Novel approaches to_spinal_cord_protection_during.15

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CURRENT
OPINION Novel approaches to spinal cord protection during
thoracoabdominal aortic interventions
John G.T. Augoustidesa
, Marc E. Stoneb
, and Benjamin Drengerc
Purpose of review
Spinal cord ischemia after thoracoabdominal aortic interventions is a devastating complication because it
significantly worsens the perioperative morbidity and mortality. Long-term outcome is also affected because
of medical complications which are directly related to the neural deficits. Paraplegia has significant
medical, social, and financial aspects. Limited mobility, the need for assistance in activities of daily living,
makes paraplegia an important target for prevention. An understanding of spinal cord blood supply, risk
factors for spinal ischemia, and strategies for spinal cord rescue in this setting can help minimize the
negative outcome effects of this important complication.
Recent findings
The vascular supply of the spinal cord is via an extensive collateral arterial network with multiple auxiliary
arterial supplies. Risk factors for spinal cord ischemia include extensive aortic repair, prior aortic repair,
spinal cord malperfusion on clinical presentation, systemic hypotension, acute anemia, prolonged aortic
clamping, and vascular steal. Spinal rescue strategies include systemic hypothermia, endovascular aortic
repair, permissive systemic hypertension, cerebrospinal fluid drainage, pharmacologic neuroprotection,
and intensive neuromonitoring.
Summary
The progression of spinal cord ischemia after thoracoabdominal aortic interventions can frequently be
arrested before irreversible infarction results. This spinal cord rescue depends on the early detection and
immediate multimodal intervention to maximize spinal cord oxygen supply. The devastating outcomes
associated with spinal infarction in this setting offset the risks and knowledge gaps currently associated with
contemporary interventions.
Keywords
cerebrospinal fluid drainage, collateral arterial network, evoked potentials, hypothermia, spinal cord ischemia
INTRODUCTION
Spinal cord protection remains clinically important
after thoracoabdominal aortic interventions (TAAIs)
because spinal cord ischemia is still common and
significantly worsens the perioperative morbidity
and mortality [1,2,3
&
]. Spinal cord ischemia is man-
ifested in the conscious patient by the development
of lower extremity weakness or during surgery
by the attenuation of spinal cord signals with
monitoring of somatosensory-evoked potentials
and motor-evoked potentials [4,5,6
&&
]. The aortic
repair techniques in the contemporary era can be
open, endovascular, or hybrid. Total endovascular
repair may include the use of fenestrated or
branched endovascular stent components to not
only exclude the aneurysm, but also to preserve
aortic branch perfusion. Hybrid TAAIs typically
involve nonfenestrated endovascular repair of
diseased aorta combined with open surgical
transposition of aortic branches to preserve critical
organ perfusion [7,8]. This review is focused on the
recent approaches to protect the spinal cord during
TAAI from an anesthesiology perspective. It will
highlight the risk factors for spinal cord ischemia
and the principal spinal cord preservation strategies.
a
Department of Anesthesiology and Critical Care, Perelman School of
Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,
b
Department of Anesthesiology, Icahn School of Medicine, Mount Sinai
Medical Center, New York, New York, USA and c
Department of Anes-
thesiology and Critical Care Medicine, Hadassah-Hebrew University
Medical Centers, Jerusalem, Israel
Correspondence to John G.T. Augoustides, MD, FASE, FAHA, Associate
Professor, Cardiothoracic Section, Anesthesiology and Critical Care,
Dulles 680, HUP, 3400 Spruce Street, Philadelphia, PA 19104-4283,
USA. Tel: +1 215 662 7631; fax: +1 215 349 8133; e-mail: yiandoc
@hotmail.com
Curr Opin Anesthesiol 2014, 27:98–105
DOI:10.1097/ACO.0000000000000033
www.co-anesthesiology.com Volume 27 Number 1 February 2014
REVIEW

Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.
RISK FACTORS FOR SPINAL CORD
ISCHEMIA: THE IMPORTANCE OF THE
SPINAL COLLATERAL ARTERIAL
NETWORK
The cause of spinal cord ischemia after TAAI is a net
oxygen debt in the spinal cord, where neural oxygen
supply is hampered by the surgical intervention.
Spinal cord protection after TAAI depends on an
understanding of the risk factors for spinal cord
ischemia, summarized in Table 1. An important
mechanism underlying these risk factors is the com-
promise of the spinal collateral arterial network
(SCAN), as outlined in the comments in Table 1.
The SCAN concept has resulted in large part from
the bench and bedside research by Griepp and col-
leagues [9,10].
In 1882, Adamkiewicz described the spinal cord
vascular plexus of the anterior and posterior spinal
arteries with augmentation from cephalic, central,
and caudal input [5,9,10]. Griepp et al. showed that
perfusion in these spinal arteries is supported by
complex and intertwined collateral network, with
cephalic contribution to the SCAN from the
brachiocephalic arteries and with significant
contribution from the vertebral arteries. The central
arterial input to the SCAN is from multiple seg-
mental aortic branches such as the intercostal
and lumbar arteries. This central arterial supply to
the SCAN is scarcely dispersed in the lower thoracic
area, but frequently includes a large arterial branch
at the level of the lower thoracic called the artery
of Adamkiewicz or the arteria radicularis magna.
This augmented supply from this large segmental
artery is vital, given the small diameter of the
anterior spinal artery in the mid-to-lower thoracic
area (T8 to L1). The caudal arterial supply to the
SCAN is from the internal iliac arteries and
their branches. The SCAN concept explains that
spinal cord perfusion stems from multiple intercon-
nected sources that require adequate perfusion
pressure and vascular tone throughout the arterial
network.
STRATEGIES FOR SPINAL CORD
PROTECTION
The contemporary strategies for perioperative spinal
cord protection can frequently be understood as
therapeutic consequences of the SCAN concept.
Although they are summarized in Table 2, they will
now be more fully explored in this section.
Deep hypothermia
Deep hypothermia for spinal cord protection is an
established technique in TAAI as it minimizes the
neural oxygen demand during aortic reconstruction
when oxygen delivery is compromised [11

