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\begin{document}

\title{Continuous Cerebral and Myocardial Selective Perfusion in Neonatal
Aortic Arch Surgery}



\author[1]{Pierre Maminirina}%
\author[1]{Carine Pavy}%
\author[1]{Pierre Bourgoin}%
\author[1]{Olivier Baron}%
\affil[1]{University Hospital Centre Nantes}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\selectlanguage{english}
\begin{abstract}
BACKGROUND: To assess the feasibility and outcome of Continuous Cerebral
and Myocardial Selective Perfusion (CCMSP) during aortic arch surgery in
neonates. METHODS: This retrospective single-center study was conducted
between 2008 and 2019 in neonates undergoing aortic arch surgery,
accompanied or not by cardiac malformation repair. CCMSP at moderate
hypothermic of 28\selectlanguage{ngerman}°C was achieved using selective brachiocephalic artery
and ascending aorta cannulation. Target rates of cerebral and myocardial
perfusion were 25-35 mL/kg/min and 150/m2/min. Cardiopulmonary bypass
(CPB) variables and clinical outcomes were analyzed. RESULTS: Overall,
69 neonates underwent either isolated aortic arch repair (n=31) or
aortic arch repair with ventricular septal defect (VSD) closure (n=38).
The mean age and weight were 9.79±7.1 days and 3.17±0.4Kg, respectively.
Mean CPB and aortic clamping times were 133.5±47.0 and 25.2±5.3 min for
isolated aortic arch repair, and 158.4±47.9 and 75.4±30.5 min for
aortoplasty accompanied by VSD closure. Mean CCMSP time was 51.6±21.5
min with cerebral rate of 32.6±10.0mL/Kg/min. Two major complications
arose: stroke (n=1; 1.44\%) and transient renal failure requiring
dialysis (n=2; 2.89\%). Neither myocardial nor visceral ischemia
occurred. In-hospital mortality was 1/69 (1.44\%). CONCLUSIONS: CCMSP is
a safe and reproducible strategy for cerebral, myocardial and visceral
protection in neonatal aortic arch repair, with or without VSD closure,
resulting in low complication and mortality.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{INTRODUCTION}

Aortic arch surgery presents a challenge in neonates in terms of organ
protection. Deep hypothermic circulatory arrest (DHCA) has so far been
the most common adjunctive support technique. While this technique
protects vital organs due to hypothermia, it has the added technical
advantage of removing blood from the operative field (1). Though DHCA
provides time-limited protection, it is not devoid of damaging effects
(2). Though still a mainstay in congenital heart surgery, DHCA is
associated with poor neurodevelopmental outcome (3). Alternative
perfusion techniques have, therefore, been developed, such as antegrade
cerebral perfusion (ACP) combined with moderate hypothermic circulatory
arrest (MHCA) of the lower part of the body (4). This study sought to
evaluate the feasibility and efficacy of combined continuous cerebral
and myocardial selective perfusion strategy (CCMSP) as applied in our
center.

\textbf{METHODS}

\textbf{Patient population}

Between 2008 and 2019, 69 consecutive neonates underwent aortic arch
reconstruction, with or without intracardiac repair, in our center. All
presented with: coarctation of the aorta (CoA) with ventricular septal
defect (VSD), severe hypoplastic aortic arch (HAA) with or without VSD,
interrupted aortic arch (IAA). Their medical charts and surgical reports
were retrospectively analyzed. All neonates were undergoing their first
operation. All complex congenital malformation (Hypoplastic left heart
syndrome, Common arterial trunk\ldots{}) and surgical re-interventions
were excluded from analysis. Table 1 summarizes population
characteristics and lesion distribution.

