hypovolemia (ie,
GEDV Index <680 mL/m2), but only immediately postoperatively. Greater uid administration was required
Copyright
J Neurosurg Anesthesiol
Neuroanesthesiology Update
www.jnsa.com |
105
J Neurosurg Anesthesiol
106 | www.jnsa.com
J Neurosurg Anesthesiol
jugular bulb oximetry, and cerebral oxygen partial pressure measurements, were not as commonly used.168 In
China, Yuan et al169 retrospectively evaluated outcome
from 1443 patients with TBI in whom ICP monitoring
was either used or not used while receiving care in one of
22 hospitals. ICP monitoring was instituted in 838 patients and consisted of either intraventricular (51%), intraparenchymal (30%), or subdural (18%) monitoring.
Patients who received monitoring were more likely to
have: (1) a decrease in GCS over the rst 24 hours after
injury, (2) a Marshall CT score of III-IV (denoting diuse
injury with no focal lesion of >25 cm3 in volume present),
(3) major extracranial trauma, (4) the presence of subdural hematoma, (5) major intraparenchymal pathology,
(6) received care at a major trauma center, or (7) received
care at a hospital where ICP monitoring is common. An
ICP > 20 mm Hg was observed in 69% of patients during
monitoring. Overall, management was guided by Brain
Trauma Foundation Guidelines. Data analysis determine
that patients who received ICP monitoring were generally
sicker, and the use of ICP monitoring was not associated with an increased mortality or unfavorable outcome at 6 months following injury. This was also true
when only comparing those patients with a GCS of 3 to 5
on admission. Use of ICP monitoring was independently
associated with signicantly reduced mortality in those
who had: (1) a GCS of 3 to 5 on admission, (2) worsened
neurologically during the rst 24 hours, and (3) expected
high mortality. These data suggest that ICP monitoring
may improve outcome following TBI; however, data
interpretation was confounded by the fact that ICP
monitoring was more commonly used at major trauma
centers where one would expect better resources and
greater experience in dealing with TBI. Regardless of the
outcomes, results of this original research study appear in
agreement with results from a recent meta-analysis by
Yuan et al.170 Analysis of data on the utility of ICP
monitoring in TBI in 24,792 patients discovered no improvement in mortality. However, when only studies
published in 2012 or later were analyzed, patients having
ICP monitoring had signicantly lower odds of death.
The authors attributed this benet to greater compliance
with brain trauma management guidelines. However,
Banik et al171 found no dierence in outcome when
comparing children below 12 years old who did or did not
have ICP monitoring following severe TBI.
Although guidelines serve to provide management targets, patients dier in their baseline extent of injury and impairment. As such, there may be some utility in individualizing
the management of TBI by using treatment modalities targeted to the individual patient. One of the most commonly
used means of individualized management of patients with
TBI involves determining the extent of impairment of cerebral
autoregulatory capacity and optimizing of cerebral perfusion
pressure. Such an approach may determine the pressure reactivity index (PRx), a correlation coecient between MAP
and ICP. PRx ranges in values from 1 to +1, where a
negative values indicate intact autoregulation (ie, as MAP increases, cerebral vasoconstriction produces a decrease in ICP)
Copyright
Neuroanesthesiology Update
www.jnsa.com |
107
J Neurosurg Anesthesiol
108 | www.jnsa.com
glucose had signicantly faster rates of hind paw retraction following limb extension. Also, rats that received
glucose exhibited a 30% attenuation of cortical injury
volume at 15 days following brain injury. Unfortunately,
serum glucose concentrations were not measured in this
investigation, an issue that has importance because 2 mL/
kg of 50% glucose represents a large glucose load. It is
unclear whether serum glucose concentrations in the animals resulted in mild, moderate, or severe hyperglycemia.
Sedation is frequently required in patients with brain
injury. In addition to providing patient comfort, sedation
medications can also decrease cerebral oxygen consumption, cerebral glucose consumption, and ICP. However, use of sedatives has not led to improved outcomes,
although a potential bias may confound these ndings
because there may be an association of dierential requirement of sedations in patients who have greater brain
injury.184 Hertle et al185 compared retrospectively acquired
cerebral microdialysis glucose concentrations between
patients who did and did not receive sedation. Sedation
medications included midazolam, fentanyl, sufentanil,
propofol, and ketamine. In patients with normal microdialysate glucose concentrations (ie, Z1 mmol/L), only
midazolam had a signicant dose-dependent relationship
with glucose measurements. Specically, as midazolam
dose increased, glucose concentration increased, probably
as a result of diminished glucose utilization by the brain
after drug-induced metabolic depression. However, in
patients with critically low microdialysate glucose concentrations (ie, <1 mmol/L), glucose concentration was
independent of drug dose for all 5 sedative drugs. This may
occur because of increased metabolism following brain
injury, leading to increased glucose utilization and lower
microdialysate glucose concentrations that cannot be
suppressed by sedative medications.