,12

].
The definition of deep hypothermia by the recent
expert consensus is a systemic temperature range
of 14.1–20.0 degrees Celsius, ideally measured at
the nasopharynx [13

]. In addition to spinal cord
protection, deep hypothermic circulatory arrest
(DHCA) offers multiple advantages in open TAAI
such as minimal dissection of periaortic tissues,
elimination of the requirement for sequential aortic
clamping, easy access to the aortic arch, and excel-
lent visceral organ protection [11

,12

]. In a recent
single-center evaluation of open thoracoabdominal
aneurysm repair (n ¼ 243: Crawford extent I 26%;
Crawford extent II 40%; Crawford extent III 34%)
utilizing DHCA, the incidence of spinal cord ische-
mia was 5.3% (13 patients: nine with paraplegia and
four with paraparesis) [14]. Emergency surgery was
significantly associated with spinal cord ischemia
compared with elective surgery (16.7 vs. 3.9%;
P ¼ 0.04) [14]. Fehrenbacher and colleagues have
also recently demonstrated in a similar large con-
temporary series (n ¼ 343) with DHCA that the
incidence of spinal cord ischemia was 1.1–3.2%,
depending on the aortic disease [15,16]. These data
demonstrate that experienced perioperative teams
can achieve excellent spinal cord protection in
extensive open TAAI with DHCA.
KEY POINTS
Spinal cord ischemia still occurs after
thoracoabdominal aortic interventions, regardless of the
technique or aortic disease. It is considered a
devastating perioperative complication.
Spinal cord ischemia occurs when oxygen supply is
insufficient to meet the neural oxygen demand.
The detection of spinal cord ischemia relies on
neuromonitoring with evoked potentials in the
anesthetized patient and on neurologic examination in
the awake patient.
The vascular supply to the spinal cord is via the anterior
and posterior spinal arteries, that are supported by a
collateral arterial network, which has cephalic, central,
and caudal inputs.
The risk factors and therapeutic interventions for spinal
cord ischemia after thoracoabdominal aortic
interventions can largely be understood in terms of their
effects on the spinal collateral arterial network and
spinal cord perfusion pressure.
Rescue from spinal cord ischemia in thoracoabdominal
aortic interventions is frequently possible with a
multimodal protocol.
Novel approaches to spinal cord protection Augoustides et al.
0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams Wilkins www.co-anesthesiology.com 99

Thoracic endovascular aortic repair
Extensive meta-analysis has suggested that across
diverse aortic diseases, thoracic endovascular aortic
repair (TEVAR), per se, compared with open repair
significantly decreases the risk of spinal cord ische-
mia in TAAI [5,7,8]. A recent analysis of TEVAR vs.
open repair in DeBakey Type III chronic dissections
(n ¼ 89) from two experienced medical centers dem-
onstrated that TEVAR significantly reduced the risks
of perioperative mortality (0 vs. 10.3%) and spinal
cord ischemia (0 vs. 12.1%) [17]. Contemporary
meta-analysis of hybrid TAAI has demonstrated in
very high-risk patients (n ¼ 660: 19 studies) that
hybrid techniques may reduce mortality and spinal
cord ischemia, although the investigators con-
cluded that further high-quality trials are indicated
to clarify the extent of these outcome advantages
[18].
A large single-center analysis of TAAI (n ¼ 406)
over 11 years demonstrated an unexpectedly low
incidence of spinal cord ischemia, namely 2.7%
with a permanent neurological deficit of only
1.5% [19

]. Independent risk factors for spinal cord
ischemia in this series were consistent with Table 1:
previous abdominal aortic aneurysm repair [odds
ratio 4.8 (OR); 95% confidence interval (CI) 1.4–
17.2; P ¼ 0.026], extensive coverage of the descend-
ing thoracic aorta (OR 3.6; 95% CI 1.1–12.3;
P ¼ 0.038), and implantation of thoracoabdominal
branched or fenestrated grafts (OR 9.5; 95% CI 1.2–
50.6; P ¼ 0.032) [19

