A multimodal approach to prevent spinal cord ischemia in patients undergoing thoracoabdominal aortic aneurism repair - from pathophysiology to anesthesiological management

Abstract

Thoraco-abdominal aortic aneurysm (TAAA) open repair is a high-risk surgery further burdened with both mortality and morbidity. Despite numerous experimental endeavors and technical advancements, spinal cord ischemia (SCI) is still the most formidable morbidity to be resolved, irrespective of the open or endovascular surgical approach. It presents a spectrum of severity, ranging from temporary or permanent paraparesis to paraplegia with or without autonomic dysfunction. The timing of SCI occurrence is a crucial factor, with approximately 15% of cases manifesting intraoperatively, 50% within 48 h post-surgery, and the remaining 35% classified as late SCI, occurring more than 48 h after the procedure. The mechanism responsible for SCI is complex and multifactorial; hence, understanding its underlying pathophysiology is essential for its effective management. Over the last decade, strategies to enhance spinal cord perfusion and minimize the risk of SCI during TAAA open repair have been implemented. These include optimization of hemodynamics, hemoglobin levels, cardiac function, and cerebrospinal fluid pressure, ensuring collateral vascular network stability and distal aortic perfusion and intrathecal administration of drugs. A multimodal approach involving anesthesiologists and surgeons can lead to improved neurological recovery and a reduced incidence and severity of SCI.

Full text

Monaco et al. Vessel Plus 2023;7:23
DOI: 10.20517/2574-1209.2023.113 Vessel Plus
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Open AccessReview
A multimodal approach to prevent spinal cord
ischemia in patients undergoing thoracoabdominal
aortic aneurism repair - from pathophysiology to
anesthesiological management
Fabrizio Monaco, Jacopo D'Andria Ursoleo, Gaia Barucco, Margherita Licheri, Carolina Faustini, Stefano
Lazzari, Ambra Licia Di Prima
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
Correspondence to: Dr. Fabrizio Monaco, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute,
Via Olgettina 60, Milan 20132, Italy. E-mail: monaco.fabrizio@hsr.it
How to cite this article: Monaco F, D'Andria Ursoleo J, Barucco G, Licheri M, Faustini C, Lazzari S, Di Prima AL. A multimodal
approach to prevent spinal cord ischemia in patients undergoing thoracoabdominal aortic aneurism repair - from
pathophysiology to anesthesiological management. Vessel Plus 2023;7:23. https://dx.doi.org/10.20517/2574-1209.2023.113
Received: 27 Aug 2023 First Decision: 26 Sep 2023 Revised: 6 Oct 2023 Accepted: 19 Oct 2023 Published: 27 Oct 2023
Academic Editors: Narasimham L. Parinandi, Paolo Nardi Copy Editor: Fangyuan Liu Production Editor: Fangyuan Liu
Abstract
Thoraco-abdominal aortic aneurysm (TAAA) open repair is a high-risk surgery further burdened with both
mortality and morbidity. Despite numerous experimental endeavors and technical advancements, spinal cord
ischemia (SCI) is still the most formidable morbidity to be resolved, irrespective of the open or endovascular
surgical approach. It presents a spectrum of severity, ranging from temporary or permanent paraparesis to
paraplegia with or without autonomic dysfunction. The timing of SCI occurrence is a crucial factor, with
approximately 15% of cases manifesting intraoperatively, 50% within 48 h post-surgery, and the remaining 35%
classified as late SCI, occurring more than 48 h after the procedure. The mechanism responsible for SCI is complex
and multifactorial; hence, understanding its underlying pathophysiology is essential for its effective management.
Over the last decade, strategies to enhance spinal cord perfusion and minimize the risk of SCI during TAAA open
repair have been implemented. These include optimization of hemodynamics, hemoglobin levels, cardiac function,
and cerebrospinal fluid pressure, ensuring collateral vascular network stability and distal aortic perfusion and
intrathecal administration of drugs. A multimodal approach involving anesthesiologists and surgeons can lead to
improved neurological recovery and a reduced incidence and severity of SCI.
Keywords: Thoraco-abdominal aorta aneurysm, spinal cord ischemia, aneurysm repair, anesthetic management,
aortic surgery, cerebrospinal fluid drainage, collateral network, partial left heart bypass, cardiac function

