Keywords
spinal cord ischemia - neurological deficits - open repair - endovascular repair
Introduction
Spinal cord ischemia (SCI) is one of the major and most dreadful complications that
may follow thoracic and thoracoabdominal (TAA) aortic repair, both open and endovascular,
and it may result in devastating physical disabilities, but also in a much-reduced
survival at follow-up.
SCI may cause several degrees of neurological deficits from temporary or permanent
paraparesis to complete flaccid paraplegia. However, mobility impairment is only a
part of the clinical syndrome. The lack of mobility and sensitivity in the lower half
of the body is responsible for bedsores that can evolve into severe infections. Fecal
and urinary incontinence may also result in recurrent infections and are psychologically
poorly tolerated. Deep venous thrombosis is another possible adjunctive complication
in patients with complete or partial lack of mobility. Moreover, postoperative SCI
may affect elderly patients, with preexisting respiratory, cardiac, and renal comorbidities.
This explains the very poor survival rate of patients with the more severe forms.
The pathogenesis of spinal cord (SC) damage during TAA procedures, while multifactorial,
is mainly due to an ischemic insult. Concerning the onset of symptoms, neurological
damage may be immediate (during or at the end of the procedure) or delayed (after
a period of normal neurological function). Immediate SCI mainly results from a temporary
or permanent reduction of SC blood supply. A delayed deficit may be due to an SC perfusion
impairment but also can result from an ischemia/reperfusion mechanism, with SC swelling
edema within the bony spinal canal and a consequent increase in cerebrospinal fluid
(CSF) pressure. Moreover, some authors speculate that the intraoperative ischemic
insult induces a programmed neuronal cell death.[1] Others, also consider the role of late thrombosis of intercostal arteries as another
possible pathogenetic factor.
During recent decades, improvements have been made in both open and endovascular TAA
repairs. However, SCI is still an open issue in this field, and its pathophysiology
is still poorly understood. A multimodal approach, based on a deep knowledge of the
SC anatomy, along with different protective adjuncts, may be considered to prevent
SCI for both open and endovascular TAA repairs.
Spinal Cord Anatomy
SC blood supply is characterized by extreme interindividual variability, but it generally
presents two vasculature pathways, an extrinsic and an intrinsic one.
The extrinsic system includes:
The intrinsic system includes two different systems:
-
a central system (centrifugal) fed by the sulcal arteries.
-
a peripheral system (centripetal) with perforating branches originating from the pial
network.
The intercostal arteries divide three times to reach the anterior spinal artery (ASA)
which supplies blood to the spinal gray matter:
-
The first branch of the intercostal artery is the nervomedullary artery.
-
The latter divides into an anterior and posterior radicular artery.
-
The anterior radicular artery divides into a descending and an ascending branch.
An anastomotic channel between ascending and descending branches of neighboring anterior
radicular arteries creates the ASA during the embryonic and fetal stages. However,
in the adult, only at few levels, the anterior and posterior radicular arteries cross
the dura to reach the surface of the medulla. In the thoracolumbar region, one (occasionally
two or three) anterior radicular artery is dominant in caliber and is therefore called
the great radicular artery or arteria radicularis magna (ARM), or the artery of Adamkiewicz
([Fig. 1]). A more detailed description of SC vascularization anatomy has been previously
published.[2]
Fig. 1 With preoperative computed tomography angiography, using postprocessing tools, the
whole path of the arterial feeder to the spinal cord can be visualized, from the aorta
to the anterior spinal artery (A: intercostal artery; B: anterior radicular artery;
C: arteria radicularis magna or artery of Adamkiewicz; D: anterior spinal artery).
Many other vessels provide an inflow to these systems, such as the subclavian artery
and the hypogastric arteries. Griepp and Griepp[3] introduced the “collateral network concept,” detailing the redundancies in the blood
supply to the SC and its significant anatomic variability. While this “collateral
network” may guarantee adequate vascularization in many instances, this is not always
the case in an acute setting. Aortic interventions could affect at different levels
the inflow arteries of the network, and this may explain the physiopathology of SC
ischemia in many circumstances. Deep knowledge of the SC vasculature anatomy in the
individual patient is therefore essential for accurate risk stratification and a tailored
approach focused on SCI prevention.
Mechanism of Spinal Cord Injury and Prevention Strategies during Thoracoabdominal
Open Repair
Mechanism of Spinal Cord Injury and Prevention Strategies during Thoracoabdominal
Open Repair
A temporary reduced perfusion of the SC feeders is substantially inevitable during
aortic cross-clamping, and the sacrifice of some intercostal/lumbar arteries is often
needed surgically. Several prevention protocols and treatment strategies have been
proposed over recent years to maintain an adequate SC perfusion during open repair.