]. The investigators postulated
that the extensive arterial network, the SCAN, as
explained by Griepp and colleagues, is the likely
explanation for the low incidence of spinal cord
incidence in their reported TEVAR experience.
Although TEVAR results in coverage of central spi-
nal segmental arterial supply, back bleeding is pre-
vented, and in this fashion prevents vascular steal in
that part of the vascular network. Furthermore, the
investigators pointed out that collateral perfusion
from the paravertebral muscle compartment will
also augment spinal segmental perfusion in the
Table 1. Risk factors for spinal cord ischemia during thoracoabdominal aortic interventions
Risk factors Comment
Complicated aortic dissection with visceral malperfusion,
e.g., acute type B dissection
In acute complicated aortic dissection, there may be spinal cord
ischemia, renal and intestinal ischemia, because of regional
malperfusion due to aortic branch occlusion or exclusion from the
dissection process.
Total extent of thoracoabdominal repair, e.g., Crawford
Extent II aneurysm repair has a very high risk of spinal cord
compromise
The risk of spinal cord ischemia increases with the extent of aortic
repair because of greater loss of segmental arterial spinal cord
supply.
Prior thoracoabdominal aortic segment repair, e.g., open
repair of abdominal aortic aneurysm; endovascular repair
of the descending thoracic aorta
Prior aortic repair aggravates the risk of spinal cord ischemia
because of the loss of spinal cord arterial segmental supply
from the prior procedure. In this setting, the spinal cord has
compromised reserve of its collateral arterial network.
Extent of preservation of spinal segmental arterial supply,
e.g., intercostals arteries; lumbar arteries
The risk of spinal cord ischemia may be reduced if fenestrated
endograft is used, or in open aortic repair if intercostal arteries
are reimplanted into the aortic graft
Duration of aortic clamping In the absence of distal aortic perfusion, the duration of aortic
clamping to allow open aortic replacement often correlated with
the duration of spinal cord hypoperfusion and hence ischemia.
Distal aortic perfusion techniques will not completely mitigate the
risk of spinal cord ischemia.
Acute anemia Significant acute anemia is typically associated with severe bleed-
ing. Acute anemia aggravates spinal cord ischemia by impairing
oxygen delivery as a consequence of low hemoglobin mass.
Systemic hypotension Hypotension or circulatory collapse significantly compromises spinal
cord perfusion and thus may precipitate spinal cord ischemia from
decreased oxygen delivery.
Systemic vasodilation with vascular steal Vasodilators such as sodium nitroprusside have been utilized for
control of hypertension associated with aortic clamping. The
systemic vasodilation resulted in vascular steal, compromising
spinal perfusion pressure to precipitate spinal cord ischemia. Back
bleeding from open branches into the surgical field in open repair
will also cause the steal phenomenon.
Adapted with permission from [5] (no copyright required).
Cardiovascular anesthesia
100 www.co-anesthesiology.com Volume 27 Number 1 February 2014

TEVAR segment. This muscle compartment is typi-
cally perfused from the second dorsal branch of the
spinal segmental artery, and thus provides blood
supply to the segmental arterial branches at their
aortic origins where the TEVAR procedure was per-
formed [9,19

,20]. Given the very low incidence of
spinal cord ischemia over time in their series, the
investigators gradually abandoned routine utiliz-
ation of cerebrospinal fluid (CSF) drainage in their
TEVAR practice, a principle that will be discussed
further in the subsequent section of this article
[19

]. Given the beneficial effects of TEVAR on
morbidity and mortality in TAAI, it is likely that
this therapeutic approach will significantly expand
in the near future.
Maintenance of spinal cord perfusion
pressure: the importance of permissive
hypertension
Spinal cord perfusion pressure is defined as the
difference between systemic mean arterial pressure
and CSF pressure or right atrial pressure whichever is
greater [2,3

,4,5]. Consequently, any increase in
right atrial pressure to pressures higher than CSF
pressure will decrease the spinal cord perfusion
pressure. Raised right atrial pressure may result from
increased preload and increases in intrathoracic
pressure because of positive end-expiratory pressure.
Furthermore, if mean arterial pressure is elevated,
there will be a higher spinal cord perfusion pressure
and enhanced perfusion of the spinal cord through
the SCAN. This principle is central in the perioper-
ative management of patients undergoing TAAI to
preserve spinal cord perfusion and protect against
spinal cord ischemia. An important tenet of modern
spinal cord protection during TAAI (whether open
or endovascular) includes intentionally maintain-
ing the perioperative mean arterial blood pressure in
the high physiologic range, namely 80–100 mmHg
[21,22

].
Maintenance of high pressure in the collateral
spinal network for at least 24–48 h postoperatively
(or longer if there are apparent neurological deficits)
is important to the success of a spinal cord protec-
tion strategy, as progressive postoperative remodel-
ing of the SCAN has been demonstrated within 48 h
[9,20]. These acute adaptations in the SCAN include
increases in the diameter of the anterior spinal
artery and dilation of the epidural arterial network
within 24 h, and a realignment of the arterioles
parallel to the spinal cord by 5 days postoperatively
[9,20]. These adaptations in the SCAN allow acute
Table 2. Spinal cord protection strategies during thoracoabdominal aortic interventions
Risk factors Comment
Systemic hypothermia, e.g., deep hypothermic circulatory
arrest; moderate hypothermia with left heart bypass; mild
hypothermia with native circulation
Hypothermia reduces spinal oxygen demand and thus extends its
tolerance of limited oxygen supply. The aortic repair can be
conducted under deep hypothermia with circulatory arrest,
moderate hypothermia with circulatory support or mild
hypothermia with native circulation. Permissive mild hypothermia
should be induced with cautious to avoid the development of
arrhythmias. Deep hypothermia maximizes spinal cord protection
from cooling because of maximal suppression of neural
metabolism and hence minimizes oxygen demand.
Thoracoabdominal endovascular repair, including hybrid
techniques, e.g., endovascular stenting with fenestrated
or branched grafts; endovascular stenting with open
debranching procedures
Endovascular aortic repair lowers the risk of spinal cord ischemia
because of beneficial effects on the spinal collateral arterial
network. These benefits may be further enhanced if the extensive
aortic procedure can be staged.
Systemic hypertension, e.g., maintaining the mean arterial
pressure between 80 and 100 mmHg with titrated
intravenous norepinephrine infusion
Permissive systemic hypertension increases spinal cord perfusion
pressure. The technique should be applied both, during surgery
and on arrival to the intensive care unit. It is important during this
therapy to monitor for adequate cardiac output and bleeding from
disrupted suture lines.
Cerebrospinal fluid drainage (CSF), e.g., lumbar
subarachnoid catheter
Drainage of CSF increases spinal cord perfusion pressure. The safe
conduct of this intervention is essential to minimize serious
complications.
Pharmacologic neuroprotection These drugs increase neural tolerance of ischemia. The supporting
evidence is weak at best. Options include steroids, papaverine,
lidocaine, magnesium and minocycline.
Intensive neuromonitoring e.g.,. neurologic examination;
somatosensory-evoked potentials; motor-evoked potentials
Early detection of spinal cord ischemia is a clinical emergency. A
spinal rescue protocol should be urgently implemented in order to
recover spinal cord function.
Adapted with permission from [5] (no copyright required).