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INTRODUCTION
Spinal cord ischemia (SCI) is one of the most devastating complications in the repair of thoraco-abdominal
aortic aneurysms (TAAA) in both the open and endovascular approaches. When it occurs, it carries a poor
prognosis, leading to patients’ reduced quality of life, high complication and mortality rate, and prolonged
duration of intensive care unit (ICU) and hospital stays[1,2]. The incidence of SCI in the repair of TAAA
ranges between as low as 2%-3% and 10%, while the one-year survival of those who suffer this complication
is as low as 40%[3,4]. SCI encompasses a spectrum of severity that extends from temporary or permanent
paraparesis to paraplegia with or without autonomic dysfunction. SCI can manifest at various time points.
Approximately 15% of cases occur intraoperatively, meaning the injury takes place during the surgical
procedure. Around 50% of cases fall into the intermediate category, with symptoms manifesting within 48 h
following the procedure. The remaining 35% are classified as late SCI, with symptoms arising more than 48
h after surgery[5]. These timing distinctions reflect the underlying pathophysiology of SCI. Intraoperative
SCI is directly linked to the interruption of blood flow, while postoperative SCI is influenced by
hemodynamic management, particularly through the establishment and stabilization of the collateral blood
flow.
Intermediate paraplegia, which occurs within 48 h after surgery, is more insidious in nature. Its
development is intricately tied to the recruitment of the collateral network that is supplied by the
hypogastric and intercostal arteries, as well as branches of the subclavian artery. The management of SCI is
grounded in a deep understanding of its pathophysiology and requires a multimodal approach [Figure 1]. In
fact, multiple strategies are implemented for preventing and addressing SCI, including the placement of
cerebrospinal fluid (CSF) drainage, distal aortic perfusion, optimization of blood pressure, restoration of
blood flow in collateral network vessels, embolization and reimplantation of segmental arteries according to
the monitoring of motor (MEP) and somatosensory-evoked potentials (SSEP).
By employing these strategies, anesthesiologists and surgeons can work towards minimizing the occurrence
and severity of SCI and maximizing the chances of neurological recovery[6]. The present review discusses the
evolution of strategies that can be applied to maximize spinal cord perfusion and decrease the risk of SCI
during thoracoabdominal aortic aneurysm repair.
VASCULAR ANATOMY OF THE SPINAL CORD
The spinal cord (SC) vasculature consists of very small vessels running in intricate, three-dimensional
planes with substantial regional and inter-individual variability. SC vasculature was originally visualized
with routine contrast-enhanced CT scanning back in 1994, yet information about the SC circulation has, for
the most part, been gained from post-mortem studies. The first accurate anatomical descriptions were
provided in 1881 by Adamkiewicz and Kady. They described the vascular system of the SC as consisting of
one anterior and two posterolateral anastomotic trunks running longitudinally. Inflow vessels to the SC
include: the subclavian artery (through the vertebral artery), the thyrocervical trunk, and the costocervical
trunk; several segmental feeders from the intercostal and lumbar arteries; the hypogastric arteries (through
the lateral sacral and iliolumbar arteries). Arteries directly nourishing the SC (intrinsic arterial system) are
divided into two different systems: a central (centrifugal) system fed by the sulcal arteries; and a peripheral
(centripetal) system, the pial plexus (or pial network), which gives origin to perforating branches. The pial
network forms an impressive secondary anastomotic system along the entire length of the SC between the
anterior and posterolateral longitudinal vessels. The anterior spinal artery (ASA) is ultimately an
anastomotic channel between ascending and descending branches of neighboring anterior radicular arteries.

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Figure 1. The multimodal approach for SCI prevention is based on MAP, CVP and CSFP modulation. MAP: Mean arterial pressure; CVP:
central venous pressure; CSFP: cerebrospinal fluid pressure.
PATHOPHYSIOLOGY OF SPINAL CORD ISCHEMIA
Risk factors associated with spinal cord ischemia
A greater understanding of the anatomy and physiology of spinal cord perfusion has led to the recognition
of several risk factors associated with spinal cord ischemia (SCI). The extent of aortic replacement is the
most important predictor, with the highest rates observed for Extent II (10%-20% and Extent I TAAAs and
the lowest rates for Extent IV TAAAs (1%-5%))[7-9]. In addition, occlusion of the collateral network
(hypogastric and/or vertebral artery) is associated with a higher rate of immediate paraplegia and a lack of
improvement in motor function following remedial maneuvers[10]. Other determinants include prior aortic
replacement, chronic kidney disease, chronic obstructive pulmonary disease, and age[10,11].
Spinal cord collateral network
The artery of Adamkiewicz is a significant branch of a segmental artery (SA) found in the lower thoracic or
upper lumbar region, originating from T8-L1. It possesses a distinct hairpin turn and plays a crucial role in
supplying blood to the anterior spinal artery (ASA). In the treatment of extensive TAAAs, careful
identification and subsequent reimplantation of the SA have been considered the most effective strategy to
prevent severe neurological complications. However, the experience gained in endovascular treatment of
TAAAs has shown that SCI is a potentially avoidable outcome, even when there is a significant sacrifice of
the segmental arteries. This has led to a shift from the traditional anatomical paradigm, where the absence
of blood flow was considered synonymous with SCI, to a pathophysiological approach. As a consequence,
the need for a comprehensive understanding of spinal cord circulation is often overlooked, and the focus
shifted to hemodynamic and metabolic variables as the main determinants of SCI prevention. In this
approach, factors related to blood flow dynamics, such as blood pressure optimization and collateral vessel
recruitment, as well as metabolic factors affecting spinal cord tissue oxygenation and energy supply, are
considered crucial for preventing SCI. Lazorthes et al. detailed the multiple vessels that contributed to the
spinal cord blood supply and first implemented Adamkiewicz’s original anatomical observations[12]. They

