ARTICLE IN PRESS

Journal of Cardiothoracic and Vascular Anesthesia 000 (2023) 112

Contents lists available at ScienceDirect

Journal of Cardiothoracic and Vascular Anesthesia

journal homepage: www.jcvaonline.com

Expert Review
Hypothermic Circulatory Arrest in Adult Aortic Arch
Surgery: A Review of Hypothermic Circulatory Arrest
and its Anesthetic Implications
Samit Ghia, MD*, Andre Savadjian, MDy, DaWi Shin, BS *,
z *,1
Gabriele Diluozzo, MD , Menachem M. Weiner, MD ,
Himani V. Bhatt, DO, MPA, FASE, FASA*
*
Department of Anesthesiology, Critical Care and Perioperative Medicine, Icahn School of Medicine at
Mount Sinai, New York, NY
y
Department of Anesthesiology and Critical Care, Duke University School of Medicine, Durham, NC
z
Department of Cardiovascular Surgery, Yale School of Medicine, Bridgeport, CT

Diseases affecting the aortic arch often require surgical intervention. Hypothermic circulatory arrest (HCA) enables a safe approach during open
aortic arch surgeries. Additionally, HCA provides neuroprotection by reducing cerebral metabolism and oxygen requirements. However, HCA
comes with significant risks (eg, neurologic dysfunction, stroke, and coagulopathy), and the cardiac anesthesiologist must completely understand
the surgical techniques, possible complications, and management strategies.
Ó 2023 Elsevier Inc. All rights reserved.

Key Words: deep hypothermic circulatory arrest; aortic surgery

THE AORTIC ARCH has 3 major branches that perfuse the History of Therapeutic Hypothermia in Medicine
upper extremities and brain. Thoracic aortic aneurysms and
acute aortic syndromes affecting the arch often require surgical The first documented use of therapeutic hypothermia was in
intervention.1 To perform this complex endeavor, cessation of The Edwin Smith Papyrus, which dates back to 3500 B.C. One
flow across the arch is necessary to permit surgical visualiza- case from the Papyrus implemented a cool media for a chest
tion. Although external shunts have been implemented in the blister.4 Around 3,000 years later, Hippocrates used snow to
past, circulatory arrest is the optimal approach and is more induce hypothermia and aid healing.5 Originally, hypothermia
commonly used for exposure.2 However, circulatory arrest for neuroprotection was done by cold water immersion.6 Bige-
results in organ ischemia, fraught with the risk of organ injury, low was the first to use hypothermia in cardiac surgery during
particularly in the brain. To protect against ischemia and mini- canine experimentation at temperatures of 20˚C.5 This
mize cellular damage, hypothermia is instituted commonly to research jump-started Lewis to perform his first human cardiac
reduce metabolism and oxygen requirements.3 The objective surgery to close an atrial septal defect with the assistance of
of this article is to review hypothermic circulatory arrest hypothermia in 1952.7
(HCA) in adult aortic arch reconstruction and the perioperative More than a decade later, Barnard and Schrire first used pro-
concerns of cardiac anesthesiologists. found HCA and cardiopulmonary bypass (CPB) simulta-
neously to repair ascending aortic and aortic arch aneurysms
1
in 2 patients.8 The modern use of HCA began in 1975 when
Address correspondence to Menachem M. Weiner, MD, Department of Griepp used surface cooling with CPB to resect aortic arch
Anesthesiology, Box 1010, The Mount Sinai Medical Center, One Gustave L.
Levy Place, New York, NY 10029.
aneurysms in 4 patients. His technique began with surface
E-mail address: [email protected] (M.M. Weiner). cooling to 30 C with a cooling blanket, and after placement on

https://doi.org/10.1053/j.jvca.2023.08.139
1053-0770/Ó 2023 Elsevier Inc. All rights reserved.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
2 S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112

CPB via the right atrium and left femoral artery, surface and recommend that a diameter of 4 and 4.5 cm for most patients
internal cooling brought the core temperature to 12 C to 15 C. should be defined as dilated and aneurysmal, respectively.14
Once the target hypothermia was achieved, circulatory arrest Aortic aneurysms can progress into dissections and/or rup-
commenced.9 tures.14 For this reason, surgical replacement will be indicated
when aortic diameter thresholds are met, which vary based on
Role of Hypothermic Circulatory Arrest factors including disease mechanism, genetics, family history,
and aneurysm progression. Table 1 summarizes class 1 recom-
Flow cessation during aortic arch surgery allows for ade- mendations for surgical intervention of disease involving the
quate surgical visualization and exposure, and implementation aortic root, ascending aorta, and/or aortic arch per the
of hypothermia limits ischemic sequelae of circulatory arrest. 2022 ACC/AHA Guideline for the Diagnosis and Management
Acutely, every drop of 1˚C in body temperature reduces the of Aortic Disease.14
cerebral metabolic rate of oxygen (CMRO2) by 6% to 7%.10,11
Cerebral metabolism, linearly correlated to temperature, is
directly proportional to glucose and adenosine triphosphate Acute Aortic Syndromes
consumption. As metabolism decreases with hypothermia, so
will the usage of glucose and phosphate stores. In addition, Acute aortic syndromes include aortic dissection, aortic
cooling reduces the excitotoxicity normally seen with cerebral intramural hematoma, and penetrating atherosclerotic ulcer.1
injury by limiting the release of excitatory mediators such as Clouse et al. analyzed a database of patients from Olmsted
glutamate. In the subacute phase, which ranges from hours to County, Minnesota, over a 15-year period, and found acute
days, hypothermia suppresses proinflammatory and proapop- aortic dissections an incidence of approximately 3.5 cases per
totic mediators. Hypothermia also limits injury from ischemia- 100,000 person-years.15 Intramural hematoma and penetrating
reperfusion by attenuating the release of reactive oxygen spe- atherosclerotic ulcer have lower annual incidences than aortic
cies. Lastly, cooling inhibits metalloproteinases from degrad- dissections at 2.1 and 1.2 per 100,000 person-years,
ing the extracellular matrix, which results in blood-brain respectively.16
barrier preservation.11 Aortic dissections are intimal tears that allow blood to enter
the media. The common causes of intimal tears include aortic
wall inflammation, trauma, degeneration of the aortic media,
Indications For Aortic Arch Reconstruction
and cystic medial necrosis.15 Intramural hematoma is distinct
Thoracic Aortic Aneurysms from an aortic dissection because hemorrhage into the aortic
wall occurs without an intimal tear. One-third of intramural
Aortic aneurysms develop in 3% to 4% of patients 65 years hematoma cases can progress into an aortic dissection or rup-
old and above. A thoracic aortic aneurysm occurs less fre- ture. Intramural hematoma is associated with similar risk fac-
quently than an abdominal aortic aneurysm, with an annual tors to those of an aortic dissection, including chronic
incidence of 6 cases per 100,000 person-years.12,13 hypertension, congenital cardiac anomalies, bicuspid aortic
The conventional definition of an arterial aneurysm is a dila- valve, connective tissue disorders, aortitis, decelerating or iat-
tion >50% of the normal diameter. However, per the 2022 rogenic trauma, pregnancy, and cocaine abuse.17 Penetrating
American College of Cardiology/American Heart Association atherosclerotic ulcers, which are found predominantly in the
(ACC/AHA) Guideline for the Diagnosis and Management of descending aorta, are due to the development of atherosclerotic
Aortic Disease, many dilated aortic roots and ascending aortas plaque that ulcerates and penetrates the elastic lamina of the
requiring intervention would be missed. The guidelines aortic wall, and is associated with atherosclerotic risk