expansion of its capacity for enhanced spinal cord
perfusion. Permissive perioperative systemic hyper-
tension augments spinal cord perfusion after
TAAI, giving the SCAN the critical time to expand
capacity to compensate for the loss of segmental
arterial input resulting from the aortic repair
[19

,20,21,22

,23]. This strategy acts as part of a
bridge to recovery of the SCAN in the perioperative
period.
Drainage of cerebrospinal fluid
Perfusion pressurization of the SCAN is often insuf-
ficient to fully protect the spinal cord and prevent
paraplegia. Perioperative drainage of CSF to maxi-
mize spinal cord perfusion pressure (by minimizing
the resistance to afferent spinal cord blood supply) is
typical in modern TAAI. The 2010 American Heart
Association guidelines strongly recommend CSF
drainage (Class I, Level B evidence) in TAAI with
high risk of spinal cord ischemic injury [23].
In practice, although CSF drainage is primarily
utilized in high-risk patients, the final decision
depends on the team discussion and institutional
practice. Proactive CSF drainage as a routine part of a
perioperative protocol in TAAI with TEVAR has
recently been demonstrated in a single-center study
(n ¼ 94, 2005–2012) to be very effective with a 1.1%
incidence of spinal cord ischemia [24]. A second
approach, namely selective CSF drainage for post-
operative symptomatic spinal cord ischemia after
TEVAR, was associated with a 1.4% rate of perma-
nent spinal cord ischemia [25]. A third approach,
namely selective preoperative CSF drainage in high-
risk TEVAR patients, was evaluated in a recent large
single-center series (n ¼ 381, 2002–2012) [26]. The
incidences of permanent and temporary spinal cord
ischemia in this series were 1.8 and 4.7%, respect-
ively [26]. A single-center analysis of spinal cord
ischemia after TEVAR (n ¼ 424, 2002–2010) again
confirmed the low incidence of 2.8% with a 75%
rate of complete recovery, with early diagnosis and
prompt institution of permissive hypertension
alone or with CSF drainage [26]. In multivariate
analysis, chronic renal insufficiency was the only
independent predictor of spinal cord ischemia (OR
4.39; 95% CI 1.2–16; P ¼ 0.029) [26]. Further trials
are required to confirm renal dysfunction as a pre-
dictor for spinal cord ischemia after endovascular
TAAI.
A systematic review (n ¼ 4936, 46 studies)
recently evaluated whether preoperative CSF drain-
age in TEVAR reduces the risk of spinal cord ische-
mia [27]. The incidence of spinal cord ischemia in
this meta-analysis was 3.89% (95% CI 2.95–4.95%),
with no clear reductions evident with routine pre-
operative drainage, selective preoperative drainage,
or no preoperative drainage [27]. An updated
Cochrane meta-analysis evaluated CSF drainage in
open TAAI for aortic aneurysm (n ¼ 287, three
randomized controlled trials before 2005) [28

].
The overall benefit of CSF drainage in this limited
dataset was an 80% reduction in the relative risk of
spinal cord ischemia. A meta-analysis demonstrated
an OR for CSF drainage of 0.48 (95% CI 0.25–0.92)
[28

]. In summary, although CSF drainage is indi-
cated in most extensive open TAAI, its role in endo-
vascular TAAI is evolving, given the significantly
lower risk of spinal cord ischemia. Current guide-
lines recommend selective preoperative CSF drain-
age in patients at high risk for spinal cord
compromise after TEVAR, but this will depend on
the institutional protocol [22

,23]. CSF drainage is
the mainstay of rescue therapy for spinal cord ische-
mia after TAAI, especially if there is incomplete
recovery after several hours of permissive hyper-
tension [22

,23].
MANAGEMENT OF CEREBROSPINAL
FLUID DRAINAGE
Regardless of the specific protocol, the widely
accepted goal is to maintain CSF pressure less than
10–15 mmHg [2,5,29