Cognitive dysfunction is common following TBI
and can be a major factor that can impair return to
preinjury lifestyle in patients who suered TBI.186 Following TBI, neuronal apoptosis in the hippocampus may
occur in concert with cognitive dysfunction, and proliferation of neuronal progenitor cells in this region may
play a role in post-TBI repair.187189 Peptide-6 is a neurotrophic peptide that is reported to increase neurogenesis
in the dentate nucleus in normal mice and transgenic
murine models of Down syndrome and Alzheimer disease.190192 Chohan et al193 administered either peptide-6
or placebo to mice each day for 30 days following controlled cortical impact. Animals that received peptide-6
exhibited an 80% increase in the number of progenitor
cells that dierentiated into mature neurons and an 18%
decrease in neuronal apoptosis in the dentate gyrus of the
hippocampus. In peptide-6-treated animals, there was
also increased expression of microtubule-associated protein-2 (a marker of dendrites) and synaptophysin (a
marker of synaptic density) in the dentate gyrus. Peptide6 did not aect the concentration of hyperphosphorylated
tau protein. Tau protein is an important structural
component of neuronal microtubules. Hyperphosphorylated tau protein is unable to support microtubule
Copyright
J Neurosurg Anesthesiol
Neuroanesthesiology Update
FIGURE 3. Influence of inspired oxygen fraction on cerebral microdialysate glutamate concentration. Data illustrated for all 1130
samples (A), those obtained only when the PbtO2 Z20 mm Hg (B), and those where PbtO2 < 20 mm Hg (C). Mean value and 95%
confidence intervals are illustrated. *P < 0.05 and **P < 0.01 compared with those with FiO2 < 40 with correction for multiple
comparisons. CMD indicates cerebral microdialysis; FiO2, fraction inspired oxygen (%); PbtO2, brain tissue oxygen partial pressure
(mm Hg). From Quintard et al,178 with permission.
www.jnsa.com |
109
J Neurosurg Anesthesiol
Exposure to sevourane was <1 hour. The primary outcome measure was performance on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at
5 years after randomization. Although primary outcome
data from this trial have not yet been released, the authors
reported the secondary outcome measurethat is, the
composite cognitive score of the Bayley Scales of Infant
and Toddler Development (ie, the Bayley III)230at 2
years after randomization. Briefly, the Bayley III assesses
infant and toddler development based on 5 major axes:
cognitive skills, communication skills, motor skills, social/
emotional behavior, and adaptive behavior. Scores from
each axis are compiled into a composite score that is
scaled such that the mean of a large random sample is 100
with a SD of 15. Outcome data were available from 238 of
363 children in the regional anesthesia group and 294 of
359 children in the general anesthesia group; missing data
were imputed. Overall, the composite scores at 2 years
were 98.6 14.2 and 98.2 14.7 in the regional
and general anesthesia groups, respectively (P not significant). Although additional outcome results from this
trial are still pending, these data preliminarily suggest that
sevoflurane does not result in overt neurotoxicity in young
children. However, because these data are limited to the
use of only 1 volatile anesthetic drug (ie, sevoflurane), and
children were exposed to that anesthetic for <1 hour, the
results of this research, though encouraging, may not be
generalizable to other anesthetic agents, multiple exposures to general anesthetics, or longer individual or
combined durations of general anesthesia and surgery.
Young children exposed to multiple general anesthetics at an early age were more likely to subsequently
manifest attention-decit hyperactivity syndrome.231 Using the National Health Insurance Research Database of
Taiwan, Ko et al232 assessed the relationship between
early exposure to general anesthesia and subsequent risk
for autism. The database used in this project contains
information from approximately 99% of the population
of Taiwan. Of the 114,435 children born in Taiwan between January 1, 2001 and December 31, 2007, and whose
data were in the database, 5197 received general anesthesia before the age of 2 years. Each study subject was
matched with 4 control subjects (those who did not receive general anesthesia before the age of 2 y) based on
sex, birth year, and birth month. The index date in the
control group was dened as the date that their matched
study subject received general anesthesia. No study subject had been diagnosed with autism before receiving
anesthesia, and control subjects were not diagnosed with
autism before their index date. The mean age of diagnosis
of autism was 4.04 1.80 years. Rates of autism were
0.96% and 0.89% in the study and control groups, respectively (P = 0.62). Although the rates of perinatal
medical complications, congenital anomalies, neurological diseases, and endocrine diseases were more common in the study cohort, and these factors were
associated with the diagnosis of autism, anesthesia exposure was still not associated with increased risk for
subsequent diagnosis of autism. Age at the time of rst
110 | www.jnsa.com
exposure was not associated with increased risk for autism. Further, the number of anesthetics was not associated with risk for autism.