\textbf{Surgical technique}

Following median sternotomy and thymus removal, an autologous
pericardial patch was harvested and fixed in glutaraldehyde. Figure 1
summarizes surgical technique applied in our center. The brachiocephalic
artery (BCA) was then cannulated using a Gore-Tex tube, and accomplished
bicaval venous cannulation. On initiating cardiopulmonary bypass (CPB),
core cooling was commenced. We tightened the clamps on the pulmonary
arteries to maximize body perfusion via the ductus arteriosus, while
continuing the preparatory dissection as necessary. When the rectal
temperature reached 28\selectlanguage{ngerman}°C, circulatory arrest in the lower part of the
body was begun by clamping the BCA at its origin. The CPB flow rate was
lowered to 25--35mL/Kg/min to ensure continuous ACP via the BCA. We
clamped the left subclavian artery and left common carotid artery to
optimize intracerebral perfusion pressure. At that point, our target was
a right radial artery blood pressure of \textgreater{}50mmHg, and a
bilateral near-infrared spectroscopy value of \textgreater{}50\%.
Anesthesia was induced using an intravenous midazolam injection, with
electrolyte and acid-base balances managed using the alpha-stat
approach. We first clamped the descending aorta followed by the
ascending aorta. At that point, we perfused the coronary arteries with
blood at 32°C with a rate of 150ml/m2/min. We divided the ascending
aorta just prior to the BCA's origin, then ligated and divided the
ductus arteriosus, resecting as much ductal tissue as possible. The
hypoplastic aortic arch was longitudinally opened, and all four ends
exposed. Next, we enlarged the arch using the autologous pericardial
patch as an aortic tube according to z-score normal size. Then, we
performed end-to-end anastomosis on the descending aorta to restore the
continuity of the arch and descending aorta. The heart had thus far been
kept beating during the procedure. At this point, we induced
cardioplegia using a potassium-enriched solution to arrest the heart.
Next, we removed the clamp from the ascending aorta, re-established the
continuity of the ascending aorta to aortic arch and respecting its good
concavity shape. We then provoked retrograde purging of the aorta and we
gradually increased the CPB flow rate, removing the clamp from the BCA.
The CPB was then resumed, with the flow rate calculated to ensure
systemic patient perfusion. Before proceeding to rewarming, we carefully
checked for any hemorrhaging. Next, we performed a possible additional
repair during the rewarming period, such as VSD closure. We weaned the
CPB when the rectal temperature reached 36.5°C. We administered
hemostatic products to ensure good hemostasis. The sternum was initially
left open if necessary. Nowadays, sternum is usually closed immediately

\textbf{RESULTS}

\textbf{Duration of CPB and aortic clamping}

Table 2 illustrates the duration of CPB and aortic clamping according to
surgical repair procedure. The mean durations of CPB and aortic clamping
upon aortoplasty were 133.5±47.0 and 25.2±5.3 minutes. Longer durations
were observed in case of VSD closure. For these, the mean durations of
CPB and aortic clamping were 158.4±47.9 and 75.4±30.5 minutes
respectively.

\textbf{Cerebral and myocardial perfusion}

Table 3 provides the parameters recorded during CCMSP. The mean duration
of CCMSP was 51.6±21.5 minutes (median: 52). The mean cerebral perfusion
flow rate was 32.6±10.0mL/Kg/min. The mean cooling time was 22.5±1
minutes with a median of 21 minutes whereas the mean rewarming time was
42.6±16.3 minutes with a median of 40 minutes. Arterial perfusion and
venous return temperatures were practically identical: 26.4 vs. 26.9°C.
The rate of myocardial perfusion was constant at 150 ml/m2/min according
to our protocol.

\textbf{Major complications}

\textbf{Neurological complications}

One case of stroke (1.44\%) occurred in a male neonate aged 30 days and
weighing 3Kg, with severe HAA and VSD, admitted to our pediatric intense
care unit in a state of cardiogenic shock. His hemodynamics improved
upon inotropic medication, and surgery was performed 24 hours
post-admission, consisting of complete reconstructive aortoplasty and
VSD closure. CPB lasted 181 minutes, aortic clamping 90 minutes, and
CCMSP of 55 minutes. After weaning from CPB failed, the neonate was
placed on central extracorporeal membrane oxygenation (ECMO), and then
withdrawn from ECMO after 7 days. Thereafter, the infant displayed
marked global developmental delay, brain imaging revealing ischemic and
hemorrhagic lesions in the frontal and occipital regions.