,30

,31]. Although this CSF
pressure goal is widely accepted, it should also be
titrated to clinical effect and the overall trend in
spinal cord perfusion pressure. For example, if the
awake patient has normal lower extremity muscle
power, then CSF pressure management becomes less
important because at this timepoint the spinal cord
is intact.
Once a CSF drainage catheter has been placed,
the CSF pressure can be maintained at a defined goal
by monitoring the CSF pressure (either continu-
ously or intermittently) and intentionally draining
CSF until either the desired pressure is achieved or a
specific volume has been drained. This procedure is
of particular importance in open TAAI, as appli-
cation of aortic cross clamp (AXC) may induce a
sharp rise in CSF pressure. It occurs in spite of
effective distal perfusion via left-sided bypass and
effective cardiac preload reduction. A possible expla-
nation for the increase in CSF pressure is that AXC
induces a sympathetically mediated vasoconstric-
tion in the systemic and spinal vasculature. This
increased tone in the thin-walled spinal veins may
decrease the critical closing pressure needed to
provoke collapse of the radiculospinal veins as they
pass through the dura, with consequent venous
engorgement and increase in CSF pressure [32].
Possible explanations for the increase in CSF pres-
sure after stent graft deployment might be attrib-
uted to the same cause of sympathetic spinal

stimulation or to the local acidosis-induced veno-
constriction, which occurs in the presence of
inadequate spinal cord perfusion.
(1) If the CSF pressure remains above goal following
drainage, a decision needs to be made if more
will be drained or other maneuvers performed to
optimize spinal cord perfusion pressure.
Though the amount that can ‘safely’ be drained
at a given time has not conclusively been deter-
mined, many experienced centers are limiting
draining to a specified volume of CSF each hour,
but limit hourly maximum drainage to less than
25 ml to avoid complications such as intracra-
nial hematoma from torn subdural bridging
veins [29

,30

,33,34].
(2) Setting the drainage unit at a specific height on a
bedside pole and allowing the CSF to drain freely
as needed. For example, if one levels the drainage
unit to 13 cm above the phlebostatic axis, CSF
will continue to drain as long as CSF pressure
exceeds 10 mmHg (1.3 cm H2O ¼ 1 mmHg). The
advantage of this common method is the auto-
matic maintenance of the desired CSF pressure,
but profound vigilance is required where this
protocol is in use because a serious disadvantage
is the potential for excessive drainage (e.g., if the
drainage unit falls to the floor), which may pre-
dispose to serious complications [30

,34].
Prior to discontinuing and pulling out the CSF
drainage, capping off the drain for 24 h prior to the
removal of the catheter may allow the CSF pressure
to normalize and ascertain whether the patient is
free from spinal cord ischemia as spinal cord
perfusion pressure subsequently decreases [27].
Although this approach is consistent with our
understanding of the SCAN, there are sparse data
to support this practice.
COMPLICATIONS OF CEREBROSPINAL
FLUID DRAINAGE
The complications of CSF catheter insertion and
subsequent drainage include catheter fracture,
infection, CSF leak, abducens nerve palsy, neuraxial
hematoma, and intracranial hematoma [30

,34].
One of the feared complications of CSF drainage
is bleeding, with subsequent potential epidural or
subdural hematoma. Clearly, a frankly ‘bloody tap’
during attempted CSF drain placement will necessi-
tate postponement of the aortic repair, but subdural
bleeding can also occur as a result of CSF drainage
itself because of the tearing of subdural bridging
veins. Excessive CSF drainage was associated with
intracerebral hematomas and with significant
morbidity and mortality [33]. A recent large analysis
from a high-volume center (n ¼ 504, 2005–2009)
demonstrated a 2.8% incidence of intracranial hem-
atoma after CSF drainage for open TAAI: 72% of
these cases were subdural hematomas [30

].
Furthermore, the incidence of postdural puncture
headache was 9.7%, of whom 34.6% required epi-
dural blood patch for clinical resolution [30

]. In
multivariate analysis, connective tissue disorder was
an independent predictor for postdural puncture
headache (OR 3.08; 95% CI 1.33–7.13). The inves-
tigators concluded that the risk of intracranial hem-
atoma was modest, and that epidural blood patch
should be considered early in the management of
postdural puncture headache [30

].
In a smaller, recent, Swedish experience (n ¼ 84,
2009–2012), CSF drainage in endovascular TAAI was
associated with a 3.6% incidence of serious bleeding
complications (one epidural and two subdural hem-
atomas, two of which required neurosurgical inter-
vention) [35]. In summary, CSF drainage has serious
but uncommon complications [33–36]. The clinical
indication for CSF drainage in TAAI must balance
the surgical risks of spinal cord ischemia with the
risks of CSF drainage. In endovascular TAAI, the role
of this neuroprotective intervention will likely be on
a selective basis, given the significantly lower risk of
spinal cord ischemia in this setting.
Pharmacologic neuroprotection
The search for the ideal neuroprotective agent in the
setting of spinal cord ischemia after TAAI has been
vigorous and sustained [2,5]. As the onset of spinal
ischemia in TAAI is typically known, the neuropro-
tective agent could be administered intravenously
or intrathecally either prophylactically or during
ischemia and reperfusion of the spinal cord. Encour-
aging results from the laboratory experiments have
demonstrated promising roles for an array of agents
such as allopurinol, activated protein C, adenosine,
barbiturates, carbamazepine, lidocaine, magnes-
ium, mannitol, naloxone, papaverine, prostaglan-
dins, steroids, and volatile anesthetics [5]. Despite
all these candidate agents, an ideal agent for clinical
administration has yet to be found.
A recent clinical trial from a high-volume center
(n ¼ 330; 250 exposed to papaverine, 2002–2010)
evaluated the neuroprotective effect of intrathecal
papverine as part of a multimodal protocol for spinal
cord protection during open TAAI [37