It has been reported that up to 50% of children who
undergo anesthesia and surgery suer from negative behavioral changes afterward.233 These changes can involve increased anxiety, changes in eating or sleeping patterns, or
unusual fears. Stipic et al234 randomized 64 children having
tonsillectomy to receive general anesthesia with either sevourane and nitrous oxide or a propofol infusion. Sevourane
and propofol were titrated to maintain a BIS of 40 to 60
during the procedure. Patients in the propofol group received
an intravenous induction with propofol, whereas those in the
sevourane group received an inhalational induction with
sevourane. Postoperative behavior assessment was conducted with the Post-Hospitalization Behavior Questionnaire
before surgery, on postoperative days 1, 3, 7, and 14, and
again at 6 months following surgery. This questionnaire
quantied parental assessment of 6 axes: general anxiety,
separation anxiety, sleep patterns, eating disturbances, aggression, and apathy/withdrawal. Scores following surgery
were compared with presurgical scores. A score indicating
worsening of any axis was dened as a negative postoperative
behavioral change. As illustrated in Table 3, negative postoperative behavioral changes were common following surgery and anesthesia but were more common following
sevourane than propofol at every time point of assessment.
Further, simultaneous changes in all 6 axes were more
common in patients who received sevourane at all postoperative time points. The greatest dierence between groups
was noted in the separation anxiety axis, although this may
have been related to inhalation induction of anesthesia with
sevourane. Specically, it was implied in the methods that
all children had intravenous access obtained and intravenous
midazolam (a drug with anxiolytic properties) administered
(0.05 mg/kg) before induction of anesthesia. Inhalational induction of anesthesia without adequate amnesia may have
confounded the results.
Older patients having anesthesia and surgery are
at increased risk for postoperative delirium and cognitive dysfunction. Delirium refers to an acute confusional state that temporally uctuates. Hesse et al235
reported that prolonged procedures and preexisting
neurological comorbidities were risk factors for delirium in the recovery room. Kichloo et al236 found that
increased age, higher ASA physical status classication,
and preoperative depression were independent risk
factors for delirium. Punjasawadwong and Punjasawadwong237 reported a meta-analysis that discovered
that the use of BIS monitoring is associated with reduced delirium in elderly patients. It is unclear how
postoperative delirium contributes to long-term outcome. For example, Gottschalk et al238 recently reported that postoperative delirium following repair of
hip fracture in the elderly did not predict an increased
long-term risk of death.
Postoperative cognitive dysfunction refers to a decrease in cognitive abilities following anesthesia and surgery. It is a more static condition that appears to slowly
Copyright
J Neurosurg Anesthesiol
POD 1
POD 3
POD 7
POD 14
6 mo
postoperatively
49
48
41
29
26
Propofol
Group (n [%])
23
21
16
9
5
(72)
(66)
(52)
(28)
(16)
Sevourane Group
(n [%])
28
29
26
20
22
(88)
(91)
(84)
(65)
(69)
P
NS
0.016
0.007
0.004
< 0.001
Neuroanesthesiology Update
Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)244 randomized 1260
persons 60 to 77 years of age to either an accountable
lifestyle modication program (ie, improved diet, regular
exercise, cognitive training, and vascular risk factor
modication) or just general health advice. Subjects in the
treatment group had signicantly better postintervention
executive functioning skills and processing speed than
those who received general health advice at 24 months
after randomization. Recently, various animal models
have demonstrated an attenuation of anesthetic neurotoxicity (ie, decreased apoptosis, improved cognitive
function) by environmental enrichment.245,246 However,
the mechanism for this eect is unclear. Kawano et al212
assigned rats to one of 4 groups based on a 2 2 design:
(1) an environment with or without enrichment items and
(2) anesthesia with or without surgery. Environmental
enrichment items consisted of a maze that was changed
daily and an exercise wheel, and assignment to the environments was for 14 days before anesthesia exposure.