\textbf{Renal complications}

Two (2.89\%) neonates developed transient renal failure requiring
dialysis with patients' characteristics listed in Table 4. They weighed
less than 3kg underwent total reconstruction for HAA and concomitant VSD
with CPB for over 150 minutes. Durations of CCMSP were 42 and 46
minutes.

No myocardial or visceral ischemia complications were observed in our
study.

\textbf{In-hospital mortality}

The mortality rates were 1.44\% (1/69). The cause of death was a septic
shock Escherichia coli-related.

\textbf{DISCUSSION}

\textbf{Surgical treatment indication and approach}

All surgical practitioners in our center followed the same protocol for
aortic arch surgery. We have a firm preference for performing one-step
complete arch reconstruction in neonates with CoA with VSD. Within the
Society of Thoracic Surgeons (STS) Congenital Heart Surgery database,
Ross and colleagues (5) identified 840 patients treated for CoA with
VSD, 211 (25\%) of whom underwent VSD closure and 89 (11\%) pulmonary
artery banding, whereas 540 (64\%) did not undergo VSD closure. In this
study, in-hospital mortality proved low, without significant
between-strategy differences. In our center, HAA or CoA without VSD are
treated differently, depending on the lesion extent. Arch enlargement
plasty via median sternotomy is our preferred approach for severe
proximal HAA cases. This also applies to any aortic Segment I hypoplasia
with a Z-score \textless{}-3 and diameter inferior to body weight (Kg)
+1mm. Similarly, we prefer this approach for managing supra-aortic
artery abnormalities like bovine arch. Complete reconstruction via
median sternotomy and CPB enables good arch reconstruction without
requiring aortic clamping at the BCA's origin. Of note, median
sternotomy enables us to simultaneously close any associated atrial
septal defect, thereby improving left ventricular preload. Optimizing
this preload further improves left ventricular development, and that of
the aorta downstream, potentially reducing reoperation rates (6). The
Sakurai and colleagues' study involved 288 patients treated for CoA and
HAA without VSD over two decades. Their analysis revealed a trend
towards a higher number of sternotomies during the second decade (36\%
vs. 6\%), along with a significantly low reoperation rate (5\% vs. 16\%,
p=0.02) (7).Complete reconstruction via lateral thoracotomy, using the
extended Crafoord technique (8) without CPB, is the approach we prefer
in case of isolated isthmic CoA, either small in size or extending as
far as Segment II .Over a 10-year period (2008--2019), we performed 180
lateral thoracotomies versus 31 median sternotomies, all age groups
taken together.

\textbf{Surgical procedure and perfusion technique}

Generally, we select the perfusion technique depending on the patient's
age and aortic arch repair complexity. CCMSP at 28°C is our preferred
technique for all extensive aortic arch reconstruction in neonates. DHCA
is rarely performed, rather reserved for more complex repairs.
Whole-body perfusion at normothermia without circulatory arrest,
indicated for older children, is achieved by perfusing the brain via the
BCA and the body via femoral artery cannulation. According to the
literature, the perfusion techniques in pediatric aortic arch surgery
vary widely and the debate is never ending, with no established
consensus as of yet. MHCA with ACP is likely to provide improved brain
protection with fewer neurological complications (2)(3)(9) though
several authors were unable to clearly demonstrate ACP's superiority
over DHCA in terms of neurocognitive complications. In a randomized
controlled trial comparing DHCA versus ACP, Algra and colleagues did not
detect any between-group difference in new neurological injuries on
immediate post-operative MRI or in neurocognitive or motor outcomes at
24 months (10). Using the STS database with 4,523 American patients,
Meyer and colleagues reported ACP to have increasingly become the new
trend, used 43\% of times versus 32\% for DHCA (11). Approximately 16\%
of centers employ a mixed approach comprising both a complete
circulatory arrest and an ACP during the same procedure.