]. The ration-
ale for this intervention is that papaverine, as a
vasodilator, will increase spinal cord perfusion,
particularly in the narrowed lower thoracic area,
when given in the intrathecal space. Exposure to
papaverine as part of a multimodal spinal protection
protocol in this trial significantly reduced the risk of

permanent paraplegia (3.6 vs. 7.5%; P ¼ 0.01) and
paraparesis (1.6 vs. 6.3%; P ¼ 0.01) [37

]. The inves-
tigators concluded that papaverine likely provides
additional neuroprotection in this setting.
The multiplicity of neuroprotective agents
points to an inadequate understanding of ischemia
and reperfusion in the spinal cord after TAAI from a
pharmacologic perspective. Recently, investigators
have focused attention on the resident macrophages
in the spinal cord (the microglia) that are thought to
play a central role in the development of neural
death during spinal cord ischemia [38,39,40

]. A
laboratory study in rats demonstrated that exposure
to the macrolide antibiotic, minocycline, during
spinal cord ischemia from thoracic aortic occlusion
not only inhibits spinal microglia, but also signifi-
cantly protects against the clinical development of
paraplegia [40

]. This promising study has identified
a novel cellular target for further study and possibly
a clinical trial in the future.
In summary, although a multiplicity of agents
have shown promise in the laboratory, there are to
date no robust randomized clinical trials supporting
the efficacy of a single agent for spinal cord neuro-
protection in TAAI. It appears that steroids are the
most frequently administered agents for neuropro-
tection during open TAAI, but this practice is based
on limited evidence [5]. Given the low risk of spinal
cord ischemia and expanding clinical applications
of endovascular TAAI, it is likely that this practice
will gradually disappear unless future clinical trials
strongly support an agent.
Intensive neuromonitoring of the spinal cord
In the awake patient after TAAI, serial neurologic
assessmentwilldetectthedevelopmentofspinalcord
ischemia. This diagnosis should urgently trigger a
protocol for spinal cord rescue, including permissive
systemic hypertension with or without CSF drainage
[1,2,3

].Intheanesthetizedandhenceuncooperative
patient during TAAI, intraoperative detection of spi-
nal cord ischemia typically relies on neuromonitor-
ing with somatosensory-evoked potentials and
motor-evoked potentials [4,5,6

,41,42].
The intraoperative detection of spinal cord
ischemia during TAAI is critical because it signifi-
cantly correlates with the development of paraple-
gia and poor perioperative outcome [41,42]. The
intraoperative diagnosis by transcranial motor-
evoked potentials (tcMEPs) gives the team the
opportunity to intervene to enhance spinal cord
perfusion and save the spinal cord. It is essential to
tailor the anesthetic plan so as to maximize the
preservation of neural signals both for somatosen-
sory-evoked potentials and tcMEPs [4,5,6

,41,42]. A
critical disadvantage of tcMEPs is the high sensitivity
to volatile anesthetics and muscle relaxants. Thus,
when tcMEP monitoring is planned, intravenous
anesthesia should be used with minimal volatile
anesthetics or muscle relaxants. This will minimize
the interference with the signal profiles from medi-
cations and maximize the detection of spinal cord
ischemia. Anesthetic interventions to maximize
spinal cord oxygen delivery in this setting include
systemic hypertension, augmented CSF drainage,
and red blood cell transfusion for correction of ane-
mia [22

,23]. Surgical interventions to maximize the
spinal protection will depend on the stage and type of
TAAI but might include augmentation of distal aortic
perfusion, control of bleeding, reimplantation of
intercostal arteries, and staging of the TAAI to allow
recovery of the SCAN [5,43–45]. In summary, com-
prehensive evaluation of spinal cord function
remains essential during the entire perioperative
period in patients undergoing TAAI. In high-risk
patients for spinal cord injury, spinal cord monitor-
ingwithevokedpotentialsisindicated.Thedetection
of spinal cord ischemia should urgently trigger inter-
ventions forspinal cord rescue, based on institutional
protocol, patient factors, and team discussion. The
importance of clinical experience, clear communi-
cation, and seamless teamwork all contribute signifi-
cantly to prompt and successful reversal of spinal
cord ischemia in this challenging setting.
CONCLUSION
The recent progress in TAAIs has resulted in better
freedom from spinal cord ischemia for our patients,
although this devastating complication still occurs.
The promising areas of investigation in the near
future will likely involve refinements in endovascu-
lar aortic techniques and a multimodality approach,
both for enhanced spinal cord protection in these
challenging aortic procedures.
Acknowledgements
Financial support: Institutional.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
of special interest
of outstanding interest
1. Desart K, Scali ST, Feezer RJ, et al. Fate of patients with spinal cord ischemia
complicating thoracic endovascular aortic repair. J Vasc Surg 2013; 58:635–
642.

2. Vaughn SB, Lemaire SA, Collard CD. Case scenario: anesthetic considera-
tions for thoracoabdominal aortic aneurysm repair. Anesthesiology 2011;
115:1093–1102.
3.

Becker DA, McGarvey ML, Rojvirat C, et al. Predictors of outcome in patients
with spinal cord ischemia after open aortic repair. Neurocrit Care 2013;
18:70–74.
This interesting study highlights in a contemporary series from an experienced
center the negative outcome effects of spinal cord ischemia after extensive open
aortic repairs.
4. Drenger B, Parker S, McPherson RW, et al. Spinal stimulation evoked
potentials during thoracoabdominal aortic aneurysm surgery. Anesthesiology
1992; 76:689–695.
5. Augoustides JGT. Spinal cord protection strategies. In: Subramaniam K, Park
KW, Subramaniam B, editors. Anesthesia and perioperative care for aortic
surgery. New York, USA: Springer; 2011. pp. 239–256; Chapter 11..
6.