Table 1
Class 1 Recommendations for Surgical Intervention of the Aortic Root, Ascending Aorta, and/or Aortic Arch per 2022 American College of Cardiology/American
Heart Association Guideline for the Diagnosis and Management of Aortic Disease14

Disease Threshold for Surgical Intervention

Nonsyndromic Heritable Thoracic Aortic Disease: asymptomatic, 5.0 cm diameter

no genetic cause, no family history
Marfan syndrome 5.0 cm diameter
LoeysDietz syndrome Based on genetic variant, aortic size/progression, age, sex, and family history
Bicuspid aortic valve 5.5 cm diameter
Sporadic aneurysms of aortic root and ascending aorta Attributable symptoms
Sporadic aneurysms of aortic root and ascending aorta: asymptomatic 5.5 cm diameter or growth rate 0.3 cm/year over 2 y or 0.5 cm in 1 y
Aortic arch aneurysm Attributable symptoms and low or intermediate operative risk
Acute type-A aortic dissection No additional requirements, proceed to intervention
Acute type-A intramural hematoma No additional requirements, proceed to intervention
Penetrating atherosclerotic ulcer Presence of aortic rupture, intramural hematoma, or symptomatic/pain
consistent with radiologic findings

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112 3

factors.18 Disease isolated to the aortic arch is rare and more blood. They found that rewarming slowly with a gradient of
often propagates to either the ascending or descending aorta.19 2 C had better neurocognitive function 6 weeks after surgery
and lower postoperative hyperthermia.23
Surgical Techniques for HCA
Optimal Temperature Target
The arterial cannula is often placed in the innominate or
axillary artery. Other options include central cannulation or Although the benefit of hypothermia is universally accepted,
cannulation of the femoral artery. If the femoral artery is there is no consensus on the ideal temperature for HCA. Cere-
accessed, the Seldinger technique with wire visualization via bral metabolism increases linearly when temperature rises,
transesophageal echocardiography (TEE) can help confirm which causes greater consumption of oxygen, adenosine tri-
true lumen cannulation. Subsequently, the right atrium is can- phosphate, and glucose, leading to more ischemia.11 Con-
nulated for venous drainage, the coronary sinus is cannulated versely, temperature drops increase the risk of coagulopathy,
for retrograde cardioplegia, and the left ventricle is vented to hyperglycemia, acidemia, and total CPB time. Decades of ani-
prevent distention. After CPB onset, the patient is cooled to a mal research have aimed to discover the optimal temperature
predetermined temperature via a heat exchanger.4 Temperature and how long it can be tolerated.24
gradients between the venous inflow and arterial outlet during Building upon animal research, McCullough et al. investi-
CPB cooling should not exceed 10˚C to avoid generating gas- gated the quantification of metabolic suppression during HCA.
eous emboli.20 Once the desired temperature is reached, CPB The CMRO2 and differences in cerebral arterial and venous
flow is stopped, marking the onset of HCA. Generally, once oxygen were estimated using the CBF. Plotting CMRO2 versus
the distal aortic graft is anastomosed, a cross-clamp is applied temperature extrapolated the temperature coefficient Q10,
to the graft, and CPB flow is reinstituted through the side arm which defines a ratio of CMRO2 at one temperature and
of the graft to the head and/or body while the proximal graft is another at a temperature 10 C. In their analysis of 37
anastomosed (Fig 1). Although there is no supporting evi- patients, assuming interrupted CBF can be permitted for 5
dence, most surgeons will resume CPB but delay rewarming to minutes at 37 C, derived calculations via the Q10 determined
reduce the risk of increasing intracranial pressure, presumably cooling to 15˚C was safe for approximately 30 minutes. Of the
secondary to the increased cerebral blood flow (CBF) associ- 37 patients, 5 received selective cerebral perfusion averaging
ated with rising temperature.3,10 After post-HCA hypothermic 37 minutes, 6 received retrograde flushing averaging 7
perfusion, rewarming must proceed gradually, with the differ- minutes, and 13 received retrograde cerebral perfusion (RCP)
ence between the venous inflow blood and the arterial outlet averaging 25 minutes.25
blood never exceeding 10 C. In contrast, the arterial outlet In 2013, an international panel of global experts proposed a
blood temperature is <30 C and not exceeding 4 C when the classification for temperature ranges of systemic HCA, which
temperature is >30 C.20-22 Grigore et al. studied more strin- is summarized in Table 2.26
gent gradients between temperatures of perfusate and systemic In patients cooled to 14.1˚C, at 20.1˚C, and 28˚C, elec-
troencephalogram (EEG) silence was not achieved in 14% to
22%, 75% to 98%, and 99% to 100%, respectively.27 McCul-
lough et al. studied the CMRO2 at various temperatures during
HCA, and found increases in CMRO2 of 5% and 8% between
10˚C and 15˚C and 15˚C and 20˚C, respectively. This increase
in metabolism is accelerated at higher temperatures. The
authors concluded that profound and deep hypothermia with
RCP may be safe, assuming circulatory arrest is <30 minutes,
but longer arrest time may require even lower temperatures.25
Although profound hypothermia confers a slight cerebral
physiologic advantage, the increased time to cool and rewarm
increases the risk of significant coagulopathy.3,28 As such,
many institutions have been moving toward moderate

Table 2
Classification of Temperature Ranges for Hypothermic Circulatory Arrest26

Category Temperature
Range (in  C)

Profound 14
Fig 1. The proximal anastomosis is sutured between the synthetic graft and Deep 14.1-20
ascending aorta proximal to the innominate artery takeoff. Inn, innominate Moderate 20.1-28
artery; LCCA, left common carotid artery; LSCA, left subclavian artery; Mild 28.1-34
RCCA, right common carotid artery.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
4 S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112

