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\begin{document}

\title{Antegrade Versus Retrograde Cerebral Perfusion for Ascending Aorta and
Aortic Arch Replacement: Literature Review}



\author[1]{Ahmed Alnajar}%
\author[2]{Elizabeth Aleong}%
\author[3]{Muhammad  Azhar }%
\author[1]{Ryan Azarrafiy}%
\author[1]{Joseph Lamelas}%
\affil[1]{University of Miami Miller School of Medicine}%
\affil[2]{University of Florida}%
\affil[3]{Florida International University}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Aortic arch and hemiarch surgery necessitate the temporary interruption
of blood perfusion to the brain. Despite its complexity, hemiarch and
ascending aortic surgery can be performed via a minimally invasive
approach. Due to the higher risk of neurological injury during
circulatory arrest, several techniques were developed to further protect
the brain during this surgery. We searched the Embase, Medline, and
Cochrane databases and identified articles reporting outcomes of
antegrade and retrograde cerebral perfusion strategies. Herein, we
outline surgical approaches, intra-operative technical considerations,
and clinical outcomes of hemiarch and ascending aortic surgery.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Neurologic injury has been a major concern in cardiac surgery due to the
atherosclerotic burden in the vasculature, cross clamping, and the use
of extracorporeal circulation, leading to a significant increase in
morbidity, mortality, and cost.\textsuperscript{1-3} Furthermore,
disrupting blood flow to the brain will compound on the potential for
neurologic complications. The first documented aortic replacement dates
back to the 1950s with Denton A. Cooley, Michael DeBakey, and E. Stanley
Crawford.\textsuperscript{4} In both 1951 and 1955, aortic arch
replacements with the use of bypass shunts and moderate hypothermia were
fraught with failure. Only after DeBakey's concept of an early form of
antegrade cerebral perfusion in 1957, did surgeons successfully enter a
new era of aortic surgery. This was followed by Griepp's introduction of
total circulatory arrest under deep hypothermia (up to 14 \selectlanguage{ngerman}°C) in
1975.\textsuperscript{5-7} With these advances, the risk of stroke and
mortality with aortic surgery has greatly improved over the past 70
years. The main strategies that exist today to mitigate the risk of
brain injury include deep hypothermic circulatory arrest (DHCA),
antegrade cerebral perfusion (ACP), retrograde cerebral perfusion (RCP),
as well as a hybrid approach.\textsuperscript{8} The choice in cerebral
protection is dependent upon the surgeon's preference and experience
with a specific technique, so it is important to recognize the potential
advantages or disadvantages of each strategy.

\textbf{Brain protection strategies}

Dating back to the 1970s, the DHCA strategy works by reducing
injury-inducing pathways by lowering the cerebral
metabolism.\textsuperscript{9} The body is usually cooled to
temperatures of 20ºC or greater. Longer times of DHCA have been
correlated to an increased rate of neurological dysfunction, as
described by Yan and colleagues (Fig. 1),\textsuperscript{10} so there
is usually a need for the use of additional cerebral protection
strategies (ACP and RCP). RCP requires connecting the arterial tubing to
a cannula placed in the superior vena cava (SVC) and then reversing
blood flow to the brain in a retrograde fashion. This approach has been
successful in reducing both mortality and morbidity.\textsuperscript{11}
An advantage of this strategy is that it provides cold retrograde blood
flow to the brain during DHCA and therefore allowing for a decreased
risk of embolization.\textsuperscript{12}Moderate hypothermic
circulatory arrest (MHCA) with temperatures ranging from 24ºC to 28ºC
can be combined with selective ACP.\textsuperscript{13} Once circulatory
arrest is established, one or multiple arch vessels are cannulated and
perfused with cold blood in an antegrade fashion. Some studies have
suggested that ACP leads to better neurological outcomes when compared
with RCP.\textsuperscript{14}The debate between RCP and ACP has been
ongoing since the 1990s. Despite the fact that RCP has proven to be
effective, many surgeons still prefer using ACP.\textsuperscript{15} RCP
neuroprotective effects are explained by its continuous cerebral
cooling, and not from antegrade nutritive blood
flow.\textsuperscript{16} RCP's efficacy may also be reduced by the
presence of venous valves that require an elevated perfusion pressure,
which could cause increase intracranial pressure and subsequently worsen
neurological outcomes.\textsuperscript{17} However, RCP does not require
exposure or manipulation of the aortic arch vessels, whereas ACP
requires insertion of a catheter into the arch vessels, vessel clamping
or snaring; which can increase the potential of vessel injury or
embolization. Nonetheless, there has not been a clinical study
demonstrating that one approach is superior to the
other.\textsuperscript{18} RCP provides improved exposure of the arch
vessels, although there is a constant flooding of venous blood return
into the operative field, whereas ACP yields a dryer field with
catheters potentially obscuring visibility.