Sloan T, Edmonds HL, Koht A. Intraoperative electrophysiologic monitoring in
aortic surgery. J Cardiothorac Vasc Anesth 2013; 27:1364–1373.
This review article discusses in detail the details of somatosensory and motor
evoked potentials for spinal cord monitoring in thoracoabdominal aortic proce-
dures.
7. Andritsos M, Desai ND, Grewal A, et al. Innovations in aortic disease
management: the descending aorta. J Cardiothorac Vasc Anesth 2010;
24:523–529.
8. Coady MA, Ikonomidis JS, Cheung AT, et al. Surgical management of
descending thoracic aortic disease: open and endovascular approaches: a
scientific statement from the American Heart Association. Circulation 2010;
121:2780–2804.
9. Etz CD, Kari FA, Mueller CS, et al. The collateral network concept: a
reassessment of the anatomy of spinal cord perfusion. J Thorac Cardiovasc
Surg 2011; 141:1020–1028.
10. Bischoff MS, Di Luozzo G, Griep EB, et al. Spinal cord preservation in
thoracoabdominal aneurysm repair. Perspect Vasc Surg Endovasc Ther
2011; 23:214–222.
11.

Griepp RB, Di Luozzo G. Hypothermia for aortic surgery. J Thorac Cardiovasc
Surg 2013; 145:S56–S58.
This article discusses in detail the evidence supporting hypothermia for spinal cord
protection in thoracoabdominal aortic procedures.
12.

Kouchoukos NT. Thoracoabdominal aortic aneurysm repair using hypother-
mic cardiopulmonary bypass and circulatory arrest. Ann Cardiothorac Surg
2012; 1:409–411.
This interesting study highlights in a contemporary series from an experienced
center the excellent outcomes with deep hypothermic circulatory arrest after
extensive open aortic repairs.
13.

Yan TD, Bannon PG, Bavaria J, et al. Consensus on hypothermia in aortic arch
surgery. Ann Cardiothoracic Surg 2013; 2:163–168.
This expert consensus study presents a rationale for the classification of hypother-
mia in aortic surgery.
14. Kouchoukos NT, Kulik A, Castner CF. Outcomes after thoracoabdominal
aortic aneurysm repair using hypothermic circulatory arrest. J Thorac Cardio-
vasc Surg 2013; 145:S139–S141.
15. Corvera JS, Fehrenbacher JW. Open repair of chronic aortic dissections
using deep hypothermia and circulatory arrest. Ann Thorac Surg 2012;
94:78–81.
16. Fehrenbacher JW, Siderys H, Terry C, et al. Early and late results of
descending thoracic and thoracoabdominal aortic aneurysm open repair with
deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg 2010;
140:S154–S160.
17. Leshnower BG, Szeto WY, Pochettino A, et al. Thoracic endografting reduces
morbidity and remodels the thoracic aorta in DeBakey III aneurysms. Ann
Thoracic Surg 2013; 96:914–921.
18. Canaud L, Karthikesalingam A, Jackson D, et al. Clinical outcomes of single
versus staged hybrid repair for thoracoabdominal aneurysm. J Vasc Surg
2013; 58:1192–1200.
19.

Zipfel B, Buz S, Redlin M, et al. Spinal cord ischemia after thoracic stent-
grafting: causes apart from intercostals artery coverage. Ann Thorac Surg
2013; 96:31–38.
This interesting article discusses how thoracoabdominal endovascular aortic
repair evolved at a high-volume institution over time, based on an understanding
and clinical application of the spinal collateral arterial network concept.
20. Etz CD, Kari FA, Mueller CS, et al. The collateral network concept: remodeling
of the arterial collateral network after experimental segmental arterial sacrifice.
J Thorac Cardiovasc Surg 2011; 141:1029–1036.
21. Ullery BW, Wang GJ, Low D, et al. Neurological complications of thoracic
endovascular aortic repair. Semin Cardiothorac Vasc Anesth 2011; 15:123–
140.
22.

Grabenwoger M, Alfonso F, Bachet J, et al. Thoracic endovascular repair
(TEVAR) for the treatment of aortic diseases: a position statement from the
European Association for Cardio-Thoracic Surgery (EACTS) and the Eur-
opean Society of Cardiology (ESC), in collaboration with the European
Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart
J 2012; 33:1558–1563.
This comprehensive guideline presents a guideline-based endovascular approach
to thoracoabdominal aortic diseases with recommendations based on clear levels
of evidence and clinical benefit.
23. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/
ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and manage-
ment of patients with thoracic aortic disease. A report of the American College
of Cardiology/American Heart Association Task Force on Practice Guide-
lines, American Association for Thoracic Surgery, American College of
Radiology, American Stroke Association, Society of Cardiovascular Anesthe-
siologists, Society of Cardiovascular Angiography and Interventions, Society
of Interventional Radiology, Society of Thoracic Surgeons and Society of
Vascular Medicine. J Am Coll Cardiol 2010; 55:e27–e129.
24. Bobadilla JL, Wynn M, Tefera G, et al. Low incidence of paraplegia after
thoracic endovascular aneurysm repair with proactive spinal cord protective
protocols. J Vasc Surg 2013; 57:1537–1542.
25. Keith CJ, Passman MA, Carignan MJ, et al. Protocol implementation of
selective postoperative lumbar spinal drainage after thoracic aortic endograft.
J Vasc Surg 2012; 55:1–9.
26. Hanna JM, Andersen ND, Hamza A, et al. Results with selective preoperative
lumbar drain placement for thoracic endovascular aortic repair. Ann Thorac
Surg 2013; 95:1968–1975.
27. Ullery BW, Cheung AT, Fairman RF, et al. Risk factors, outcomes, and clinical
manifestations of spinal cord ischemia following thoracic endovascular aortic
repair. J Vasc Surg 2011; 54:677–684.
28.