hypothermia with adjuvant perfusion strategies.29 Moderate oxygenator via cardiotomy suction in the open thoracic cavity.
hypothermia has lower rates of endothelial dysfunction, bypass Retrograde cerebral perfusion can be administered continu-
duration, coagulopathy, and renal dysfunction.30,31 ously, intermittently, and/or after HCA. Retrograde blood flow
is titrated to a pressure of 15-to-25 mmHg, which can be mea-
Adjuvant Therapy for Neuroprotection sured via a central venous catheter in the SVC or a jugular
bulb catheter. Monitoring cerebral perfusion adequacy during
Adjuvant perfusion strategies for cerebral protection include RCP can be done by near-infrared spectroscopy (NIRS) and/or
antegrade cerebral perfusion (ACP) and RCP. Both techniques transcranial Doppler (TCD).35
provide CBF during arrest, which theoretically can allow for Retrograde cerebral perfusion’s theoretical benefits include
prolonged periods of HCA. However, each technique has pros flushing the cerebral vasculature of waste products, embolic
and cons, and different institutions have had varying degrees debris, and air. Although RCP should provide cerebral perfu-
of success with their use.32 sion and cooling, global cerebral capillary perfusion may be
heterogeneous and insufficient.21 Coselli found that RCP use
Retrograde Cerebral Perfusion reduced in-hospital mortality from 17.2% to 3.9%, and the
incidence of permanent stroke from 6.4% to 2.6%.36 Safi eval-
During aortic arch surgery, Lemole introduced RCP in 1982 uated 1,193 patients who underwent ascending aorta and/or
by supplying cold oxygenated blood to the cerebral vascula- aortic arch surgery with HCA, and found no statistical signifi-
ture via the superior vena cava (SVC).33 In 1990, Ueda et al. cance in the stroke rate with (2.8%) or without RCP (4.2%).
were the first to describe the clinical application of continuous However, if the HCA exceeded 40 minutes, the stroke rate was
RCP with deep hypothermia for aortic surgery.34 significantly lower, with RCP at 1.7% compared with 30%
Retrograde cerebral perfusion is administered after the onset without.37 Beyond the potential benefit seen with the prior
of HCA. A cannula is inserted into the SVC and then snared studies, Lau found that adjuvant administration of RCP did not
(Fig 2). The arterial inflow cannula is occluded, and a connec- cause harm. In their propensity-matched retrospective study,
tion between the arterial return line and the SVC cannula is deep HCA with RCP did not increase the incidence of intrao-
opened. Perfused blood travels retrograde through the internal perative mortality, neurologic deficit, or major perioperative
jugular veins to cerebral tissue before entering the carotid complications.38
arteries into the arch. The blood is then returned to the However, some data have questioned whether the oxygen
delivery from RCP is sufficient for cerebral protection.35,39-42
Two investigations showed that jugular venous valves are a
major impediment to perfusate delivery throughout the
brain.43,44 Another investigation by Katz in 1999 showed only
minimal technetium 99m-labeled albumin circulating through
cerebral tissue when injected as part of RCP.45 Retrograde
cerebral perfusion usage has faded for a number of reasons.
This is primarily due to an increased level of comfort with
ACP (see next section) and studies showing the benefit of
ACP use. Furthermore, deep HCA alone provides sufficient
cerebral and visceral organ protection when limited to 30
minutes, which was the timeframe in most published RCP
cases. Therefore, it is inconclusive if supplementing RCP is
beneficial.41,42,45

Antegrade Cerebral Perfusion

Antegrade cerebral perfusion is another strategy of selective

cerebral perfusion to obviate neurologic sequelae during HCA.
During ACP, the right axillary or brachial artery commonly is
cannulated for arterial inflow. Other techniques include direct
cannulation of the subclavian artery or bilateral carotid arter-
ies.21 The axillary artery is more delicate than the aortic arch,
but an end-to-side graft anastomosis is preferred over cannula-
tion due to a lower complication rate. Axillary artery dissec-
tion and postoperative upper extremity ischemia occurred in
Fig 2. The retrograde cerebral perfusion cannula is placed into the superior 9% and 4.5% of the direct cannulation group, respectively, but
vena cava and snared. This will provide retrograde blood flow via the internal
jugular veins. CPB, cardiopulmonary bypass; LIJV, left internal jugular vein; neither complication occurred in the graft anastomosis
RCP, retrograde cerebral perfusion; RIJV, right internal jugular vein; SVC, cohort.46 Upon HCA onset, the innominate artery is clamped,
superior vena cava. and unilateral ACP is administered via the right axillary

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112 5

perfusion. With moderate hypothermia, ACP has safely

allowed for longer periods of HCA. Perreas compared 259
patients who had aortic arch surgery with either deep HCA
and RCP or moderate HCA and ACP in a propensity-matched
analysis. The study showed that the latter group had signifi-
cantly reduced postoperative neurologic complications (50% v
17.5%), 30-day mortality (22.5% v 7.5%), and midterm mor-
tality (40% v 15%).53,54 Research over the last decade has
focused more on moderate hypothermia, possibly improving
patient outcomes.
Deep HCA alone, when exceeding 45 minutes, is associated
with an increased incidence of permanent neurologic injury. In
shorter periods of arrest, HCA is safe and, therefore, used in
straightforward cases. Compared with RCP, ACP permits lon-
ger circulatory arrest but increases the risk of atherosclerotic
emboli. More reliable cerebral cooling and flow exists, but
manipulating potentially pathologic, atherosclerotic, or friable
vessels adds to an already high-risk surgery. Antegrade cere-
bral perfusion also introduces the possibility of graft kinking,
which can impair CBF. Both strategies have risks and benefits,
but ACP is preferred because it permits the use of moderate
hypothermia during HCA.21,55,56
Per the 2022 ACC/AHA Guidelines for Diagnosis and Man-
agement of Aortic Diseases, implementation of either ACP or
RCP is superior to HCA alone, and ACP leads to less long-
Fig 3. The antegrade cerebral perfusion cannula is placed via a sheath
attached to the right subclavian artery. It will provide antegrade cerebral blood
term mortality and neurologic dysfunction. Bilateral ACP may
flow via the right vertebral and right common carotid arteries. ACP, antegrade be superior in cases when HCA is >30 minutes but insignif-
cerebral perfusion; CPB, cardiopulmonary bypass; LCCA, left common icantly different from unilateral ACP in shorter cases.14 Table 3
carotid artery; RCCA, right common carotid artery; RSCA, right subclavian summarizes the advantages and disadvantages of ACP and
artery; RVA, right vertebral artery. RCP.21,43,44,55,56

Complications/Long-Term Outcomes
arterial cannula at a flow rate of 10- to-15 mL/kg/min with a
pressure of 50-to-60 mmHg, as measured by an arterial line Aortic arch surgery requiring HCA is associated with many
placed in the right radial artery (Fig 3). Cold oxygenated blood complications, including neurologic, respiratory, and renal. A
flows from the right axillary artery into the right vertebral and summary report from 8 major cardiac surgery centers in the
common carotid arteries. Collateralization to the left cerebral United States, Europe, and Japan found that the risk of
hemisphere can occur via extracranial and leptomeningeal ves-
sels, but primarily occurs through the Circle of Willis. One
study assessing patients before elective aortic arch surgery Table 3
Adjuvant Selective Perfusion: Summary of Advantages and
found that only 27% had a functionally complete Circle of
Disadvantages21,43,44,55,56
Willis. However, most patients with an incomplete Circle of
Willis had a safe variant to allow for unilateral ACP.47 With Adjuvant Perfusion Advantages Disadvantages
proper anastomosis of the graft to the axillary artery, trans- Strategy
duced pressure from the right radial artery should reflect cere- Antegrade Cerebral  Allows for moder-  Risk of atheroscle-
bral perfusion pressure. Bilateral cerebral oximetry is Perfusion ate HCA rotic emboli
monitored, and a decrease of 15% to 20% may trigger an opti-  Physiological  Increased surgical
mization of cerebral protection, including bilateral ACP.48,49 perfusion complexity
 Allows for longer  Possible graft
Although bilateral ACP will address inadequate collateraliza-
deep HCA periods kinking
tion, placing an additional arterial cannula will increase the  Manipulating frag-
risk of cerebral embolization. ile vessels
In contrast to RCP, ACP gained popularity because it Retrograde Cerebral  Flushing cerebral  Venous valves
allowed for moderate HCA. This led to reduced rates of hypo- Perfusion air and emboli could prevent flow
 Cerebral cooling  Cerebral edema
thermia-related organ hypoperfusion, impairment of cerebral  Incomplete
autoregulation, and coagulopathy.50-52 Antegrade cerebral per- perfusion
fusion with oxygenated blood is appealing during circulatory
arrest because it most closely resembles physiologic cerebral Abbreviation: HCA, hypothermic circulatory arrest.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
6 S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112