Surgery consisted of a standardized laparotomy followed
by small bowel manipulation for 3 minutes and closure of
the incision. Anesthesia consisted of 1.5% to 2% inspired
isourane, with ropivacaine inltration of the incision
restricted to the surgical group. Cognitive function was
assessed with the Novel Object Recognition Test that
assesses memory at 7 days following anesthesia (ie, normal rats spend more time exploring a novel object). The
experimental protocol was conducted with a group of
young (age 2 to 3 mo) and old (age 24 to 25 mo) rats,
separately. Additional sets of young and old rats underwent microglial harvesting from the hippocampus for
quantication of inammatory cytokine concentrations
(ie, tumor necrosis factor-a and interleukin-1-b). Cytokine harvesting was conducted 2 weeks before anesthesia
exposure, and rats were then placed into either enriched
or unenriched environments. A subset underwent microglial harvesting before anesthesia and surgery, with the
remaining animals having microglial harvesting at 7 days
following anesthesia and surgery. In young rats, neither
surgery nor environmental enrichment impacted memory
function or expression of inammatory cytokines in the
hippocampus. In older rats assigned to an unenriched
environment for 14 days followed by anesthesia and surgery, memory decits and increased expression of both
)
(
(
(
)]
)]
www.jnsa.com |
111
J Neurosurg Anesthesiol
PreCI (n = 96)
No PreCI (n = 204)
23/91 (25.3)
16.7-35.5
26/195 (13.3)
8.9-18.9
0.012
13/87 (14.9)
8.2-24.2
14/197 (7.1)
3.9-11.6
0.039
5/83 (9.4)
2.0-13.5
2/188 (1.1)
0.1-3.8
< 0.001
Data are presented as: number with POCD/number of subjects tested (%).
CI indicates condence interval; POCD, postoperative cognitive dysfunction;
PreCI, preexisting cognitive impairment.
From Silbert et al,241 with permission.
MONITORING
Recent reports of new neurological decits following
surgical procedures performed in the sitting position have
been attributed, in part, to cerebral hypoperfusion.254 This
hypoperfusion can result from inadequate systemic blood
pressure, possibly related to failure to correct for hydrostatic gradients between the brain and the site of blood
pressure measurement. In theory, ischemic brain injury
would be most likely when cerebral perfusion pressure falls
below the brains lower limit of autoregulation. Recently,
Laam et al255 hypothesized that cerebral autoregulation
may be impaired in patients having surgery in the sitting
position, further contributing to increased risk for hypoperfusion. A total of 218 patients having shoulder surgery
in the beach chair (n = 109) and lateral decubitus (n = 109)
positions underwent a standard set of neuropsychometric
112 | www.jnsa.com
J Neurosurg Anesthesiol
Neuroanesthesiology Update
Combined
(n = 56)
Propofol
(n = 29)
Desurane
(n = 27)
Beach Chair
FiO2 = 0.3,
EECO2 = 30 mm Hg
FiO2 = 0.3,
EECO2 = 30 mm Hg
FiO2 = 1.0,
EECO2 = 30 mm Hg
FiO2 = 1.0,
EECO2 = 45 mm Hg
FiO2 = 0.3,
ETEO2 = 45 mm Hg
68 12
61 12*
66 12*
75 12*
65 13*
67 13
59 13*
64 14*
74 12*
64 14*
69 11
62 10*
67 11*
76 11*
67 12*
a rate of 0.082%/minute. In anesthetized patients monitored with the FORE-SIGHT device, rSO2 of hemoglobin
decreased from 74% 5% in the supine position to
72% 4% (P-value not reported in manuscript) immediately following placement in the prone position, but
thereafter increased at a rate of 0.0314%/minute. No
anesthetized patient had a saturation decrease of >5% of
the supine value. In awake volunteers, the INVOS rSO2
of hemoglobin was 70% 3% at baseline, and there was
no change following placement in the prone position.
Thereafter, saturation increased by 0.179%/minute.
Indocyanine green is a uorescent dye commonly
used during intracranial vascular surgery and can cause a
false decrease in traditional pulse oximetry readings, but
its eects on cerebral oximetry are unknown.263 Yoo
et al264 conrmed a 0% to 4% decrease in hemoglobin
oxygen saturation by traditional pulse oximetry following
intravenous administration of indocyanine green, and
values returned to baseline in 2.9 1.4 minutes. However, there was a 6% to 20% increase in rSO2 of hemoglobin measured with an INVOS 5100B oximeter
(INVOS; Somanetics), and 12.1 3.8 minutes were required before values returned to baseline. These dierences are likely due to dierences in the wavelengths of
light and the algorithms used to determine oxygen saturation of hemoglobin between the standard pulse oximeter and the cerebral oximeter. Also of note, Sun et al265
reported that skin pigment coloration correlates with
rSO2 values when measured with an INVOS 5100C (Somanetics) device. Specically, presurgical baseline regional oximetry values were 53% 13% in African
Americans and 65% 12% in whites (P < 0.01).