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described the existence of a rich collateral pathway of vessels in both the perivertebral space and alongside
paraspinal muscles that anastomose outside the spinal canal, generating the spinal cord collateral network.
It consists of an axial network of small arteries in the spinal canal, perivertebral tissues, and paraspinal
muscles that anastomose with each other and with the nutrient arteries of the spinal cord. Inputs come from
segmental, subclavian, and hypogastric arteries and their branches (originating from the internal iliac artery,
namely the iliolumbar artery and lateral sacral arteries). Hence, the blood supply to the spinal cord can be
either increased from one source when another is reduced or decreased when a low-resistance pathway is
opened, leading to the steal phenomenon. This event is discernible and becomes apparent when utilizing an
aortic cross-clamp in the thoracic district while incising the aneurysmal thoracic aorta, as noted by
Christiansson and colleagues. Such action establishes a gradient between the spinal cord and the aorta,
causing retrograde bleeding from the intercostal arteries into the exposed aorta. As a result, this impacts the
spinal cord perfusion pressure (SCPP) and can potentially lead to anemia and hemodynamic instability[13].
Hence, there is the need to limit the back-flow from the intercostal arteries by the rapid insertion of
occlusive pegs, balloons, and tourniquets in the segmental vessels within the aorta. In particular,
Griepp et al. employed a method in which they clamp and divide the segmental vessels entering the aorta
within the segment to be excised prior to cross-clamping or opening the aorta, which resulted in a 2%
incidence of paraplegia[14]. As virtually all clinical approaches to thoracic and thoracoabdominal aneurysm
resection unavoidably entail periods of cord ischemia, the importance of meticulous monitoring of
perfusion variables has become crucial to ensure sufficient blood flow through the spinal cord collateral
network.
Mechanisms of injury
From a pathophysiological perspective, an imbalance between oxygen demand and delivery (DO2) at the
spinal cord level following interruption of blood flow in the intercostal arteries during thoracic aortic
surgery causes SCI. Thoracic aorta cross-clamping leads to a reduction in perfusion pressure to the vascular
network supplying the central nervous system (CNS). Consequently, clamping time plays a pivotal role in
the development of ischemia since its lengthening triggers cellular and molecular alterations (e.g., shift from
aerobic to anaerobic metabolism), which in turn result in local and systemic alterations, ultimately leading
to ischemia. Noteworthy, the combination of both a direct (interruption of blood flow) and an indirect
effect which is in addition to the former (derived from the production of oxygen free radicals, lipid
peroxidation, intracellular calcium accumulation, leukocyte activation, inflammatory response) ultimately
results in neuronal apoptosis. More specifically, since visceral tissues in the district distal to the aortic clamp
shift from an aerobic to an anaerobic metabolism, lactates are produced and cellular membranes increase
their permeability, resulting in cellular swelling. Furthermore, the production of reactive oxygen species
(ROS) and nitric oxide (NO) coupled with lipid peroxidation suppress adenosine triphosphate (ATP)
synthesis, inactivate homeostatic metabolic enzymes, deplete antioxidant reserves, disrupt cellular and
mitochondrial membranes and further boost the phenomenon of apoptosis by means of intracellular
electrolytes derangement[15]. All these factors acting simultaneously lead to the destruction of the blood-
spinal cord barrier, with spinal cord edema, increased leukocyte infiltration, amplification of inflammation,
and oxidative stress[16]. Even reperfusion, causing inflammation, hyperemia, and edema, worsens overall
cellular damage and contributes to an irreversible clinical presentation of paraplegia. In daily clinical
practice, interrupting blood flow to the spinal cord does not always result in the development of SCI.
Furthermore, while reimplantation of intercostal arteries during TAAA repair is desirable, it is not always
feasible. Therefore, it might be plausible to replace an “anatomical paradigm” where sacrificing the
intercostal arteries inevitably leads to spinal cord ischemia with a “pathophysiological” paradigm, in which
spinal cord circulation is essentially ignored, and cardiac function, systemic arterial perfusion, DO2, and
cellular metabolism become the therapeutic targets to prevent neurological damage [Table 1].