permanent neurologic injury after aortic arch surgery using However, moderate hypothermia could lead to spinal cord
HCA ranged from 3% to 12%, renal dysfunction from 5% to injury. Kamiya et al. compared moderate and deep HCA lon-
14%, and pulmonary insufficiency from 5% to 39%.57 A meta- ger than 60 minutes, and discovered a trend toward more para-
analysis that included 14 observational studies found that mod- plegia in the moderate group (18% v 0%).65
erate HCA with either ACP or RCP decreased the incidence of Faster rewarming can reduce hypothermia-induced coagulop-
postoperative renal failure compared to deep HCA as long as athy. However, rewarming must be gradual because rapid
the HCA time was <30 minutes.58 rewarming or hyperthermia can lead to cerebral edema, emboli,
Neurologic injury is the most serious adverse effect after the ischemia, or hyperthermic injury.21,22 Hyperthermia-induced neu-
use of HCA, and can range from postoperative cognitive dys- rologic injury mechanisms include increased free-radical produc-
function, which includes confusion, agitation, and delirium, to tion, blood-brain barrier permeability, ischemic depolarizations
stroke, which can be either a transient or an irreversible neuro- with resultant enlarging infarct size, and intracellular acidosis
logic injury. A meta-analysis of 9 studies on aortic arch surgery after reperfusion. In addition, cerebral injury from hyperthermia
by the Collaborative Research group out of Australia compared can ensue from reduced neurotransmitter release and recovery of
neurologic and survival outcomes between 648 patients receiv- adenosine triphosphate.66 Cerebral ischemia can also result from
ing HCA alone and 370 patients receiving HCA with ACP. The uncoupling cerebral flow and oxygen demand, which is observed
different rates of permanent (8% in HCA alone v 6.8% in ACP in hyperthermia. In one study, rewarming increased middle cere-
group) and temporary (13.9% in HCA alone v 11.1% in ACP bral arterial flow by 65% but decreased jugular venous oxygen
group) neurologic deficit were statistically insignificant. How- saturation (SjvO2) by 25%.10,67
ever, overall mortality was significantly reduced from 15.2% to Permanent neurologic deficits after deep HCA are a com-
8.5% when HCA was supplemented with ACP.59 mon major predictor of long-term survival rates.68,69 In
The duration of HCA is the primary prognosticator of mor- patients with neurologic injury, early postoperative mortality
tality and neurologic injury. Pacini et al. found that arrest peri- is markedly increased (18.2%).70 Numerous difficulties arise
ods longer than 40 minutes and femoral cannulation were the when designing clinical trials to compare short and long-term
main predictors of permanent serious complications. Femoral neurologic outcomes in these patients. Ethical concerns about
arterial cannulation reverses native flow and can embolize exposing patients to prolonged arrest times, intraoperative
thoracoabdominal aortic atheroma.60 In another study looking complications, surgical prowess, and the lack of a standard for
at 149 patients approximately 54 days postoperatively, periods neurocognitive assessment are just some of the many prob-
longer than 25 minutes without adjuvant techniques and lems.
advanced age of 60 or greater scored lower in neuropsycholog-
ical testing.61 The same institution investigated 57 patients Anesthetic Management
who received deep HCA with ACP, and found a significant
decline in neurocognition with prolonged arrest times between Anesthetic management of HCA has evolved to address pos-
39 and 83 minutes. However, deep HCA alone between 14 and sible sequelae. However, many of these interventions have not
40 minutes was not associated with cognitive dysfunction. The been validated, secondary to insufficient human research.
authors attributed the contrasting results of the 2 studies to an
evolution of neuroprotection that incorporated selective cere- Therapeutic Interventions
bral perfusion, which reduced HCA durations.62 Another study
examined 656 patients who received deep HCA, and found a Currently, there is no standard pharmacologic practice
hospital survival rate of 88% and a stroke rate of 7%. How- regarding agents, dosing, or timing for HCA. Some institutions
ever, the stroke and mortality risks increased when arrest times use a combination of opioids, barbiturates, lidocaine, steroids,
exceeded 40 and 65 minutes, respectively.28 anticonvulsants, magnesium, and/or mannitol.29,61,62,71 Barbi-
Appoo et al. retrospectively looked at 79 patients undergo- turates decrease CMRO2, CBF, cerebral edema, seizure activ-
ing deep HCA with RCP to determine baseline complication ity, and free-radical formation.71,72 However, animal and
incidences. The incidence of stroke, reexploration for bleed- human studies are inconsistent in showing any benefit of their
ing, and renal disease requiring dialysis were all 3.8%. In-hos- use. Despite this, barbiturates are still used for neuroprotection
pital mortality occurred in 7.6% of patients, 81% of patients in some institutions.73-75 Compared with barbiturates, lido-
left the intensive care unit within 72 hours, and the median caine is reportedly more effective at decreasing CMRO2 by
hospital visit was 7.4 days.63 selectively blocking sodium ion channels in neuronal mem-
Target temperature during HCA also greatly affects clinical branes. However, like barbiturates, human studies have not
outcomes. Many of the previously mentioned studies looked at conclusively conferred cognitive improvements.76,77 Simi-
patients receiving profound (14 C) or deep (14.1-20 C) larly, benzodiazepines and propofol, which induce burst sup-
HCA. One analysis of 413 patients found no significant pression on EEG via gamma-aminobutyric acid inhibition,
increase in neurologic dysfunction in moderate HCA with have shown no or limited clinical use, respectively.21,73 Anti-
ACP longer than 90 minutes. Moderate HCA at 22˚C to 26˚C, convulsants can reduce cerebral metabolism by preventing or
in conjunction with ACP, reduced the rewarming period, treating seizures.71 Magnesium, which blocks voltage-sensi-
decreased CPB time, had less deviation from native cellular tive and N-methyl D-aspartateactivated calcium channels,
activity, and decreased the risk of micro embolism.56,64 has conferred protection against hypoxia in rats.71