Robot-assisted prostatectomy is generally performed
with the patient in the steep Trendelenburg position and
requires insuation of the abdominal cavity with carbon
dioxide gas. These 2 factors (ie, Trendelenburg position
and increased systemic carbon dioxide tension) can potentially increase intracranial pressure. Whiteley et al266
measured optic nerve sheath diameter with ultrasonography in 25 patients having robotic prostatectomy.
Optic nerve sheath diameter can be used as a surrogate
metric of ICP and is responsive to physiological changes
www.jnsa.com |
113
J Neurosurg Anesthesiol
114 | www.jnsa.com
J Neurosurg Anesthesiol
distribution of the median and tibial nerves and recorded from the scalp. MEPs were induced by electrical
stimulation of the scalp and measured in the belly of the
thenar and abductor halluces muscles. At no point was
there a dierence in MEP, SSEP, or visual evoked potential waveform amplitude or latency between groups
during the study. Therefore, dexmedetomidine was
found to have minimal, if any, eect on evoked potential waveforms during propofol and remifentanil
anesthesia. These ndings may not be directly applicable to children or those with preexisting neurological
decits.
Some patients, such as children or those with developmental delay, may not be able to tolerate having a diagnostic EEG awake and require sedation. Unfortunately,
many drugs that are commonly used for sedation, such as
barbiturates, propofol, and benzodiazepines, can profoundly aect not only the frequency and amplitude
properties of the EEG but can also attenuate epileptiform
and epileptic activity. Chloral hydrate is a commonly used
sedative in this setting because it is reported to have less of
a suppressant eect on epileptiform activity than other
anesthetic drugs.292,293 Fernandes et al294 compared EEGs
obtained in patients age 12 to 40 years who initially received an EEG during chloral hydrate sedation followed
by a second EEG at a dierent time during dexmedetomidine sedation. Patients received chloral hydrate (50 mg/
kg) orally with an additional 25 mg/kg given for
inadequate sedation. Dexmedetomidine was administered
as an intravenous bolus of 1 mg/kg over 10 minutes followed by an infusion of 0.2 to 0.7 mg/kg/h. Sedation was
titrated to have the patient either very sleepy with a tendency to go to sleep if not stimulated versus continually
sleeping with minimal, if any, response to stimulation. The
frequency and characteristics of sleep spindles were similar
between groups. Compared with the EEG during chloral
hydrate, dexmedetomidine was associated with increased
power in the d and y ranges and less power in the a and b
ranges. The authors commented that dexmedetomidine did
not grossly change the presence and properties of epileptiform activity, but they did not quantify this eect.
Further study will be required to determine whether use of
dexmedetomidine for sedation to obtain EEGs impairs the
diagnostic ability of this test for epilepsy.
For readers interested in additional information on
central nervous system monitoring, we refer you to a review by Hiles et al.295 The review focuses on noninvasive
technologies and emphasizes technologies that can be used
in remote environments including mainstream aviation,
high-altitude ascension, and spaceight. The authors also
discuss ultrasound-based techniques such as time-of-ight
ultrasonography, transcranial Doppler sonography, and
ocular ultrasound. Spectroscopic techniques including
near-infrared spectroscopy and diuse-correlation spectroscopy are discussed. Finally, they include ocular and
otic techniques such as pupillometry, visual evoked potentials, ophthalmodynamometry, tympanic membrane
displacement, and distortion-product otoacoustic emissions.
Copyright
Neuroanesthesiology Update
CONCLUSIONS
Our synopsis and speculative synthesis of the 2015
literature is intended to provide an overview for anyone
involved in the care of neurosurgical patients or involved
in basic or translational neuroscience research. For interested readers, we refer you to some of our more recent
annual reviews of the neuroanesthesia literature from
prior years.296,297
REFERENCES
1. Mathews L, Kla KM, Marolen KN, et al. Measuring and
improving first case on-time starts and analysis of factors
predicting delay in neurosurgical operating rooms. J Neurosurg
Anesthesiol. 2015;27:203208.
2. Arulvelan A, Gayatri P, Smita V, et al. A retrospective analysis of
stridor after vestibular schwannoma surgery. J Neurosurg Anesthesiol. 2014;26:1721.