\textbf{Surgical techniques}

\textbf{1. Antegrade cerebral perfusion}

Antegrade cerebral perfusion can be safely achieved unilaterally through
the innominate or right common carotid artery, as well as combined with
the left common carotid artery to achieve bilateral ACP. When comparing
unilateral and bilateral ACP, most published series quote use of
unilateral ACP only if adequate collateralization is demonstrated
through backflow from the contralateral carotid artery or if
contralateral perfusion is evident by near-infrared spectroscopy
(NIRS).\textsuperscript{4} Bilateral ACP may be more advantageous when
considering existing conditions such as arterial stenosis, stroke, and
other vascular anomalies. Many surgeons prefer bilateral ACP to ensure
bihemispherical perfusion due to its documented efficacy and safety
beyond 40-50 mins of circulatory arrest.\textsuperscript{19}Alternative
cannulation strategies can be utilized to establish antegrade cerebral
perfusion. A prosthetic graft can be anastomosed to the right
subclavian, innominate, or right common carotid artery. Additionally,
balloon occlusion perfusion catheters can be utilized to provide
antegrade cerebral perfusion without vessel clamping or snarring.
Peripheral cannulation of the axillary artery can be performed to
establish cardiopulmonary bypass and subsequent ACP with concomitant
insertion of a balloon occlusion perfusion catheter into the carotid
artery without directly cannulating supra-aortic
vessels.\textsuperscript{4}

\textbf{2. Retrograde cerebral perfusion}

Retrograde cerebral perfusion takes a different approach as cold
oxygenated blood is delivered retrograde through a cannula placed in the
superior vena cava.\textsuperscript{19} After the patient is cooled to
achieve deep hypothermia and circulatory arrest established, RCP can be
employed. If a bicaval venous cannulation technique is employed for
cardiopulmonary bypass, Y-connectors with limbs are utilized to connect
the arterial to the venous lines. These limbs are clamped during the
conduct of cardiopulmonary bypass. When beginning to initiate retrograde
cerebral perfusion, the SVC cannula is snared and the limb connecting
the arterial cannula to the SVC cannula is
unclamped.\textsuperscript{20} This enables cold blood to run retrograde
into the SVC to perfuse the brain (Fig. 2). A cardiotomy suction is
placed in the open thoracic aorta to suction the blood return from the
arch vessels.\textsuperscript{21} Ice packs are also placed on the scalp
of the patient for additional topical brain cooling. RCP, as well as
ACP, has been historically performed via a median sternotomy, upper
hemisternotomy, or other partial sternal splitting variations. However,
currently, RCP is the only cerebral protection strategy that can be
employed through a right mini-thoracotomy minimally invasive ascending
aorta and hemiarch surgery.\textsuperscript{22}A hybrid approach to
these techniques include utilizing 2 separate heater coolers, one for
the systemic circulation and one for the cerebral circulation. With this
approach, the right carotid artery is exposed in the neck or the
innominate artery is exposed from within the chest. Each vessel is
directly cannulated and clamped with perfusion coming from a separate
tubing connected to the heart lung machine with its own respective
heater cooler. Since there are 2 heater coolers, perfusion to the brain
can be maintained at 10 degrees C, while perfusion of the body can
remain a mild to moderate hypothermia (28 degrees C). This not only
allows continuous brain perfusion, but avoids the potential coagulopathy
associated with systemic hypothermia.