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112 7

In animal studies, improvements in cerebral protection have with HCA, and found pain levels and analgesic requirements
been seen with steroids, such as dexamethasone and methyl- to be low, consistent with theoretical expectations. However,
prednisolone. They protect against cerebral ischemia by atten- this study did not have a control group with which to to com-
uating proinflammatory cytokines during and after CPB.78 pare; further research is needed in this area.84
However, human studies have shown limited clinical use of
steroids, increasing the sepsis risk and affecting glucose Monitoring
control.21,78 High-dose steroids, particularly when coupled
with hypothermia-induced insulin resistance, can cause signifi- Patients undergoing aortic arch surgery with HCA are moni-
cant hyperglycemia, worsening neurologic injury secondary to tored with noninvasive monitoring, invasive hemodynamic
tissue lactic acidosis.79 Finally, mannitol is an osmotic diuretic monitoring, TEE, and/or neurophysiologic monitoring. Elec-
that reduces cerebral edema and protects renal function.80 Due trocardiography can detect malignant arrhythmias during cool-
to the lack of established evidence showing the efficacy of ing, such as ventricular fibrillation or significant bradycardia.
these interventions, many institutions have abandoned their Transesophageal echocardiography can ascertain left ventricu-
use altogether. lar distention in the setting of ventricular fibrillation, which
Beyond pharmacologic interventions for neuroprotection, can cause myocardial ischemia. Transesophageal echocardiog-
head surface cooling has been frequently incorporated into raphy also can assess biventricular function, valvular disease,
HCA protocols. Most often done with ice packs, external head aortic disease, and volume status, detect intracardiac air, and
cooling has shown clinical effectiveness in animal studies by evaluate surgical interventions. In addition, it can assist with
decreasing cerebral temperatures, improving CMRO2 recov- venous and aortic cannulation. Transesophageal echocardiog-
ery, and quickening behavioral recovery.81 In nonsurgical raphy can visualize the venous cannula in the hepatic inferior
pediatric patients, in whom a thinner skull may allow for better vena cava and the aortic cannula via the distal tip or Seldinger
conduction of cooling, surface cooling has shown some bene- wire in the proximal descending thoracic aorta to avoid the left
fit.82 However, adult surgical human studies have not been subclavian artery. In one case report, a TEE probe retracted
conclusive, and ice placement has risks. External ice packs can into the hypopharynx was used to visualize bilateral carotid
cause thermal and ocular injury and disrupt cerebral monitors, arteries and internal jugular veins and confirm retrograde flow
including EEG or NIRS.81,82 As the intervention is fairly easy in the veins during RCP.85
and the risks are minor, most institutions employ head surface Temperature monitoring can ensure adequate hypothermia
cooling. for cerebral protection. Temperatures can be measured from
In addition to pharmacologic effects on neurologic out- many sites, including the tympanic membrane, nasopharynx,
comes, hypothermia also greatly affects medications fre- esophagus, urinary bladder, rectum, pulmonary artery, and jug-
quently used by cardiac anesthesiologists. Table 4 summarizes ular venous bulb. Sites more representative of cerebral temper-
the hypothermia-induced changes to the pharmacodynamics of ature include the pulmonary artery, nasopharynx, jugular
commonly used anesthetic agents.83 Opioids, like fentanyl, venous bulb, and tympanic membrane.86-90 The arterial blood
undergo less cytochrome P-450-mediated clearance, resulting outlet temperature has been found to have the best correlation
in increased concentrations.83 Hypothermic circulatory arrest with jugular bulb temperature, and is recommended to be used
depresses neuronal activity, which may suppress nociceptive as a surrogate for cerebral temperature management, with the
stimulation and reduce pain transmission. However, there is nasopharyngeal temperature being second best.20 The rectum
limited pain management research in patients undergoing and bladder, although effective for measuring core tempera-
HCA during cardiac surgery. One study retrospectively ana- tures, are too distal for cerebral temperature monitoring.86,87
lyzed 200 patients undergoing pulmonary endarterectomies Esophageal temperature monitoring has fallen out of favor in
HCA because of its proximity to cardiac structures and an
open thoracic cavity.88 Most institutions use a combination of
Table 4 arterial blood outlet and nasopharyngeal temperature monitor-
Effects of Hypothermia on Common Anesthetic Drugs83 ing as a surrogate for cerebral temperature.
The EEG monitors neuroelectrical activity, which can detect
Drug Effect of Hypothermia
burst suppression, and the time course of the recovery process
Fentanyl  Increased plasma concentration after circulatory arrest can be a sensitive marker of neurologic
 Decreased CYP3A clearance ischemia.91,92 Stecker et al. found that prolonged time to
Midazolam  Increased plasma concentration

recovery of continuous EEG and elevated temperature at
Decreased CYP3A clearance
Propofol  Increased plasma concentration which the EEG first becomes continuous were associated with
 Decreased UDP-glucuronosyltransferase activity an increased risk of postoperative neurologic injury.91 Hypo-
 Decreased clearance thermia <23 C and anesthesia can render EEG interpretation
Rocuronium  Prolonged duration of action impossible, and because EEG reflects brain activity near the
 Decreased clearance

site of electrical lead placement, it cannot detect brain activity
Lidocaine Decreased CYP3A clearance
Isoflurane  Decreased requirements or ischemia in deeper regions such as the hippocampus or basal
 Decreased CYP2E1 metabolism nuclei.92-94 To overcome such limitations, some institutions
supplement SjvO2 to monitor global cerebral oxygenation.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
8 S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112