\textbf{Target temperature and flow rate}

In our cohort, we opted for a rectal target temperature of 28°C. This
target temperature was perfectly aligned with the CPB temperatures
recorded during circulatory arrest of the lower part of the body,
attesting to a relatively stable hypothermia. Mean venous return and
arterial perfusion temperatures were 26.9°C and 26.4°C, with medians of
27°C and 26.5°C during CCMSP. According to our calculations, an ACP flow
rate of 25--35mL/Kg/min was adequate, whereas the mean flow rate
recorded was 32.6±10.0mL/kg/min, with a median of 30.5mL/Kg/min. A
temperature of 28°C and ACP flow rate of 25--35mL/Kg/min had been fixed
as objectives, based on our center's experience in adult aortic surgery
and several studies involving hypothermic pump flow rates and blood gas
management published in the literature (12)(13)(14). Our target
parameters for cerebral and visceral protection are: right radial artery
blood pressure \textgreater{}50mmHg, bilateral near infrared
spectroscopy (NIRS) values \textgreater{}50\%, transcranial Doppler flow
velocity \textgreater{}15-20cm/s, and mixed venous oxygen saturation
\textgreater{}60\%. Body temperatures and cerebral perfusion rates
during circulatory arrest are a matter of endless debate. Several
authors have performed ACP during normothermia, aiming to achieve better
protection by staying as close as possible to the normal human
physiological state. To maintain normothermia, they are now
experimenting with splanchnic perfusion to prevent renal and gut
exposure to circulatory arrest. These authors have reported satisfactory
results in terms of visceral and neurological function (15). Notably,
Fraser and colleague recommended a higher ACP flow rate at
50--80mL/Kg/min (14). Nevertheless, our strategy of applying CCMSP at
28°C with flow rate of 25--35mL/Kg/min has so far yielded suitable
results, which will be discussed in more detail later.

\textbf{Myocardial protection}

In all cases, we performed continuous blood coronary perfusion, in an
effort to maintain the heart beating during aortic arch repair. To
maximize myocardial protection, we shortened the duration of cardiac
arrest as much as possible. We reserve cardiac arrest to perform our
aorta proximal anastomosis in order to achieve a good, extensive,
arch-shaped augmentation. The duration of cardiac arrest can be extended
for any additional repair procedure. In their study, Lim and colleagues
compared two perfusion groups involving 97 neonates operated on for CoA
and HAA with VSD, IAA with VSD or aortic abnormality associated with
complex cardiac malformations (16). In all cases, simultaneous cerebral
and myocardial perfusion displayed superiority in terms of vasopressin
use and extubation versus cerebral perfusion alone. In the most complex
cases, simultaneous cerebral and myocardial perfusion was additionally
shown to be superior in terms of vasoactive inotrope use, secondary
sternal closure, removal of chest tubes, pleural effusion, and ICU and
hospital stay duration. In our center, we apply a patch of autologous
pericardium as augmentation material, preferring this approach to the
direct resection/anastomosis technique. This patch technique enables us
to achieve a good post-repair arch shape. While this procedure may
slightly prolong the reparation in comparison with direct
resection/anastomosis, we favor the anatomical outcome, along with good
visceral and cerebral protection, over simple circulatory arrest
duration. Our mean CCMSP duration of 51.6±21.5 minutes is roughly in
line with that of the literature. In the aforementioned Meyer report
using the STS database, the mean circulatory arrest duration with
cerebral perfusion was 45.0 (30.0--63.0) minutes (12).