\textbf{Discussion}

Improvements to cerebral protection strategies have enabled longer
circulatory arrest times when compared to DHCA alone, which limits the
safe circulatory arrest time to only 30 minutes.\textsuperscript{18} By
incorporating ACP and RCP into the cerebral protection strategy, stroke
and mortality rates have been reduced. Although using MHCA with ACP has
been the primary neuroprotective strategy in many high-volume aortic
centers worldwide, the question of which strategy provides better
outcomes in ascending aorta, hemiarch or arch replacement remains an
area of significant controversy and debate. Thus, several studies have
attempted to answer which cerebral protection strategy offers the best
patient outcomes (Table 1). In a prospective study, Abdelgawad and
colleagues demonstrate excellent results utilizing MHCA with ACP.
Although, these results were comparable to those of DHCA with RCP. ACP
was correlated with both shorter clamp and ischemic times with no
statistically significant difference in mortality and stroke
rates.\textsuperscript{23} Other studies have also advocated for ACP as
the strategy of choice. In a 2008 study, Apostolakis and colleagues
investigated outcomes in 48 patients undergoing urgent aortic surgery
for type A dissection. Their results concluded that ACP had a lower rate
of stroke, earlier extubation, shorter ICU stay, and reduced
costs.\textsuperscript{24} Wiedemann and colleagues analyze 329 patients
undergoing aortic surgery for type A dissection and also found ACP to be
associated with better short and long-term survival
rates.\textsuperscript{25}However, several studies suggest RCP with DHCA
to be equivalent, if not better, to ACP with MHCA. In a prospective,
randomized study of 20 patients undergoing hemiarch replacement,
Leshnower and colleagues used magnetic resonance imaging (MRI) to
evaluate the incidence of brain injury. Despite no significant
difference in clinically evident neurologic injury between patient who
had MHCA with ACP and DHCA with RCP patients, the former had a higher
incidence of radiographic neurologic injury (n=9,100\% vs n=5, 45\%;
p=0.01).\textsuperscript{26}Moreover, an STS database analysis of 7353
patients found that retrograde cerebral perfusion demonstrated a low
risk of acute stroke in patients who underwent type A dissection
repair.\textsuperscript{27}The literature is further obscured by
multiple studies advocating one technique over the other. A large
Society of Thoracic Surgeons database analysis evaluated 7830 patients
undergoing hemiarch or total arch replacement from 2014 to 2016. The
study excluded aortic dissections from the analysis. It concluded that
in patients requiring more than 30 minutes of circulatory arrest,
optimal strategies for cerebral protection include deep hypothermia with
either antegrade or retrograde cerebral perfusion, or moderate
hypothermia with antegrade cerebral perfusion.\textsuperscript{28} This
conclusion essentially suggests that either strategy is acceptable as
long as some form of cerebral perfusion is used. Furthermore, in a large
study of 4,128 patients undergoing ascending aortic repair for Type A
dissection in Japan, RCP had similar results in both mortality and
neurologic outcomes when compared to ACP.\textsuperscript{29}Recently,
minimally invasive surgical techniques have been applied to replacement
of the ascending aorta and hemiarch at experienced centers. The majority
of minimally invasive procedures reported are performed via an upper
hemisternotomy (Fig. 3).\textsuperscript{30-32} In a mini-thoracotomy
approach, cerebral perfusion is exclusively performed via
RCP.\textsuperscript{33} The initial outcomes of the first reported
minimally invasive, right mini-thoracotomy replacement of the ascending
aorta and aortic valve in 20 patients was excellent; with no strokes,
reoperations for bleeding, conversions to sternotomy or 30-day
mortality.\textsuperscript{34} In 2018, Lamelas and colleagues further
described their experience with a sternal-sparing replacement of the
ascending aorta with or without a concomitant aortic valve replacement
via a right mini-thoracotomy in 74 patients. A propensity score-matched
analysis was performed between 63 patients undergoing a sternotomy and
an equivalent number of patients undergoing a minimally invasive
non-sternotomy approach. The 30-day mortality was 3.2 \% in both groups,
while stroke incidence was 0\% in the minimally invasive group and 1\%
in the sternotomy group. Despite a longer circulatory arrest times in
the minimally invasive group, stroke rate, as well as the transfusion
requirements, ventilation times, as well as the ICU and hospital stays
were less than the sternotomy group.\textsuperscript{35}

\textbf{Conclusions}

The literature regarding the preferential use of antegrade versus
retrograde cerebral perfusion during aortic surgery remains
controversial. Analysis of many large databases in thoracic surgery have
yielded excellent results for both cerebral protection strategies. The
minimally invasive hemisternotomy or right mini-thoracotomy approach to
replacement of the ascending aorta has also demonstrated excellent
results. Future studies will be needed to compare sternotomy and
minimally invasive approaches utilizing both antegrade and retrograde
cerebral perfusion techniques.