Jugular venous oxygen saturation is measured by analyzing Table 5

blood sampled from a catheter distally positioned in the jugu- Acid-Base Strategies: Summary of Advantages and Disadvantages21,22,102-107
lar bulb. Jugular venous oxygen saturation indicates the bal- pH Strategy Advantages Disadvantages
ance between cerebral oxygen supply and demand.
On the other hand, its use is limited because it reflects global Alpha-stat  Preserved cerebral  Decreased cerebral
CBF, which may be unaffected by regional cerebral ischemia. autoregulation oxygen tensions
 Preserved cellular enzyme
Low SjvO2 before initiating HCA is associated with adverse activity
neurologic outcomes.95-97 The introduction of NIRS (see pH-stat  Increased cerebral oxygen  Impaired autoregulation
below) as a noninvasive monitor of cerebral oxygen saturation tensions  Impaired CBF
resulted in most institutions abandoning the use of SjvO2.  Cerebral edema
 Microemboli
The bispectral index is often used in place of EEG because
of its noninvasiveness and ease of setup. During cooling, the Abbreviation: CBF, cerebral blood flow.
index will decline biphasically, and most patients have a value
of zero when the temperature reaches 18 C. However, no pro-
spective studies have been conducted with bispectral index in There are 2 different strategies for acid-base regulation dur-
aortic arch surgery with HCA.21,22 Furthermore, it remains ing hypothermia. Alpha-stat management does not correct the
unclear if electrical silence will result in improved outcomes, hypothermia-induced alkaline shift. Autoregulation of the
and the increased cooling and CPB times to document electri- brain and cellular enzymatic activity is preserved by maintain-
cal silence can be deleterious. ing normal acid and blood gas values in the rewarmed blood.
Near-infrared spectroscopy and TCD sonography are com- The preserved autoregulation reduces the risk of cerebral
monly used to monitor cerebral oxygen delivery. Near-infrared edema.22 The pH-stat strategy maintains the temperature-cor-
spectroscopy uses paired optical sensors placed on the scalp to rected pH and pCO2 within a normal range at different body
measure regional brain tissue oxygen saturation continuously. temperatures by adding CO2 through the CPB oxygenator to
Compared with SjvO2, NIRS trends similarly, but has lower overcome hypothermia-induced alkalosis.101 This will disrupt
values during low temperatures, and is not superior to jugular cerebral autoregulation, leading to increased CBF, with a
bulb monitoring.95 Transient drops in regional oxygen satura- greater risk of microemboli and cerebral edema.21,22
tions are unlikely to represent a cerebral event, but persistent However, increased CBF during pH-stat management will
reductions can signal low cerebral perfusion pressure, low increase oxygen tensions and saturations on CPB. Table 5
oxygen content, anemia, decreased cardiac output, or cannula summarizes the advantages and disadvantages of alpha-stat
issues. Harrer et al. showed that upgrading from unilateral to and pH-stat.21,22,102-107 In some studies, alpha-stat manage-
bilateral ACP increased cerebral oxygen saturation from 44% ment caused less disruption in cerebral autoregulation, less
to 63%.48 Although it is limited to a small region of the cere- postoperative cerebral dysfunction, less metabolic disruption,
bral cortex and can be influenced by many hemodynamic fac- better postoperative clinical neurologic assessments, and better
tors, the ease of use and minimal risk have led to greater late survival.102-107 However, comparative studies found no
use.48,49,95 significant difference between either method,108-111 and it will
Transcranial Doppler measures blood flow velocity in the be difficult to determine the superior acid-base strategy with-
middle cerebral artery, and can detect microemboli. Although out randomized trials. Due to the data from the few studies
TCD can assess adequately collateralization of the Circle of mentioned above, most institutions employ alpha-stat manage-
Willis during unilateral ACP, TCD is somewhat difficult to ment for adult HCA cases.
position appropriately and, when malpositioned, may lead to
underestimation of microemboli.98,99 It is rarely used in adults, Coagulopathy Management
as the Doppler window is challenging to find.
Hypothermia-induced coagulopathy is presumably due to a
Acid-Base Management combination of clotting factors and platelet dysfunction,
increased fibrinolysis, and endothelial damage. Analysis of dif-
Hypothermia alters arterial blood gas analysis by increasing ferent coagulation assays has confirmed these assumptions to
the solubility of the respiratory gases CO2 and O2. Increased certain extents dependent on the temperature. Decreases to 33˚
solubility decreases the concentration of free CO2 gas. The C do not significantly affect coagulation enzyme activity, but
resulting drop in arterial PCO2 (PaCO2) increases the pH even do reduce platelet activity, secondary to impaired adhesion.
though total blood CO2 is unchanged. When a hypothermic However, both platelet and enzyme activity are significantly
patient’s blood sample is warmed to 37˚C in the blood gas ana- affected when the hypothermia is <33˚C.112
lyzer, increased free CO2 gas will bring the PaCO2 to the nor- Treatment of HCA-associated coagulopathy can include
mal range of a normothermic individual in an uncorrected antifibrinolytics, blood products, and/or factors. It is dependent
analysis. On the contrary, if the pH is corrected to the patient’s on accurately diagnosing the mechanism of bleeding. Visco-
actual temperature when warmed to 37˚C, the PaCO2 will be elastic testing is ideal because it evaluates the 4 stages of clot
reduced, and the pH will be increased despite similar arterial development: initiation, formation, stabilization, and break-
CO2 content in both samples.100 down. It also isolates components of clot development via

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112 9

Table 6 References
Assay of Viscoelastic Testing113,114
1 Tian DH, Croce B, Hardikar A. Aortic arch surgery. Ann Cardiothorac
Assay Objective
Surg 2013;2:245.
Extrinsic Pathway  Activates tissue factor 2 Klingman RR, Ferraris VA. Resection of aortic arch aneurysms using an
 Assesses for extrinsic pathway factor deficiencies external shunt. Ann Thorac Surg 1994;57:1040–3.
 Assesses for platelet and fibrin contribution to clot 3 Gega A, Rizzo JA, Johnson MH, et al. Straight deep hypothermic arrest:
stability Experience in 394 patients supports its effectiveness as a sole means of
Intrinsic Pathway  Assess for intrinsic pathway factor deficiencies brain preservation. Ann Thorac Surg 2007;84:759–67.
Fibrinogen  Inhibit platelet component of clot strength 4 Wang H, Olivero W, Wang D, et al. Cold as a therapeutic agent. Acta
 Assess fibrinogen polymerization Neurochir (Wien) 2006;148:565–70.
 Assesses for deficiency of fibrinogen and factor XIII 5 Rimmer L, Fok M, Bashir M. The history of deep hypothermic circula-
and indication for cryoprecipitate tory arrest in thoracic aortic surgery. Aorta (Stamford) 2014;2:129–34.
Heparin  Degradation of heparin 6 Guvakov D, Bezinover D, Lomivorotov VV, et al. The "Ice Age" in car-
 Assess for residual heparin and indication for diac surgery: Evolution of the "Siberian" method of brain protection dur-
protamine ing deep hypothermic perfusionless circulatory arrest. J Cardiothorac
Vasc Anesth 2019;33:3366–74.
7 Lewis FJ, Taufic M. Closure of atrial septal defects with the aid of hypo-
thermia; experimental accomplishments and the report of one successful
different assays to discern the mechanism of coagulopathy case. Surgery 1953;33:52–9.
(Table 6).113,114 Ise et al. retrospectively compared thromboe- 8 Barnard CN, Schrire V. The surgical treatment of acquired aneurysm of
lastometry between patients undergoing cardiac surgery with the thoracic aorta. Thorax 1963;18:101–15.
9 Griepp RB, Stinson EB, Hollingsworth JF, et al. Prosthetic replacement
or without HCA. They concluded that HCA affected the plate- of the aortic arch. J Thorac Cardiovasc Surg 1975;70:1051–63.
let aspect of clot strength, and patients had more bleeding and 10 Conolly S, Arrowsmith J, Klein A. Deep hypothermic circulatory arrest.
required more transfusions.113 Continuing Education in Anaesthesia, Critical Care & Pain 2010;10:138–42.
One prospective study by Girdauskas et al. assessed whether 11 Karnatovskaia LV, Wartenberg KE, Freeman WD. Therapeutic hypother-
a transfusion protocol guided by viscoelastic testing could mia for neuroprotection: History, mechanisms, risks, and clinical applica-
tions. Neurohospitalist 2014;4:153–63.
reduce transfusions in patients undergoing aortic surgery with 12 Larsson E, Granath F, Swedenborg J, et al. More patients are treated for
HCA. Patients randomized to the transfusion protocol received nonruptured abdominal aortic aneurysms, but the proportion of women
fresh-frozen plasma, prothrombin complex concentrate, plate- remains unchanged. J Vasc Surg 2008;48:802–7.