\textbf{Major complications and mortality}

Our study generated very promising results concerning mortality (1.44\%)
and major complications, with only one case (1.44\%) of neurological
injury and two cases (2.89\%) of transient renal failure requiring
dialysis. No myocardial or visceral ischemic injuries were observed.
Currently, aortic arch repair with or without VSD repair using median
sternotomy and CPB is a well-mastered technique. Despite long CPB or
circulatory arrest times in several cases, CCMSP at moderate hypothermic
circulation was able to ensure good organ protection. Despite of the
circulatory arrest of the lower part of the body, organ perfusion are
ensured by multiple vascular communication through the selective
cerebral perfusion. That's why we clamp the descending aorta during the
aortic arch reparation to avoid back flow. On note is that we do not
perform systematic brain imaging after arch surgery, reserving imaging
for children with clinical neurological disorders. Overall, our clinical
results are very satisfactory. Concerning cerebral protection, Rüffer
and colleagues demonstrated symmetrical perfusion of both cerebral
hemispheres during ACP (17), while Algra and colleagues clearly
illustrated how continuous cerebral perfusion during neonatal aortic
arch surgery caused decreased circulatory arrest-induced renal and
visceral injury (18). Comparing the two perfusion techniques performed
at 18°C, the latter study reported that ACP was superior to DHCA in
terms of abdominal perfusion, as confirmed by near-infrared spectroscopy
data, postoperative inferior vena cava lactate levels, and renal and
gastrointestinal injury biomarkers.

\textbf{Limitations and strengths}

This study's limitations lay in its retrospective nature and patient
population's heterogeneity, with study data solely derived from
patients' hospital charts. We also lacked laboratory data or imaging
reports enabling us to identify subclinical abnormalities. Moreover, the
neurological assessment was solely based on clinical findings
followed-up by imaging, without any established imaging protocol
applied. The next necessary step is now a prospective study using
exhaustive data collection according to a pre-established protocol to
fully assess this surgery and perfusion technique.

\textbf{CONCLUSION}

Aortic arch surgery during the neonatal period still poses a challenge
in terms of feasibility and outcome. Choosing the appropriate perfusion
technique is vital for ensuring better long-term outcomes. There is no
consensus yet as to either the perfusion type or the temperature and
flow rates of cerebral perfusion. Dual selective cerebral and coronary
continuous perfusion at moderate hypothermic circulatory appears
feasible, reliable, and reproducible, while ensuring maximal cerebral
and visceral protection, without exposure to ischemic complications.

\textbf{REFERENCES}

1. Castaneda AR, Mayer JE Jr, Jonas RA, Lock JE, Wessel DL, Hickey PR.
The neonate with critical congenital heart disease: repair--a surgical
challenge. J Thorac Cardiovasc Surg. 1989;98:869-875.

2. Newburger JW, Jonas RA, Wernovsky G, Wypij D, Hickey PR, Kuban KC et
al. A comparison of the perioperative neurologic effects of hypothermic
circulatory arrest versus low-flow cardiopulmonary bypass in infant
heart surgery. N Engl J Med. 1993;329:1057-1064.

3. Oates RK, Simpson JM, Turnbull JAB, Cartmill TB. The relationship
between intelligence and duration of circulatory arrest with deep
hypothermia. J Thorac Cardiovasc Surg. 1995;110:786-792.

4. Pigula FA, Siewers RD, Nemoto EM. Regional perfusion of the brain
during neonatal aortic arch reconstruction. J Thorac Cardiovasc Surg
1999;117:1023--1024.

5. Ross M. Ungerleider, Sara K. Pasquali, Karl F. Welke et al.
Contemporary patterns of surgery and outcomes for aortic coarctation: An
analysis of the Society of Thoracic Surgeons Congenital Heart Surgery
Database. J Thorac Cardiovasc Surg. 2013; 145: 150-157.

6. Rüffer A, Bechtold C, Purbojo A, Toka O, Glöckler M, Dittrich etal.
Aortic arch obstruction neonates with biventricular physiology:
left-open compared to closed inter-atrial communication during primary
repair--a retrospective study. J Cardiothorac Surg. 2015;17;10:53.

7. Sakurai T, Stickley J, Stümper O, Khan N, Jones TJ, Barron DJ et al.
Repair of isolated aortic coarctation over two decades: impact of
surgical approach and associated arch hypoplasia. Interact Cardiovasc
Thorac Surg. 2012;15: 865-870.

8. Crafoord C, Nylin G. Congenital coarctation of the aorta and its
surgical treatment. J Thorac Surg. 1945; 14: 347-361.

9. Andropoulos DB, Easley RB, Brady K, McKenzie ED, Heinle JS, Dickerson
HA, et al. Neurodevelopmental outcomes after regional cerebral perfusion
with neuromonitoring for neonatal aortic arch reconstruction. Ann Thorac
Surg. 2013;95: 648-654.