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Table 1. Physiologic determinants, target values and potential therapeutic interventions to avoid spinal cord ischemia (SCI) during
thoracoabdominal aortic aneurysms (TAAA) repair
Determinant Target value Potential therapeutic intervention
MAP 85-100 mmHg • Increase volemia
• Vasoactive drugs infusion
• Reduce clamping time
• Gradual clamp release
• Avoid abrupt pressure variations
CSFP 8-10 mmHg Place external CSF drainage
CVP < 10 mmHg • Implement diuretic therapy
• If RV dysfunction is present:
Optimize gas exchange by increasing FiO2
Moderate hyperventilation
Dobutamine/adrenaline infusion
DO21,000 mL/min • Improve SaO2
• Keep Hb > 10 g/dL
• Ensure CI > 2.5 L/min
Body temperature 32-34 °C • Mild hypothermia
• 300 mL cold saline infusion in each of the renal arteries
• Cold saline infusion with dual-lumen catheter in epidural space
MAP: Mean arterial pressure; CSFP: cerebrospinal fluid pressure; CSF: cerebrospinal fluid; CVP: central venous pressure; RV: right ventricular;
FiO2: inspired fraction of oxygen; DO2: oxygen delivery; SaO2: arterial oxygen saturation; Hb: hemoglobin; CI: cardiac index.
PERIOPERATIVE MONITORING OF SPINAL CORD ISCHEMIA
Open TAAA surgery benefits from intraoperative neurophysiological monitoring (IONM) for the
identification of SCI. Descending and ascending spinal pathways are evaluated by means of motor (MEPs)
and somatosensory evoked potentials (SSEPs), respectively. SSEPs are elicited by stimulation of posterior
tibial nerves at the ankle and/or median nerves using subdermal needle electrode pairs. Similarly, MEPs are
elicited in the upper extremities with a needle electrode in the abductor pollicis brevis or the first dorsal
interosseus muscle and both tibialis anterior and abductor hallucis muscles in the lower ones. Limitations of
neurophysiologic monitoring include the inability to differentiate between medium and severe SCI and that
it can be influenced by lower limb ischemia resulting from vascular introducers[17].
Anesthetic agents
Anesthesia shows a profound influence on evoked potentials. Volatile anesthetics reduce the amplitude of
SSEP, increase their latency, and impair cortical waves; hence, their administration should not exceed 0.5
MAC[18,19]. Intravenous anesthetics (e.g., propofol and remifentanil infusions), combined with low
concentrations of volatile anesthetic agents if appropriate, represent the first line of choice when the
monitoring of evoked potentials is in place[20].
Neuromuscular blockers
Careful attention must also be given to the administration of neuromuscular blockers to safeguard
appropriate muscle relaxation and an adequate response of MEPs. IONM also proved to be beneficial for
categorizing patients based on their risk of SCI when the vascular phase of surgery is over. Bianchi et al.
used a multimodal IONM approach, combining MEP, SEP, and peripheral nerve monitoring techniques in
100 consecutive patients undergoing TAAA open repair[21]. The study showed a notably higher rate of
immediate postoperative motor deficits consistent with SCI, particularly in cases with irreversible MEP
deteriorations compared to reversible ones. The authors concluded that implementing a multimodal IONM
protocol could improve MEP interpretation and assist surgeons in making informed decisions before
concluding vascular maneuvers. Although IONM has the potential to detect SCI during surgery, during the
timeframe between the end of the surgical procedure and the subsequent neurological clinical evaluation,
limited information about the presence of SCI is available for clinicians. In order to address this gap, von