3. Busl KM, Ouyang B, Boland TA, et al. Prolonged mechanical
ventilation is associated with pulmonary complications, increased
length of stay, and unfavorable discharge destination among
patients with subdural hematoma. J Neurosurg Anesthesiol. 2015;
27:3136.
4. Flexman AM, Merriman B, Griesdale DE, et al. Infratentorial
neurosurgery is an independent risk factor for respiratory failure
and death in patients undergoing intracranial tumor resection.
J Neurosurg Anesthesiol. 2014;26:198204.
5. Jeon YT, Hwang JW, Lim YJ, et al. Effect of tracheostomy
timing on clinical outcome in neurosurgical patients:
early versus late tracheostomy. J Neurosurg Anesthesiol. 2014;26:
2226.
6. Hooda B. Retrospective study of incidence and predictors of
postoperative pulmonary complications in adults undergoing
surgery for posterior fossa tumours. J Neurosurg Anesthesiol. 2014;
26:507508.
7. Shalev D, Kamel H. Risk of reintubation in neurosurgical patients.
Neurocrit Care. 2015;22:1519.
8. Bebawy JF, Houston CC, Kosky JL, et al. Nicardipine is superior to
esmolol for the management of postcraniotomy emergence hypertension:
a randomized open-label study. Anesth Analg. 2015;120:186192.
9. Jian M, Li X, Wang A, et al. Flurbiprofen and hypertension but not
hydroxyethyl starch are associated with post-craniotomy intracranial
haematoma requiring surgery. Br J Anaesth. 2014;113:832839.
10. Luthra A, Prabhakar H, Rath GP, et al. Alleviating stress response
to tracheal extubation in neurosurgical patients: a comparative
study of two infusion doses of dexmedetomidine. J Neurosurg
Anesthesiol. 2015;27:419.
11. Carron M, Veronese S, Gomiero W, et al. Hemodynamic and
hormonal stress responses to endotracheal tube and ProSeal
Laryngeal Mask Airway for laparoscopic gastric banding.
Anesthesiology. 2012;117:309320.
12. Perello-Cerda L, Fabregas N, Lopez AM, et al. ProSeal laryngeal
mask airway attenuates systemic and cerebral hemodynamic
response during awakening of neurosurgical patients: a randomized clinical trial. J Neurosurg Anesthesiol. 2015;27:194202.
13. Brimacombe JR, Wenzel V, Keller C. The proseal laryngeal mask
airway in prone patients: a retrospective audit of 245 patients.
Anaesth Intensive Care. 2007;35:222225.
14. Kang F, Li J, Chai X, et al. Comparison of the I-gel laryngeal mask
airway with the LMA-supreme for airway management in patients
undergoing elective lumbar vertebral surgery. J Neurosurg Anesthesiol. 2015;27:3741.
15. Klug W, Reiterer C, Bukaty A, et al. A new method of airway
management in patients undergoing Gasserian ganglion thermal
coagulation: preliminary results. J Neurosurg Anesthesiol. 2015;27:
252256.
16. Han DW, Shim YH, Shin CS, et al. Estimation of the length of the
nares-vocal cord. Anesth Analg. 2005;100:15331535.
17. Bergenheim AT, Asplund P, Linderoth B. Percutaneous retrogasserian balloon compression for trigeminal neuralgia: review of
www.jnsa.com |
115
J Neurosurg Anesthesiol
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
116 | www.jnsa.com
Copyright
J Neurosurg Anesthesiol
Copyright
Neuroanesthesiology Update
www.jnsa.com |
117
J Neurosurg Anesthesiol
118 | www.jnsa.com
122. Muir KW, Lees KR, Ford I, et al. Magnesium for acute stroke
(Intravenous Magnesium Efficacy in Stroke trial): randomised
controlled trial. Lancet. 2004;363:439445.
123. Saver JL, Starkman S, Eckstein M, et al. Prehospital use of
magnesium sulfate as neuroprotection in acute stroke. N Engl J
Med. 2015;372:528536.
124. Cheungpasitporn W, Thongprayoon C, Qian Q. Dysmagnesemia
in hospitalized patients: prevalence and prognostic importance.
Mayo Clin Proc. 2015;90:10011010.
125. Dorhout Mees SM, Van den Bergh WM, Algra A, et al. Achieved
serum magnesium concentrations and occurrence of delayed
cerebral ischaemia and poor outcome in aneurysmal subarachnoid
haemorrhage. J Neurol Neurosurg Psychiatry. 2007;78:729731.
126. Walsh SB, Zdebik AA, Unwin RJ. Magnesium: the disregarded
cation. Mayo Clin Proc. 2015;90:993995.