10. Algra SO, Jansen NJ, van der Tweel I, Schouten AN, Groenendaal F,
Toet M et al. Neurological injury after neonatal cardiac surgery: a
randomized, controlled trial of 2 perfusion techniques. Circulation
2014;129:224-33.

11. Meyer DB, Jacobs JP, Hill K, Wallace AS, Bateson B, Jacobs ML.
Variation in Perfusion Strategies for Neonatal and Infant Aortic Arch
Repair: Contemporary Practice in the STS Congenital Heart Surgery
Database.World J Pediatr Congenit Heart Surg. 2016;7:638-644.

12. Sasaki T, Tsuda S, Riemer RK, Ramamoorthy C, Reddy VM, Hanley FL.
Optimal flow rate for antegrade cerebral perfusion. J Thorac Cardiovasc
Surg 2010; 139: 530-535.

13. Oppido G, Pace Napoleone C, Turci S, Davies B, Frascaroli G,
Martin-Suarez S et al. Moderately hypothermic cardiopulmonary bypass and
low-flow antegrade selective cerebral perfusion for neonatal aortic arch
surgery. Ann Thorac Surg. 2006; 82 :2233-2239.

14. Fraser CD Jr, Andropoulos DB. Principles of antegrade cerebral
perfusion during arch reconstruction in newborns/infants. Semin Thorac
Cardiovasc Surg Pediatr Card Surg Annu. 2008:61-68.

15. Raees MA, Morgan CD, Pinto VL, Westrick AC, Shannon CN, Christian KG
et al. Neonatal Aortic Arch Reconstruction With Direct Splanchnic
Perfusion Avoids Deep Hypothermia. Ann Thorac Surg. 2017;104:2054-2063

16. Lim HG, Kim WH, Park CS, Chung ES, Lee CH, Lee JR et al. Usefulness
of Regional Cerebral Perfusion Combined With Coronary Perfusion During
One-Stage Total Repair of Aortic Arch Anomaly. Ann Thorac Surg.
2010;90:50 --57.

17. Rüffer A, Tischer P, Münch F, Purbojo A, Toka O, Rascher W et al.
Comparable Cerebral Blood Flow in Both Hemispheres During Regional
Cerebral Perfusion in Infant Aortic Arch Surgery. Ann Thorac Surg.
2017;103:178-185.

18. Algra SO, Schouten AN, van Oeveren W, van der Tweel I, Schoof PH,
Jansen N et al. Low-flow antegrade cerebral perfusion attenuates early
renal and intestinal injury during neonatalaortic arch reconstruction. J
Thorac Cardiovasc Surg. 2012;144:1323-8, 1328

\textbf{Figure and Table legends}

\textbf{Table 1:} Patient demographics and diagnosis. \emph{VSD:
Ventricular septal defect; SD: standard deviation}

\textbf{Figure 1} : Surgical technique.1)BCA cannulation. 2) Circulatory
arrest at 28°C; antegrade cerebral perfusion: 25-35mL/Kg/min; clamping
of BCA, left common carotid artery, left subclavian artery. 3) Clamping
of ascending aorta and descending aorta. 4) Aortoplasty using autologous
pericardial patch. 5) Blood coronary perfusion without cardioplegia. 6)
Proximal anastomosis; open aorta; cardiac arrest. 7) Systemic flow rate
reestablished. 8) VSD closure. \emph{Note: The red arrows indicate the
blood flow direction. BCA:brachiocephalic artery; VSD: ventricular
septal defect.}

\textbf{Table 2} : CPB and aortic clamping according to repair
procedure.\emph{CPB: Cardiopulmonary bypass, VSD: Ventricular septal
defect}

\textbf{Table 3} : Parameters recorded during CCMSP

\textbf{Table 4} : Characteristics of neonates with kidney complications
requiring dialysis. \emph{HAA: Hypoplastic aortic arch, VSD: Ventricular
septal defect, CPB: Cardiopulmonary bypass}

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