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Aspern et al. have employed collateral network near-infrared spectroscopy (cnNIRS)[20]. By monitoring the
perfusion of the paraspinal muscles at both thoracic and lumbar levels, cnNIRS can serve as an indirect
measure of the perfusion of the spinal cord collateral network by assessing its oxygenation patterns[22].
Nevertheless, NIRS still lacks clinical validation in this setting and its routine utilization is not yet
recommended[23,24].
ANESTHESIOLOGIC STRATEGIES
The main objective of anesthesia management is to avoid abrupt hemodynamic changes that can critically
reduce spinal cord perfusion. The main factors that alter hemodynamics in patients undergoing TAAA are:
cardiac function, the level of aortic clamping, hemoglobin levels, distal aortic perfusion with partial left
heart bypass (PLHB) circulatory assistance, patient’s body temperature, intrathecal administration of
medications and cerebrospinal fluid (CSF) pressure. Hence, by acting on the above-mentioned factors, a
goal-directed hemodynamic strategy is mandatory for the anesthesiologist to achieve adequate spinal cord
oxygenation and perfusion.
It is logical to think that mean arterial pressure (MAP) serves as the driving pressure, and higher values of
systemic pressure lead to a lower risk of paraplegia. However, it is not the MAP as an “absolute value” that
reduces the risk of paraplegia but the difference compared to its preoperative baseline value[5]. For instance,
patients with a preoperative history of hypertension require significantly higher MAP during the
perioperative period compared with normotensive patients. Within this pathophysiological approach to
spinal cord perfusion, central venous pressure (CVP) also plays a quintessential role[5]. Indeed, the outflow
from the spinal cord relies on the systemic venous pressure and therefore the CVP. Since the vertebral
venous plexus is functionally a large single plexus with high-capacity vessels that extend along the entire
spinal cord, an increase in CVP is associated with increased pressure in the vertebral venous plexus. As the
spinal canal is a non-expandable space, increased pressure in the vertebral plexus directly causes an
elevation of cerebrospinal fluid pressure (CSFP). The effect of elevated CVP is irrelevant when
vascularization is intact but is crucial in cases of extensive sacrifice of intercostal arteries. In their experience
with monitoring of MEP and SSEP during repair of TAA/A in 100 consecutive patients in whom spinal
cord artery reattachment was (with 1 exception) not carried out, Etz et al. reported that spinal cord
perfusion proved to be profoundly unstable under the above-mentioned conditions, with spinal cord
perfusion pressure (SCPP), defined by the difference between mean arterial pressure distal to clamp
(MAPd) and CSFP, being around 20 mmHg in the hours and days following surgery[25]. With such a low
driving pressure value, elevated CVP can significantly increase CSFP and reduce spinal cord outflow,
leading to SCI. Because spinal arteries cross the vertebral venous plexus, congestion of this plexus,
secondary to high cardiac preload, exhibits a compressive effect on the segmental arteries that nourish the
spinal cord.
Cardiac function
Cardiac function is the main determinant of MAP and CVP, which in turn are modulated by the right (RV)
and left ventricle (LV). Transesophageal echocardiography allows for early identification of right and left
heart dysfunction and its determinants (preload, contractility, or afterload).
Right ventricular dysfunction
Right ventricular (RV) dysfunction is one of the causes of CVP elevation; hence, cardiac function must be
constantly monitored and supported in the event of a decline in performance. Echocardiographic criteria of
RV dysfunction are summarized in Table 2.