127. Chamorro A, Meisel A, Planas AM, et al. The immunology of
acute stroke. Nat Rev Neurol. 2012;8:401410.
128. Westendorp WF, Vermeij JD, Zock E, et al. The Preventive
Antibiotics in Stroke Study (PASS): a pragmatic randomised openlabel masked endpoint clinical trial. Lancet. 2015;385:15191526.
129. Bath PM, Woodhouse L, Scutt P, et al. Efficacy of nitric oxide,
with or without continuing antihypertensive treatment, for
management of high blood pressure in acute stroke (ENOS): a
partial-factorial randomised controlled trial. Lancet. 2015;385:
617628.
130. Ho AL, Lin N, Frerichs KU, et al. Smoking and intracranial
aneurysm morphology. Neurosurgery. 2015;77:5966.
131. Uchida K, Yasunaga H, Sumitani M, et al. Effects of remifentanil
on in-hospital mortality and length of stay following clipping of
intracranial aneurysm: a propensity score-matched analysis.
J Neurosurg Anesthesiol. 2014;26:291298.
132. Eisen SH, Hindman BJ, Bayman EO, et al. Elective endovascular
treatment of unruptured intracranial aneurysms: a management
case series of patient outcomes after institutional change to admit
patients principally to postanesthesia care unit rather than to
intensive care. Anesth Analg. 2015;121:188197.
133. Goettel N, Chui J, Venkatraghavan L, et al. Day surgery
craniotomy for unruptured cerebral aneurysms: a single center
experience. J Neurosurg Anesthesiol. 2014;26:6064.
134. Bederson JB, Connolly ES Jr, Batjer HH, et al. Guidelines for the
management of aneurysmal subarachnoid hemorrhage: a statement
for healthcare professionals from a special writing group of the
Stroke Council, American Heart Association. Stroke. 2009;40:
9941025.
135. Diringer MN, Bleck TP, Claude Hemphill J III, et al. Critical care
management of patients following aneurysmal subarachnoid
hemorrhage: recommendations from the Neurocritical Care
Societys Multidisciplinary Consensus Conference. Neurocrit Care.
2011;15:211240.
136. Steiner T, Juvela S, Unterberg A, et al. European Stroke
Organization guidelines for the management of intracranial
aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis. 2013;
35:93112.
137. Velly LJ, Bilotta F, Fabregas N, et al. Anaesthetic and ICU
management of aneurysmal subarachnoid haemorrhage: a survey
of European practice. Eur J Anaesthesiol. 2015;32:168176.
138. Kassell NF, Torner JC, Jane JA, et al. The international
cooperative study on the timing of aneurysm surgery. Part 2:
surgical results. J Neurosurg. 1990;73:3747.
139. Nickols G, Taylor CJ, Shephen T, et al. The timeing of acute
endovascular treatment and neurological ourcome in poor grade
aneurysmal subarachnoid hemorrhage patients. J Neurosurg
Anesthesiol. 2014;26:429.
140. Mutoh T, Kazumata K, Yokoyama Y, et al. Comparison of
postoperative volume status and hemodynamics between surgical
clipping and endovascular coiling in patients after subarachnoid
hemorrhage. J Neurosurg Anesthesiol. 2015;27:715.
141. Kassell NF, Peerless SJ, Durward QJ, et al. Treatment of ischemic
deficits from vasospasm with intravascular volume expansion and
induced arterial hypertension. Neurosurgery. 1982;11:337343.
Copyright
J Neurosurg Anesthesiol
Copyright
Neuroanesthesiology Update
www.jnsa.com |
119
J Neurosurg Anesthesiol
184. Roberts DJ, Hall RI, Kramer AH, et al. Sedation for critically
ill adults with severe traumatic brain injury: a systematic review
of randomized controlled trials. Crit Care Med. 2011;39:27432751.
185. Hertle DN, Santos E, Hagenston AM, et al. Cerebral glucose
metabolism and sedation in brain-injured patients: a microdialysis
study. J Neurosurg Anesthesiol. 2015;27:187193.
186. Nicholl J, LaFrance WC Jr. Neuropsychiatric sequelae of
traumatic brain injury. Semin Neurol. 2009;29:247255.
187. Chirumamilla S, Sun D, Bullock MR, et al. Traumatic brain injury
induced cell proliferation in the adult mammalian central nervous
system. J Neurotrauma. 2002;19:693703.
188. Dash PK, Mach SA, Moore AN. Enhanced neurogenesis in the
rodent hippocampus following traumatic brain injury. J Neurosci
Res. 2001;63:313319.