lets, fibrinogen, tranexamic acid, and protamine, depending on 13 Olsson C, Thelin S, Stahle E, et al. Thoracic aortic aneurysm and dissec-
their thromboelastometry results. Factor VIIa was adminis- tion: Increasing prevalence and improved outcomes reported in a nation-
wide population-based study of more than 14,000 cases from 1987 to
tered for idiopathic refractory bleeding. They concluded that a 2002. Circulation 2006;114:2611–8.
transfusion protocol guided by viscoelastic testing significantly 14 Isselbacher EM, Preventza O, Hamilton Black J 3rd, et al.
reduced blood and fresh-frozen plasma administration.115 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic
Disease: A report of the American Heart Association/American College
of Cardiology Joint Committee on Clinical Practice Guidelines. Circula-
Conclusions tion 2022;146:e334–482.
15 Clouse WD, Hallett JW Jr, Schaff HV, et al. Acute aortic dissection: Pop-
ulation-based incidence compared with degenerative aortic aneurysm
Hypothermic circulatory arrest was an important advance- rupture. Mayo Clin Proc 2004;79:176–80.
ment to allow complex aortic arch surgery to take place. How- 16 DeMartino RR, Sen I, Huang Y, et al. Population-based assessment of the
ever, circulatory arrest and intentional hypothermia come with incidence of aortic dissection, intramural hematoma, and penetrating
significant risks. The other major advancement in aortic sur- ulcer, and its associated mortality from 1995 to 2015. Circ Cardiovasc
Qual Outcomes 2018;11:e004689.
gery was selective cerebral perfusion via RCP and ACP to 17 Patel PD, Arora RR. Pathophysiology, diagnosis, and management of aor-
obviate these risks. The anesthetic management of patients tic dissection. Ther Adv Cardiovasc Dis 2008;2:439–68.
undergoing HCA can be complicated. Nevertheless, cardiac 18 Stanson AW, Kazmier FJ, Hollier LH, et al. Penetrating atherosclerotic
anesthesiologists must stay abreast of evolving surgical techni- ulcers of the thoracic aorta: Natural history and clinicopathologic correla-
ques and their implications as more research is done in the tions. Ann Vasc Surg 1986;1:15–23.
19 Al-Atassi T, Khoynezhad A. Indications for aortic arch intervention.
field. Semin Cardiothorac Vasc Anesth 2016;20:259–64.
20 Engelman R, Baker RA, Likosky DS, et al. The Society of Thoracic Sur-
geons, the Society of Cardiovascular Anesthesiologists, and the American
Declaration of Competing Interest Society of ExtraCorporeal Technology: Clinical practice guidelines for
cardiopulmonary bypasstemperature management during cardiopulmo-
None. nary bypass. J Cardiothorac Vasc Anesth 2015;29:1104–13.
21 Qu JZ, Kao LW, Smith JE, et al. Brain protection in aortic arch surgery:
An evolving field. J Cardiothorac Vasc Anesth 2021;35:1176–88.
22 Patel PM, Chen EP. Optimal brain protection in aortic arch surgery.
Acknowledgments Indian J Thorac Cardiovasc Surg 2022;38:36–43.
23 Grigore AM, Grocott HP, Mathew JP, et al. The rewarming rate and
The authors are grateful to Jill Gregory for the medical illus- incrased peak temperature alter neurocognitive outcome after cardiac sur-
tration work featured in this article. gery. Anesth Analg 2002;94:4–10.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
10 S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112