Wong CS, Healy D, Canning C, et al. A systematic review of spinal cord injury
and cerebrospinal fluid drainage after thoracic aortic endografting. J Vasc
Surg 2012; 56:1438–1447.
This comprehensive meta-analysis demonstrates the low incidence of spinal cord
ischemia in endovascular aortic techniques, despite the low quality of evidence.
29.

Khan SN, Stansby G. Cerebrospinal fluid drainage for thoracic and thora-
coabdominal aortic aneurysm surgery. Cochrane Database Syst Rev 2012;
10:CD003635.
This comprehensive meta-analysis demonstrates the benefits of cerebrospinal fluid
drainage in open thoracoabdominal interventions.
30.

Youngblood SC, Tolpin DA, LeMaire SA, et al. Complications of cerebrospinal
fluid drainage after thoracic aortic surgery: a review of 504 patients over
5 years. J Thorac Cardiovasc Surg 2013; 146:166–171.
This is the best recent review of lumbar drain complications after thoracic aortic
surgery from an experienced and high-volume center.
31. Bilal H, O’Neill B, Mahmood S, et al. Is cerebrospinal fluid drainage of benefit
to neuroprotection in patients undergoing surgery on the descending thoracic
aorta or thoracoabdominal aorta. Interact Cardiovasc Thorac Surg 2012;
15:702–708.
32. Drenger B, Parker SD, Frank SM, Beattie C. Changes in cerebrospinal fluid
pressure and lactate concentrations during thoracoabdominal aortic aneur-
ysm surgery. Anesthesiology 1997; 86:41–47.
33. Dardik A, Perler BA, Roseborough GS, et al. Subdural hematoma after
thoracoabdominal aortic aneurysm repair: An underreported complication
of spinal fluid drainage? J Vasc Surg 2002; 36:47–50.
34. Fedorow CA, Moon MC, Mutch AC, et al. Lumbar cerebrospinal fluid drainage
for thoracoabdominal aortic surgery: rationale and practical considerations for
management. Anesth Analg 2010; 111:46–58.
35. MehmedagicI,ReschT,AcostaS.Complicationstocerebrospinalfluiddrainage
andpredictorsofspinalcordischemiainpatientswithaorticdiseaseundergoing
advanced endovascular therapy. Vasc Endovasc Surg 2013; 47:415–422.
36. Leyvi G, Ramachandran S, Wasnick JD, et al. Risks and benefits of cere-
brospinal fluid drainage during thoracoabdominal aortic aneurysm surgery.
J Cardiothor Vasc Anesth 2005; 19:392–399.
37.

Lima B, Nowicki ER, Blackstone EH, et al. Spinal cord protection strategies
during descending and thoracoabdominal aortic aneurysm repair in the
modern era: the role of intrathecal papaverine. J Thorac Cardiovasc Surg
2012; 143:945–952.
This clinical trial presents evidence supporting papaverine as part of a multimodal
protocol for spinal cord protection in thoracoabdominal aortic procedures.
38. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of
inflammatory cells. J Leukoc Biol 2010; 87:779–789.
39. Drenger B, Fellig J, Barzilay Y. Minocycline-induced spinal cord protection
from aortic occlusion-related ischemia in the rabbit model. Anesth Analg
2010; 110:S-39.
40.

Smith PD, Bell MT, Puskas F, et al. Preservation of motor function after spinal
cord ischemia and reperfusion injury through microglial inhibition. Ann Thorac
Surg 2013; 95:1647–1653.
This interesting clinical trial presents the laboratory evidence supporting minocy-
cline as part of multimodal protocol for spinal cord protection in thoracoabdominal
aortic procedures.
41. McGarvey ML. Effective tool or necessary evil: intraoperative monitoring during
thoracic aneurysm repairs. J Clin Neurophysiol 2012; 29:154–156.
42. BeckerDA,McGarveyML,RojviratC,etal.Predictorsofoutcomeinpatientswith
spinal cord ischemia after open aortic repair. Neurocrit Care 2013; 18:70–74.
43. Hsu CC, Kwan GN, van Driel ML, et al. Distal aortic perfusion during
thoracoabdominal aneurysm repair for prevention of paraplegia. Cochrane
Database Syst Rev 2012; 3:CD008197.
44. Ullery BW, Wang GJ, Woo EY. No increased risk of spinal cord ischemia in
delayed AAA repair following thoracic aortic surgery. Vasc Endovasc Surg
2013; 47:85–91.
45. Hughes GC, Andersen ND, Hanna JM, et al. Thoracoabdominal aortic aneur-
ysm: hybrid repair outcomes. Ann Cardiothorac Surg 2012; 1:311–319.

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