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\textbf{Table 1:} Antegrade vs, retrograde cerebral perfusion strategies
mortality and stroke morbidity outcomes.\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\textbf{Study} & \textbf{N=} & \textbf{Mortality} & \textbf{Mortality} &
\textbf{Stroke} & \textbf{Stroke} & \textbf{Emergent cases} &
\textbf{Emergent cases}\tabularnewline
& & \emph{ACP} & \emph{RCP} & \emph{ACP} & \emph{RCP} & \emph{ACP} &
\emph{RCP}\tabularnewline
Abdelgawad A, et al 2017 \textsuperscript{23} & 43 & 3 (16.7\%) & 4
(16\%) & 1 (5.6\%) & 2 (8\%) & 6 (33.3\%) & 7 (28\%)\tabularnewline
Apaydin AZ, et al. 2009 \textsuperscript{36} & 239 & N/A & N/A & 2/13
(10\%) & 0 (0\%) & N/A & N/A\tabularnewline
Apostolakis E, et. al 2008 \textsuperscript{24} & 48 & 3/23 (13\%) &
4/25 (16\%) & 1/23 (4.3\%) & 1/25 (4\%) & N/A & N/A\tabularnewline
Ganapathi AM, et al 2014 \textsuperscript{14} & 440 & 3 (3.8\%) & 2
(2.5\%) & 2 (2.5\%) & 1 (1.3\%) & 11 (13.8\%) & 9
(11.3\%)\tabularnewline
Ghoreishi M, et al. 2019 \textsuperscript{27} & 7353 & N/A & N/A & 434
(46\%) & 184 (20\%) & N/A & N/A\tabularnewline
Itagaki S, et al. 2019 \textsuperscript{28} & 7830 & 207 (6.1\%) & 83
(4.4\%) & 179 (5.3\%) & 75 (4.0\%) & N/A & N/A\tabularnewline
Leshnower BG, 2019 \textsuperscript{26} & 20 & 0 & 0 & 1(9\%) & 1 (11\%)
& N/A & N/A\tabularnewline
Soliman S, et al. 2018 \textsuperscript{37} & 50 & 2 (8\%) & 3 (12\%) &
1 (4\%) & 1 (4\%) & N/A & N/A\tabularnewline
Stevens L, et al. 2009 \textsuperscript{38} & 195 & N/A & N/A & 5 (9\%)
& 0 (0\%) & N/A & N/A\tabularnewline
Sundt TM III, et al. 2008 \textsuperscript{39} & 347 & 2 (4.4\%) & 3
(9.4\%) & 2 (5.4\%) & 1 (7.1\%) & N/A & N/A\tabularnewline
Sugiura T, et al. 2012 \textsuperscript{40} & 203 & 2 (2.1\%) & 7
(6.4\%) & 11 (12\%) & 10 (9.2\%) & 94 (100\%) & 109
(100\%)\tabularnewline
Tokuda Y, et al. 2014 \textsuperscript{29} & 4128 & N/A & N/A & 311
(11.2\%) & 132 (9.7\%) & N/A & N/A\tabularnewline
Usui A, et al. 2012 \textsuperscript{41} & 2792 & 3.5\% & 2.6\% & 6.8\%
& 3.1\% & N/A & N/A\tabularnewline
Wiedemann D, et al. 2013 \textsuperscript{25} & 329 & 12 (13\%) & 20
(16\%) & 11 (12\%) & 15 (12\%) & N/A & N/A\tabularnewline
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion. &
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion. &
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion. &
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion. &
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion. &
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion. &
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion. &
ACP: antegrade cerebral perfusion; RCP: retrograde cerebral
perfusion.\tabularnewline
\bottomrule
\end{longtable}



\textbf{Figure legends}

\textbf{Figure 1:} Estimated safe duration of DHCA (HCA). From Yan et al
(Permitted third party reuse by the CC BY-NC-ND 4.0
license).\textbf{Figure 2:} Retrograde cerebral perfusion via SVC
cannulation, with venous drainage through the bicaval cannula during the
cooling phase. From Gravlee: Cardiopulmonary Bypass,
2\textsuperscript{nd} Ed. Wolters Kluwer, 2000.\textbf{Figure 3:}
Retrograde cerebral perfusion in a minimally invasive approach setting:
(A) Right lateral mini-thoracotomy incision entering the 4th intercostal
space. Patient's arm is always positioned over the head; (B) Surgical
field exposure with the SVC cannula in place and a completed hemiarch
anastomosis.\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-3A/Figure-3A}

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