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Table 2. Overall view of the main echocardiographic criteria of right and left ventricular (RV and LV, respectively) dysfunction
Criteria of ventricular dysfunction
Right (RV) Left (LV)
RVFAC < 30%
Tricuspid annular plane systolic excursion < 16 mm
Tissue Doppler index < 10 cm/s
RV/LV > 0.6
PAOP > 15 mmHg
EF < 50%
LVOT VTI < 20 cm/s with good RV function
RVFAC: Right ventricular fractional area change; RV/LV: right ventricular to left ventricular diameter ratio; PAOP: pulmonary artery occlusion
pressure; EF: ejection fraction; LVOT VTI: left ventricular outflow tract (LVOT) velocity time integral (VTI); RV: right ventricular.
The RV is particularly sensitive to increased pulmonary resistance from vasoconstriction secondary to
hypercapnia, hypoxia, acidosis, and polytransfusion. Therefore, the first-line treatment of RV dysfunction is
the optimization of gas exchange with a high fraction of inspired oxygen (FiO2) and moderate
hyperventilation.
When moderate pulmonary hypertension (Tricuspid Annular Plane Systolic Excursion [TAPSE] > 16 mm
or Tissue Doppler Imaging [TDI] > 10 cm/s and Pulmonary artery systolic pressure [PAPs] > 30 mmHg)
with preserved systolic function (ejection fraction [EF] > 60%) and low preload (CVP < 10 mmHg) occurs,
fluid challenge is recommended. High CVP (> 15mmHg) should be treated aggressively with diuretic
therapy. Poor RV contractility (TAPSE < 16 mm or TDI < 10 cm/s) may be associated with poor inotropism
secondary to pre-existing coronary artery disease (CAD), and myocardial hypoperfusion due to low
coronary artery gradient from left-sided dysfunction.
In cases of moderate RV dysfunction, dobutamine infusion is the first-line treatment. Adrenaline is
indicated in cases of biventricular dysfunction, hypotension, or severe RV dysfunction. In patients with RV
failure and low pulmonary vascular resistance but no pre-existing pulmonary hypertension, norepinephrine
is effective in maintaining adequate coronary perfusion pressure (CPP). Therapeutic targets are summarized
in Figure 2.
Left ventricular dysfunction
LV function is equally of paramount importance in preventing SCI. The development of low cardiac output
syndrome (LCOS) with refractory and prolonged hypotension has catastrophic effects on spinal cord
perfusion. Early recognition and treatment can mitigate its effects. The criteria for LV dysfunction are
summarized in Table 2.
In particular, reduced ejection fraction (EF < 50%) in the postoperative period due to ischemic events or the
onset of supraventricular arrhythmias is a relatively frequent cause of hypotension during the days following
surgery, and may be a direct cause of the development of SCI[26].
The presence of atrial fibrillation (AF) is associated with prolonged hospitalization, higher in-hospital
mortality, and reduced mid-term survival[27]. As observed by Coselli et al. in a series of more than 1,000
patients undergoing type II TAAA, the presence of preoperative CAD is one of the main predictors of SCI
on multivariate analysis, increasing the risk of paraplegia in the postoperative period by 80%[26].
With regard to treatment, the evaluation of myocardial contractility and wall motion abnormalities should
be conducted following preload optimization. Poor contractility is managed with adrenaline and
dobutamine infusion. MAP is also critical in regard to coronary perfusion; in fact, it is not uncommon to
observe MAP-dependent ST abnormalities.

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Figure 2. Main therapeutic targets and decision-making algorithm in the occurrence of right ventricular (RV) dysfunction. RV: Right
ventricular; CVP: central venous pressure.
If increased afterload is associated with systolic ventricular dysfunction, infusion of inodilators is indicated.
Conversely, increased afterload associated with normal systolic contraction benefits from the use of short-
acting vasodilators. The therapeutic targets are summarized in Figure 3.
Aortic clamping
Pressure changes can be extreme during clamping, yielding different effects on systemic blood pressure
depending on the level of aortic clamping[28].
In particular, if the clamping occurs at the supraceliac level, blood is displaced from the vascular bed distal
to the aortic clamping to that proximal to the clamping, due to decreased venous capacitance and the
venoconstrictor effect exhibited by catecholamines[29]. Conversely, if the clamping is subceliac, the blood
moves into the splanchnic circulation, causing a decrease in cardiac preload if the splanchnic venous tone is
low, or an increase in preload if the venous tone is high[30]. The increase in preload and afterload as a result
of aortic clamping leads to an increase in cardiac contractility and cardiac output[29].The increase in left
ventricular end-systole (LV ESP) and end-diastole pressure (LV EDP) as a result of increased aortic
impedance leads to transient subendocardial ischemia that stimulates increased coronary flow and
contractility (ARPNER’s effect)[31]. If coronary flow reserve (CFR) is poor (e.g., due to pre-existing coronary
artery disease), the patient will not be able to increase coronary flow, resulting in low flow, cardiac ischemia,
and systemic hypotension, which correlate with an increased risk of SCI.
An early etiological diagnosis with intraoperative transesophageal echocardiography makes it possible to
distinguish whether the hypotension is caused by hypovolemia, cardiac dysfunction, or peripheral
vasodilatation[32]. Based on this, it may be indicated to administer vasodilators to reduce afterload, preload
and induce coronary vasodilation, to increase cardiac contractility with inotropic drugs, or simply to expand
the blood volume with fluids in the case of reduced preload.
At the time of declamping, because of volume redistribution in the lower limbs and wash-out of vasoactive
and myocardial-depressor metabolites from the ischemic areas, hypotension sets in, resulting in central
hypovolemia and reduced cardiac output[28]. At this stage, the risk of SCI is particularly high due to the