Minimize Spinal Cord Ischemic Time
During TAA open surgery, the aortic cross-clamp time is one of the most significant
predictors of postoperative SCI, with a reported incidence up to 27% in patients with
an aortic cross-clamp time >60 minutes. Thus, an expeditious aortic surgery has generally
been advocated since the early years of this surgery. In addition, sequential aortic
clamping and techniques for distal aortic perfusion were introduced to maintain the
blood supply of the SC feeding vessels during the aortic clamping time. Left heart
bypass (LHBP) associated with sequential clamping, compared with the simple “clamp
and sew” technique, has been demonstrated to be protective against SCI.[4] LHBP plays a crucial role, especially in case of extensive repair and when unexpected
complications occur, and its effectiveness in reducing the SCI rate has been recently
confirmed by experienced aortic centers ([Fig. 2]).[5]
Fig. 2 Schematic view of left heart bypass. (A) A 20-Fr cannula is inserted in one of the left pulmonary veins for the arterial
blood drainage. (B) Through a centrifugal pump, the oxygenated blood is routed into the left femoral
artery for synchronous proximal (visceral and intercostal vessels) and (C) distal perfusion during sequential clamping, using a nonocclusive femoral cannula.
(D) A “Y” connector provides two occlusion/perfusion catheters for selective visceral
perfusion with blood.
Preserve Spinal Cord Blood Supply
During TAA open repair, it is possible to reattach some intercostal arteries, but
the effective role of reimplantation in terms of SCI prevention remains controversial.
Some authors advocate an expeditious aortic repair with no intercostal artery reattachment,
being confident in the SC collateral network.[6] However, the protective role of critical intercostal artery (T8–L2) reattachment
to reduce the risk of postoperative SCI has been extensively demonstrated over the
years.[7] With this approach, during the procedure, patent intercostal critical arteries are
temporarily occluded to prevent back-bleeding and then selectively reattached to the
graft by means of an aortic patch or graft interposition ([Fig. 3]). This procedure, however, is time-consuming, and large aortic patches may be prone
to future dilatation. Thus, it would probably be better to avoid unnecessary reattachments,
especially in patients with connective tissue disorders and, in general, in patients
with bad quality aortic tissue.
Fig. 3 Critical intercostal arteries reattachment during thoracoabdominal aortic aneurysm
open surgical repair with three different techniques. (A) An aortic island including the origin of several intercostal arteries is reattached
to a fenestration created on the aortic graft. (B) Intercostal arteries are reattached selectively to the graft via 6/8-mm interposition
grafts. (C) Another possible way to reattach critical intercostal arteries is represented by
the “loop graft”; a 14/16-mm is anastomosed proximally and distally to the aortic
graft. A fenestration is created in this loop graft to reattach the origin of multiple
intercostal arteries (dotted circle). TAAA, thoracoabdominal aortic aneurysm.
Recent advances in preoperative imaging may play a role in planning selective reimplantation
of critical intercostal feeders. Modifications of intraprocedural neurophysiologic
monitoring tools are also extremely helpful to identify critical SC feeders.
Increased Spinal Cord Tolerance to Ischemia
A neuronal injury may develop rapidly after ischemia under normothermic conditions.
Mild systemic hypothermia (32–34°C) may play a protective role on SC, decreasing SC
metabolic demands, with consequent attenuation of the inflammatory cascade response.
Some authors perform extensive TAA repair under deep hypothermia (15–18°C) and circulatory
arrest, gaining the maximum advantage from the protective effects of hypothermia.[1] However, this technique may be limited by coagulopathy and pulmonary and cerebral
complications. A selective SC hypothermic protection, by regional cooling with an
infusion of cold 4°C saline solution in the epidural space during ischemic periods,
has also been proposed, with interesting results.[8]
Optimization of Spinal Cord Perfusion
Optimizing SC perfusion by raising arterial systemic blood pressure and reducing CSF
pressure are also key points for the prevention and treatment of SCI.
Arterial Systemic Blood Pressure
Hemodynamic stability during the procedure and the postoperative period is very important,
and, in general, the mean arterial pressure (MAP) should be maintained over 70 mm
Hg. The surgeon plays a major role to ensure the control of hemorrhage, and anesthesiologist
and perfusionist need to be prepared to manage large blood losses and to ensure continuous
organ perfusion.