189. Williams S, Raghupathi R, MacKinnon MA, et al. In situ DNA
fragmentation occurs in white matter up to 12 months after head
injury in man. Acta Neuropathol. 2001;102:581590.
190. Blanchard J, Bolognin S, Chohan MO, et al. Rescue of synaptic
failure and alleviation of learning and memory impairments in a
trisomic mouse model of down syndrome. J Neuropathol Exp
Neurol. 2011;70:10701079.
191. Blanchard J, Wanka L, Tung YC, et al. Pharmacologic reversal of
neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Abeta and tau pathologies in 3xTg-AD
mice. Acta Neuropathol. 2010;120:605621.
192. Chohan MO, Li B, Blanchard J, et al. Enhancement of dentate
gyrus neurogenesis, dendritic and synaptic plasticity and memory
by a neurotrophic peptide. Neurobiol Aging. 2011;32:14201434.
193. Chohan MO, Bragina O, Kazim SF, et al. Enhancement of
neurogenesis and memory by a neurotrophic peptide in mild to
moderate traumatic brain injury. Neurosurgery. 2015;76:201214.
194. Wijayatilake DS, Sherren PB, Jigajinni SV. Systemic complications
of traumatic brain injury. Curr Opin Anaesthesiol. 2015;28:525531.
195. Wijayatilake DS, Jigajinni SV, Sherren PB. Traumatic brain injury:
physiological targets for clinical practice in the prehospital setting
and on the Neuro-ICU. Curr Opin Anaesthesiol. 2015;28:517524.
196. Makaryus R, Lee H, Feng T, et al. Brain maturation in neonatal
rodents is impeded by sevoflurane anesthesia. Anesthesiology.
2015;123:557568.
197. Yan J, Jiang H. Dual effects of ketamine: neurotoxicity versus
neuroprotection in anesthesia for the developing brain. J Neurosurg
Anesthesiol. 2014;26:155160.
198. Yu X, Liu Y, Bo S, et al. Effects of sevoflurane on learning,
memory, and expression of pERK1/2 in hippocampus in neonatal
rats. Acta Anaesthesiol Scand. 2015;59:7884.
199. Huang L, Yang G. Repeated exposure to ketamine-xylazine during
early development impairs motor learning-dependent dendritic
spine plasticity in adulthood. Anesthesiology. 2015;122:821831.
200. Wang YL, Chen X, Wang ZP. Detrimental effects of postnatal
exposure to propofol on memory and hippocampal LTP in mice.
Brain Res. 2015;1622:321327.
201. Jian M, Pearn M, Egawa J, et al. Inhibition of RhoA activity with
TAT-C3 attenuates propofol mediated toxicity. J Neurosurg
Anesthesiol. 2015;27:399.
202. Lin D, Liu J, Hu Z, et al. Brain microRNA profiling after neonatal
sevoflurane treatment. J Neurosurg Anesthesiol. 2015;27:400402.
203. Twaroski DM, Yan Y, Zaja I, et al. Altered mitochondrial
dynamics contributes to propofol-induced cell death in human
stem cell-derived neurons. Anesthesiology. 2015;123:10671083.
204. Horiguchi T, Masaki Y, Kawamura K, et al. Ultrastructural
changes in the brain cells after discontinuation of sevoflurane
anesthesia in rats. J Neurosurg Anesthesiol. 2015;27:369.
205. Hata K, Ajima T, Takemura Y, et al. Sevoflurane exposure induces
spatial memory impairment in early neonatal mice. J Neurosurg
Anesthesiol. 2015;27:369.
206. Lee B, Sall JW. Effect of early repeated anesthetic exposure on
long-term cognition. J Neurosurg Anesthesiol. 2015;27:399.
207. Xie S, An L. The effect of sevoflurane on neuron apoptosis,
GABAA Ra1/GABAA Ra2 in hippocampus and learning ability of
neonatal rats. J Neurosurg Anesthesiol. 2015;27:403404.
120 | www.jnsa.com
Copyright
J Neurosurg Anesthesiol
230.
231.
232.
233.
234.
235.
236.
237.
238.
239.
240.
241.
242.
243.
244.
245.
246.
247.
248.
249.
Copyright
Neuroanesthesiology Update
www.jnsa.com |
121
J Neurosurg Anesthesiol
269.
270.
271.
272.
273.
274.
275.
276.
277.
278.
279.
280.
281.
282.
283.
122 | www.jnsa.com
284.
285.
286.
287.
288.
289.
290.
291.
292.
293.
294.
295.
296.
297.
Copyright