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Figure 3. Main therapeutic targets and decision-making algorithm in the occurrence of left ventricular (LV) dysfunction. LV: Left
ventricular; CVP: central venous pressure; RWMA: regional wall motion abnormalities.
decrease in SCPP secondary to decreased MAP and active bleeding. Hypotension following declamping can
be corrected through various means, including increasing blood volume, infusing vasoactive drugs,
reducing the clamp time, or employing a gradual release of the clamp. Rapid treatment of metabolic
alterations may prove useful.
Partial left heart bypass
To date, partial left heart bypass (PLHB) is considered the best technique to reduce ischemia time in tissues
vascularized by arteries originating downstream of the aortic clamp, to support left ventricular function and
to control hypertension during TAAA correction surgery[33].
Dynamic use of PLHB makes it possible to modulate the perfusion pressure in the district proximal and
distal to the clamp by keeping it between 85 mmHg and 100 mmHg for the whole duration of the surgical
procedure and ensuring adequate SCPP. If the MAP falls below 60 mmHg, the perfusion pressure in the
collateral medullary network is proportionally reduced. The use of PLHB has been associated with a
reduced risk of paraplegia[34]. Safi et al. report that the use of PLHB in patients undergoing TAAA repair also
improves the outcome in Crawford type I and II by reducing the risk of paraplegia when used in
combination with CSF drainage[35]. Furthermore, although heparin is routinely administered to prevent
intraoperative thrombosis, when PLHB is used, a higher degree of anticoagulation compared with the
“clamp-and-go” technique is required. This may eventually worsen both the underlying TAAA-related
coagulopathy and bleeding.
Cerebrospinal fluid drainage
Cerebrospinal fluid (CSF) drainage is the most effective procedure in preventing SCI after aortic repair[36].
The pathophysiological rationale behind the use of CSF drainage is the need to lower cerebrospinal fluid
pressure (CSFP) by increasing SCPP. In light of this, the use of CSF drainage has entered clinical practice.
CSF drainage positioning was found to significantly reduce the risk of paraplegia in a randomized
controlled trial of 145 patients undergoing extent I and II TAA surgery[37]. These data are further supported
by clinical practice. The use of CSF drainage as a rescue in patients who have developed neurological deficits
following surgical interventions is able to reverse paraplegia and paresis by decreasing the CSFP. Hence, its
use has become an essential tool in the multimodal approach for the prevention of SCI, in combination with
the above-mentioned hemodynamic optimization strategies. Preventing catheter obstruction and deflecting
any complications may be achieved by continuous monitoring of CSFP, even if this procedure carries its

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own risks and complications. The risk of developing subarachnoid hemorrhage due to excessive loss of CSF
in a short time is lower with intermittent CSF drainage compared to continuous CSF drainage. Meningitis
(0.1%), subdural hematoma (1.7%), and intracranial hemorrhage (1.8%) are the most severe
complications[38], while subdural hematoma is associated with excessive CSF drainage and tearing of the
dural veins. A CSF pressure ≥ 10 mmHg is recommended in the absence of ischemia or to perform an
intermittent drainage of 10-20 mL/h with continuous systemic blood pressure monitoring. Patients with
cerebral atrophy, arteriovenous malformations, brain aneurysms, and a history of previous subdural
hematoma are particularly prone to developing cerebral hemorrhage[39].
Anemia
Monitoring of hemoglobin levels is particularly relevant as it directly affects DO2. In situations where
cardiac output is suboptimal, maintaining maximum arterial oxygen saturation and hemoglobin levels
above 10 g/dL can be beneficial[40]. The combination of bleeding, anemia, and hypotension can worsen SCI.
A decrease in the oxygen content of arterial blood (CaO2) leads to a reduction in the ratio of DO2 to oxygen
consumption (VO2) < 2. When DO2 falls below this threshold, VO2 becomes dependent on DO2, leading to a
shift from aerobic to anaerobic metabolism, resulting in lactate production and metabolic acidosis. Thus, it
is crucial to manage bleeding by ensuring meticulous surgical hemostasis and employing viscoelastic tests.
Studies have shown that the use of rotational thromboelastometry significantly reduces the need for fresh
frozen plasma (FFP) administration. Reduced FFP usage is associated with less hemodilution and anemia,
which can help mitigate the negative effects on oxygen delivery and prevent further complications of SCI[41].
Hypothermia
Several experimental studies have demonstrated the protective effect of mild hypothermia on the prevention
of SCI by reducing both nerve tissue metabolism and the release of excitatory neurotransmitters[42]. This
constitutes the pathophysiological rationale for the use of regional hypothermia during aortic clamping[43].
Cambria et al. report a protective effect of regional hypothermia of the spinal cord through epidural cooling
when it is used in combination with CSF drainage and intercostal artery repletion[44]. Shimizu et al. confirm
these findings but propose the use of a double-lumen catheter inserted into the peridural space into which
cold saline is infused[45].The risk of inserting a catheter of significant size (16 gouges in diameter and 30 cm
in length) into the peridural space, together with disputed scientific evidence, has ultimately limited the use
of techniques for regional cooling of the medulla to local experience.
Intrathecal drugs
Intrathecal administration of different drugs has led to inconclusive results so far. Lima et al. reported that
in 330 patients undergoing TAAA surgery, the addition of 30 mg of papaverine 1% intrathecally 10 min
before aortic clamping exhibited neuroprotective effects[46]. The rationale is its vasodilatory effect on the
arterial circulation, which would increase blood flow to the spinal cord. However, its short duration of
action and the risk of hypotension associated with possible systemic reabsorption have limited its use over
time. Other authors have proposed the use of naloxone, which would have a neuroprotective effect by
decreasing the level of endorphins released during SCI[47]. In particular, Acher et al. observed a significant
reduction in SCI in the 49 patients in whom naloxone was used in conjunction with CSF drainage[47]. Other
drugs such as calcium antagonists, N-methyl-d-aspartate, and edaravone were in animal models, but none
have provided results convincing enough to be implemented in clinical trials[48,49].
CONCLUSION
TAAA repair carries substantial perioperative risks, with spinal cord ischemia being the most common
complication leading to paraplegia. Therefore, each scheduled surgery case requires thorough discussions
between surgeons and anesthesiologists to carefully weigh the benefits and risks specific to the patient’s