Equally, an intensive care unit needs to be familiar with all aspects of TAA postoperative
care to maintain adequate hemodynamic stability in the postoperative period. Arterial
pressure should be monitored carefully after open TAA repair to avoid unintentional
postoperative hypotension that may precipitate SCI.
Extensive TAA repair is a demanding procedure for the whole cardiovascular system,
and many of these patients come to surgery with preoperative coronary lesions. To
avoid the hemodynamic instability secondary to perioperative cardiac events, an accurate
preoperative cardiac evaluation is advocated in all patients undergoing elective TAA
repair.[9]
Cerebrospinal Fluid Pressure
CSF pressure rises immediately after SC perfusion impairment, and this mechanism,
coupled with decreased SC perfusion pressure, may be one of the major causes of SCI.
The preoperative placement of SC drainage allows intra- and postoperative CSF continuous
pressure monitoring and drainage and represents a widely practiced technique during
TAA surgery. CSF drainage to maintain CSF pressure <10 cm H20 has been demonstrated to be effective in paraplegia reduction in cases of extensive
TAA repair and also in cases of delayed onset of paraplegia.[10] Although the safety of CSF drainage appears to be acceptable, serious and even fatal
complications associated with its placement have been reported.[11] Nowadays, CSF drainage may be performed with an automated device with several advantages
that have been previously reported ([Fig. 4]).[12]
Fig. 4 (A) Once the dura has been punctured with the introducer needle, (B) a drainage catheter is inserted 8 to 10 cm along the intradural space. The catheter
is then connected to a pressure transducer, and the fluid is drained to keep the pressure
below 10 cm H2O. (C) Automated systems, such as Liquoguard, are available for this purpose.
Early Detection of Spinal Cord Ischemia
Early detection of SCI is critical to allow prompt intervention before ischemia evolves
to infarction and consequent permanent neurological deficits. In patients under general
anesthesia, neurological monitoring of SC function can be obtained with somatosensory-evoked
potentials (SSEP), and motor evoked potentials (MEP), or both. Technical details of
these techniques have previously been extensively reported.[13] The immediate detection of intraoperative SCI, obtained with the usage of MEP and
SSEP monitoring, allows one to trigger prompt anesthesiologic and surgical maneuvers
for maximizing SC perfusion and potentially rapidly reversing SC injury.
In patients with MEP and SSEP modifications, increasing distal aortic pressure with
LHBP, and CSF drainage are possible ways to restore an adequate SC perfusion. Moreover,
aortic replacement performed with sequential cross-clamping maximizes the effect of
distal perfusion and may be helpful to identify the critical segments of the aorta
that supply to the SC, with possible intercostal artery reattachment. Notably, SC
neurological monitoring can be affected by anesthetic agents, which may induce a depressed
neural response; thus, sometimes false positive results may be obtained.
Other noninvasive methods to obtain valuable monitoring of SC perfusion have been
proposed. In particular, with near-infrared spectroscopy, an effective monitoring
of paraspinous muscle oxygenation can be obtained, as a surrogate for SC perfusion.[14] An alteration in CSF biochemical markers consequent to SCI can be identified to
detect ischemia promptly. However, the usage of these markers in clinical practice
is still limited.
Mechanism of Spinal Cord Injury and Prevention Strategies during Endovascular Repair
Mechanism of Spinal Cord Injury and Prevention Strategies during Endovascular Repair
When feasible, thoracic endovascular aortic repair (TEVAR) reduces the morbidity of
surgical access and avoids the need for aortic cross-clamping. In the last two decades,
technological improvements have offered the opportunity to treat even extensive TAA
with endovascular procedures, utilizing fenestrated and branched endovascular devices
(F/B-EVAR). These procedures incur also an intrinsic risk of SCI, with different pathophysiological
patterns from open repair:
-
Aortic cross-clamping is avoided
-
The number of intercostal arteries sacrificed is larger, and they cannot be reattached
to the graft. If compared with open repair, longer aortic segments are covered by
the stent graft (SG) to anchor in healthy aortic necks.
-
Manipulation of endovascular devices in the diseased aorta may induce embolic complications
contributing to the SC.
Endovascular procedures, without the background noise of aortic cross-clamping and
intercostal artery reattachment, offer the opportunity to evaluate the physiopathology
of SC ischemia and to understand the importance of the different SC feeders without
possible confounding factors. An analysis of data collected in the European Registry
of Endovascular Aortic Repair Complications pointed out the importance of the various
SC feeders. Czerny et al[15] demonstrated that extensive coverage of intercostal arteries by a TEVAR alone is
not associated with SC ischemia, while simultaneous closure of at least two vascular
territories (left subclavian artery (LSA), intercostal, lumbar, and hypogastric arteries)
supplying the SC is relevant, especially if associated with prolonged intraoperative
hypotension. Thus, different prevention protocols have been proposed to preserve SC
feeders and maintain an adequate SC perfusion, during the endovascular repair.
Left Subclavian Artery Revascularization
In the recent past, to obtain an adequate proximal aortic neck during TEVAR, an intentional
LSA overstenting without LSA revascularization has frequently been performed. However,
multiple studies demonstrated that increased risks of stroke and SCI are associated
with LSA occlusion without previous revascularization.[16] Nowadays, in case of elective extensive aortic coverage, preventive LSA revascularization
is recommended by society guidelines (grade IIa, level C).[9]
Intercostal and Lumbar Arteries Sacrifice
An intrinsic drawback of TEVAR is the sacrifice of the intercostal arteries that arise
not only from the aneurysm but also from the healthy aorta at the level of proximal
and distal landing zones. The coverage of an aortic segment > 20 cm with TEVAR was
reported to be associated with SCI, and recently published experience of extensive
TAA repair with F/B-EVAR has also demonstrated a significant association between SCI
and the extent of aortic coverage.[17]
Different considerations should be made for TEVAR alone and F/B-EVAR procedures. While
endovascular repair with F/B-EVAR needs a distal landing zone in the infrarenal aorta
in the majority of cases, in cases of pure thoracic endovascular repair, the distal
landing zone is generally above the origin of the celiac trunk. During TEVAR, the
length of the uncovered distal thoracic aorta and the distance between the SG and
the celiac trunk are associated with the risk of SCI, with a risk reduction of 40%
for each 2 cm of the distal thoracic aorta above the celiac trunk left uncovered.[18]
Thus, accurate preoperative planning and the identification of a distal landing zone
able to preserve critical SC feeders, as well as avoiding unnecessary aortic coverage,
are key points in SCI prevention during TEVAR.
An anecdotal experimental study with side small caliber branches for intercostal artery
preservations during TEVAR has been reported but mid- and long-term results of these
pioneering procedures are still unknown.
During extensive TAA endovascular repair with F/B-EVAR, off-the-shelf devices often
require more extensive proximal aortic coverage due to intrinsic manufacturing characteristics.[19] While it is possible to avoid the unnecessary sacrifice of the native healthy aorta
with custom-made devices, the possibility to preserve ARM feeders during these procedures
is limited, and different approaches have been developed.
One interesting concept that has emerged in the last few years is that the SC vasculature
may have the potential to be “preconditioned” to better tolerate the occlusion of
the segmental suppliers, such as the intercostal or lumbar arteries. This preconditioning
may be obtained by staging the aortic procedures so that the occlusion of the segmental
feeders is done in two or three steps. This staged approach has been demonstrated
to lower the risk of perioperative SCI significantly.[20]
Etz et al[21] proposed selective segmental intercostal artery endovascular coil embolization for
preconditioning the collateral network toward minimizing ischemic SC injury, with
promising results ([Fig. 5]). To evaluate the safety and efficacy of this procedure, for both open surgical
and endovascular TAA procedures, a prospective, multicenter, international, randomized
clinical trial (PAPAartis) has been designed. The study will require several more
years to complete enrollment and analyze the results.
Fig. 5 (A) Preoperative computed tomography angiography (AngioCT) is used for the identification
of critical intercostal arteries. According to the preoperative spinal cord (SC) vasculature
imaging, the occlusion of SC feeders may be planned to induce a collateral network
preconditioning. (B) With the aid of intraoperative adjuncts, such as the fusion technique, an easier
identification of the intercostal arteries is possible during the endovascular procedure.
With this imaging tool, the preoperative AngioCT is matched with the intraoperative
angiography, with the possibility to underline the aortic contour and preoperatively
selected vessels, such as the intercostal arteries (*). This approach allows an easier
identification of the intercostal vessels for catheterization. (C) Embolization with coils may be performed to selectively occlude the intercostal
artery.
Role of Hypogastric Arteries
The role of the hypogastric arteries as SC feeders has been progressively clarified
during the last decade. It has been demonstrated that the chance of developing SCI
is significantly higher in patients with an occluded or excluded hypogastric artery.[22] Similarly, a significant correlation between embolic occlusion of the hypogastric
arteries and the development of SCI was documented in patients with the endovascular
abdominal aortic repair. Maurel et al[23] demonstrated that early restoration of arterial flow to the pelvis and lower limbs
significantly reduces the risk of SC ischemia due to the occlusive effect of large
sheaths left in place for extended times during complex endovascular procedures to
treat thoracoabdominal aneurysms. For these reasons, different surgical and endovascular
maneuvers able to restore early antegrade perfusion of hypogastric arteries during
endovascular procedures have been proposed.