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14
Figure 4. Multimodal therapeutic algorithm to treat spinal cord ischemia. CSF: Cerebrospinal fluid; CSFP: cerebrospinal fluid pressure;
SpO2: peripheral capillary oxygen saturation; Hb: hemoglobin; MAP: mean arterial pressure; CVP: central venous pressure; CI: cardiac
index; BSA: body surface area; SCPP; spinal cord perfusion pressure.
situation. Several strategies (e.g., perfusion, metabolism, and oxygen delivery to the spinal cord) can be
employed to mitigate the risk of spinal cord ischemia. These are based on acknowledging the most
important factors in protecting the spinal cord during and after thoracic and thoracoabdominal aortic
replacement, both when spinal cord blood flow is significantly reduced and after aortic replacement, while
the co-axial collateral network is recruited to restore resting blood flow to near-normal levels. The
anesthesiologist must ensure adequate spinal cord perfusion by elevating MAP within the range of
90-100 mmHg to promote spinal cord collateral network circulation and reduce CSFP through CSF
drainage. Cardiac output should be maximized to ensure adequate DO2 and CVP should be reduced to < 10
mmHg to avoid a significant increase in CSFP and reduced spinal cord outflow. In addition, Hb levels > 10
g/dL should be maintained, hypoxia and hypercapnia are to be avoided, and arrhythmias (e.g., tachycardia,
which can increase myocardial oxygen demand, ventricular wall tension, and overall myocardial work)
should be prevented and treated. Nonetheless, in the case of SCI occurrence, various strategies can be
implemented as well, involving a thorough and multimodal approach that focuses on CSF drain status, O2
delivery, and comprehensive hemodynamic management, as summarized in Figure 4. By fulfilling the
aforementioned objectives, anesthesiologists can optimize cardiac function and promote favorable
outcomes in patients undergoing TAAA open repair.
DECLARATIONS
Authors’ contributions
Designed the work, drafted the manuscript and revised it critically: Monaco F
Designed the work, collected and analyzed the data and drafted the manuscript: D’Andria Ursoleo J
Collected and analyzed the data and revised the manuscript critically: Barucco G, Licheri M, Faustini C,
Lazzari S
Collected and analyzed the data and drafted the manuscript: Di Prima AL
All authors gave final approval of the version to be published and agree to be accountable for all aspects of
the work in ensuring that questions related to the accuracy or integrity of any part of the work are
appropriately investigated and resolved.

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14
Availability of data and materials
Not applicable.
Financial support and sponsorship
None.
Conflicts of interest
All authors declared that there are no conflicts of interest.
Ethical approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Copyright
© The Author(s) 2023.
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