Bleeding and Hypotension
Hypotension is an established factor in the genesis of SCI due to a temporary impairment
of SC vascularization. After the coverage of intercostal and lumbar arteries, the
compensation of the collateral network may be insufficient in case of hemodynamic
instability with hypotension, with consequent temporary SC ischemia. Via prompt identification
and reversal of hypotension, possible SC deficits may be completely resolved, while
prolonged impairment in SC perfusion may lead to irreversible neurological deficits.
During the procedure, excessive blood and fluid loss, caused by arterial injuries
or even by surgical procedures like an iliac conduit, may lead to hypotension and
have been implicated as a possible cause of SCI during the endovascular repair.[24] Notably, excessive bleeding from endovascular devices may also complicate very long
procedures (>300 minutes), even with a percutaneous approach; thus, continuous intraoperative
monitoring of the hematocrit is recommended. If a lowering of the systemic pressure
is needed during the SG deployment, to avoid a prolonged hypotensive phase, maneuvers
such as rapid cardiac pacing and balloon inflation in the inferior vena cava are more
rapidly reversible compared with antihypertensive drugs.
During the postoperative course, the use of excessive antihypertensive therapies should
be avoided and hemodynamic stability with a MAP >70 mm Hg should be maintained.
Adjunctive Maneuvers to Detect, Prevent, and Treat Spinal Cord Ischemia
While the protective role of CSF drainage (CSFD) during thoracoabdominal aortic aneurysm
(TAAA) open surgical repair has been widely reported, its effective role during endovascular
procedures still needs to be completely established. Moreover, CFSD involves a nonnegligible
risk of related complications, from minor issues such as headaches to potentially
devastating issues such as spinal hematoma or intracranial hemorrhage. For these reasons,
the prophylactic use of preoperative CSFD before complex endovascular procedures should
be weighed carefully, and many authors suggest its usage only in patients preoperatively
considered at high risk for SCI.[11]
As for open TAAA repair, intraoperative neuromonitoring with MEP and SSEP may play
a role also during complex endovascular procedures for early detection of impairments
in SC supply, application of adjunctive maneuvers, and possible prevention of ischemic
damage. In contrast to open surgical repair, intercostal artery reattachment is not
feasible during endovascular procedures, but other adjunctive maneuvers may increase
direct or indirect perfusion of the SC collateral network. Adjunctive maneuvers in
response to MEP and SSEP deficits may include incremental changes in mean arterial
pressure, as well as an increase in CSFD when a prophylactic spinal drain catheter
has been preoperatively placed. If the above-mentioned maneuvers are not sufficient
to obtain MEP and SSEP normalization, other technical modifications of the procedure
are possible, such as the early restoration of flow to the lower extremity and to
the pelvis, or even the interruption of the endovascular repair to restore direct
perfusion of the aneurysm sac.[25]
Endoelak Resolution
After endovascular procedures, SCI can be immediate or delayed. While immediate neurological
deficits are explained by the occlusion of critical intercostal arteries, delayed
SCI may be consequent to hypotension, anemia, or late loss of collaterals. The thrombosis
within the excluded aneurysm sac may not be immediate, especially in the case of endoleaks.
After endoleak resolution, complete thrombosis of the aneurysmal sac generally occurs,
with possible late occlusion of patent critical intercostal arteries, making the collateral
network insufficient and incurring delayed onset of SCI. Thus, in the case of SCI,
ancillary endovascular maneuvers aimed at voluntarily creating a temporary endoleak
have been described.
Conclusion
Several improvements have been made during recent decades in understanding the mechanisms
of SC injury. Nowadays, it is clear that many different factors contribute to cause
postoperative paraparesis or paraplegia after both open and endovascular management
of TAAA. Side by side with a better knowledge of the different pathophysiological
patterns, a multimodal approach to prevent SCI has been developed. A combination of
many intraoperative and postoperative maneuvers, both surgical and anesthesiological,
may contribute to optimize the SC blood supply and ameliorate its tolerance to ischemia.
With this multimodal approach, better results have been reached compared with the
past, but the problem of this dramatic complication is still not solved after either
open or endovascular TAAA repair. Further focused research is still needed to improve
outcomes.