24 Englum BR, Andersen ND, Husain AM, et al. Degree of hypothermia in 47 Smith T, Jafrancesco G, Surace G, et al. A functional assessment of the
aortic arch surgery - optimal temperature for cerebral and spinal protec- circle of Willis before aortic arch surgery using transcranial Doppler. J
tion: Deep hypothermia remains the gold standard in the absence of ran- Thorac Cardiovasc Surg 2019;158:1298–304.
domized data. Ann Cardiothorac Surg 2013;2:184–93. 48 Harrer M, Waldenberger FR, Weiss G, et al. Aortic arch surgery using
25 McCullough JN, Zhang N, Reich DL, et al. Cerebral metabolic suppres- bilateral antegrade selective cerebral perfusion in combination with near-
sion during hypothermic circulatory arrest in humans. Ann Thorac Surg infrared spectroscopy. Eur J Cardiothorac Surg 2010;38:561–7.
1999;67:1895–921. 49 Lewis C, Parulkar SD, Bebawy J, et al. Cerebral neuromonitoring during
26 Yan TD, Bannon PG, Bavaria J, et al. Consensus on hypothermia in aortic cardiac surgery: A critical appraisal with an emphasis on near-infrared
arch surgery. Ann Cardiothorac Surg 2013;2:163–8. spectroscopy. J Cardiothorac Vasc Anesth 2018;32:2313–22.
27 Stecker MM, Cheung AT, Pochettino A, et al. Deep hypothermic circula- 50 Griepp RB. Cerebral protection during aortic arch surgery. J Thorac Car-
tory arrest: I. Effects of cooling on electroencephalogram and evoked diovasc Surg 2001;121:425–7.
potentials. Ann Thorac Surg 2001;71:14–21. 51 Zierer A, Aybek T, Risteski P, et al. Moderate hypothermia (30 degrees
28 Svensson LG, Crawford ES, Hess KR, et al. Deep hypothermia with cir- C) for surgery of acute type A aortic dissection. Thorac Cardiovasc Surg
culatory arrest. Determinants of stroke and early mortality in 656 patients. 2005;53:74–9.
J Thorac Cardiovasc Surg 1993;106:19–31. 52 Tian DH, Wan B, Bannon PG, et al. A meta-analysis of deep hypothermic
29 Harrington DK, Lilley JP, Rooney SJ, et al. Nonneurologic morbidity and circulatory arrest versus moderate hypothermic circulatory arrest with selec-
profound hypothermia in aortic surgery. Ann Thorac Surg 2004;78:596– tive antegrade cerebral perfusion. Ann Cardiothorac Surg 2013;2:148–58.
601. 53 Perreas K, Samanidis G, Thanopoulos A, et al. Antegrade or retrograde
30 Angeloni E, Benedetto U, Takkenberg JJ, et al. Unilateral versus bilateral cerebral perfusion in ascending aorta and hemiarch surgery? A propen-
antegrade cerebral protection during circulatory arrest in aortic surgery: sity-matched analysis. Ann Thorac Surg 2016;101:146–52.
A meta-analysis of 5100 patients. J Thorac Cardiovasc Surg 54 Spielvogel D, Tang GH. Selective cerebral perfusion for cerebral protec-
2014;147:60–7. tion: What we do know. Ann Cardiothorac Surg 2013;2:326–30.
31 Chau KH, Friedman T, Tranquilli M, et al. Deep hypothermic circulatory 55 Stein LH, Elefteriades JA. Protecting the brain during aortic surgery: An
arrest effectively preserves neurocognitive function. Ann Thorac Surg enduring debate with unanswered questions. J Cardiothorac Vasc Anesth
2013;96:1553–9. 2010;24:316–21.
32 Ziganshin BA, Elefteriades JA. Deep hypothermic circulatory arrest. Ann 56 Khaladj N, Shrestha M, Meck S, et al. Hypothermic circulatory arrest
Cardiothorac Surg 2013;2:303–15. with selective antegrade cerebral perfusion in ascending aortic and aortic
33 Lemole GM, Strong MD, Spagna PM, et al. Improved results for dissect- arch surgery: A risk factor analysis for adverse outcome in 501 patients. J
ing aneurysms. Intraluminal sutureless prosthesis. J Thorac Cardiovasc Thorac Cardiovasc Surg 2008;135:908–14.
Surg 1982;83:249–55. 57 Moon MR, Miller DC. Aortic arch replacement for dissection. Oper
34 Ueda Y, Miki S, Kusuhara K, et al. Deep hypothermic systemic circula- Techn Thorac Cardiovasc Surg 1999;4:33–57.
tory arrest and continuous retrograde cerebral perfusion for surgery of 58 Cao L, Guo X, Jia Y, et al. Effect of deep hypothermic circulatory arrest
aortic arch aneurysm. Eur J Cardiothorac Surg 1992;6:36–42. versus moderate hypothermic circulatory arrest in aortic arch surgery on
35 Reich DL, Uysal S, Ergin MA, et al. Retrograde cerebral perfusion as a postoperative renal function: A systematic review and meta-analysis. J
method of neuroprotection during thoracic aortic surgery. Ann Thorac Am Heart Assoc 2020;9:e017939.
Surg 2001;72:1774–82. 59 Tian DH, Wan B, Bannon PG, et al. A meta-analysis of deep hypothermic
36 Bavaria JE, Pochettino A. Retrograde cerebral perfusion (RCP) in aortic circulatory arrest alone versus with adjunctive selective antegrade cere-
arch surgery: Efficacy and possible mechanisms of brain protection. bral perfusion. Ann Cardiothorac Surg 2013;2:261–70.
Semin Thorac Cardiovasc Surg 1997;9:222–32. 60 Pacini D, Di Marco L, Leone A, et al. Antegrade selective cerebral perfu-
37 Safi HJ, Miller CC 3rd, Lee TY, et al. Repair of ascending and transverse sion and moderate hypothermia in aortic arch surgery: Clinical outcomes
aortic arch. J Thorac Cardiovasc Surg 2011;142:630–3. in elderly patients. Eur J Cardiothorac Surg 2012;42:249–53.
38 Lau C, Gaudino M, Iannacone EM, et al. Retrograde cerebral perfusion is 61 Reich DL, Uysal S, Sliwinski M, et al. Neuropsychologic outcome after
effective for prolonged circulatory arrest in arch aneurysm repair. Ann deep hypothermic circulatory arrest in adults. J Thorac Cardiovasc Surg
Thorac Surg 2018;105:491–7. 1999;117:156–63.
39 Oohara K, Usui A, Murase M, et al. Regional cerebral tissue blood flow 62 Uysal S, Lin HM, Fischer GW, et al. Selective cerebral perfusion for tho-
measured by the colored microsphere method during retrograde cerebral racic aortic surgery: Association with neurocognitive outcome. J Thorac
perfusion. J Thorac Cardiovasc Surg 1995;109:772–9. Cardiovasc Surg 2012;143:1205–12.
40 Usui A, Hotta T, Hiroura M, et al. Retrograde cerebral perfusion through 63 Appoo JJ, Augoustides JG, Pochettino A, et al. Perioperative outcome in
a superior vena caval cannula protects the brain. Ann Thorac Surg adults undergoing elective deep hypothermic circulatory arrest with retro-
1992;53:47–53. grade cerebral perfusion in proximal aortic arch repair: Evaluation of pro-
41 Usui A, Oohara K, Liu TL, et al. Comparative experimental study tocol-based care. J Cardiothorac Vasc Anesth 2006;20:3–7.
between retrograde cerebral perfusion and circulatory arrest. J Thorac 64 Di Eusanio M, Schepens MA, Morshuis WJ, et al. Antegrade selective
Cardiovasc Surg 1994;107:1228–36. cerebral perfusion during operations on the thoracic aorta: Factors influ-
42 Sakurada T, Kazui T, Tanaka H, et al. Comparative experimental study of encing survival and neurologic outcome in 413 patients. J Thorac Cardio-
cerebral protection during aortic arch reconstruction. Ann Thorac Surg vasc Surg 2002;124:1080–6.
1996;61:1348–54. 65 Kamiya H, Hagl C, Kropivnitskaya I, et al. The safety of moderate hypo-
43 Dresser LP, McKinney WM. Anatomic and pathophysiologic studies of thermic lower body circulatory arrest with selective cerebral perfusion: A
the human internal jugular valve. Am J Surg 1987;154:220–4. propensity score analysis. J Thorac Cardiovasc Surg 2007;133:501–9.
44 K€unzli A, Zingg PO, Z€ und G, et al. Does retrograde cerebral perfusion via 66 Grocott HP, Mackensen GB, Grigore AM, et al. Postoperative hyperther-
superior vena cava cannulation protect the brain? Eur J Cardiothorac Surg mia is associated with cognitive dysfunction after coronary artery bypass
2006;30:906–9. graft surgery. Stroke 2002;33:537–41.
45 Katz MG, Khazin V, Steinmetz A, et al. Distribution of cerebral flow 67 von Knobelsdorff G, H€anel F, Werner C, et al. Jugular bulb oxygen satu-
using retrograde versus antegrade cerebral perfusion. Ann Thorac Surg ration and middle cerebral blood flow velocity during cardiopulmonary
1999;67:1065–9. bypass. J Neurosurg Anesthesiol 1997;9:128–33.
46 Yilik L, Emrecan B, Kestelli M, et al. Direct versus side-graft cannulation 68 Gatti G, Benussi B, Curro P, et al. The risk of neurological dysfunctions
of the right axillary artery for antegrade cerebral perfusion. Tex Heart Inst after deep hypothermic circulatory arrest with retrograde cerebral perfu-
J 2006;33:310–5. sion. J Stroke Cerebrovasc Dis 2017;26:3009–19.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112 11

69 Kr€ahenb€uhl ES, Immer FF, Stalder M, et al. Temporary neurological dys- 91 Stecker MM, Cheung AT, Pochettino A, et al. Deep hypothermic circula-
function after surgery of the thoracic aorta: A predictor of poor outcome tory arrest: II. Changes in electroencephalogram and evoked potentials
and impaired quality of life. Eur J Cardiothorac Surg 2008;33:1025–9. during rewarming. Ann Thorac Surg 2001;71:22–8.
70 Stier GR, Verde EW. The postoperative care of adult patients exposed to 92 Tan SZ, Singh S, Austin NJ, et al. Duration of deep hypothermic circula-
deep hypothermic circulatory arrest. Semin Cardiothorac Vasc Anesth tory arrest for aortic arch surgery: Is it a myth, fiction, or scientific leap? J
2007;11:77–85. Cardiovasc Surg (Torino) 2022;63:243–53.
71 Svyatets M, Tolani K, Zhang M, et al. Perioperative management of deep 93 Hagl C, Khaladj N, Karck M, et al. Hypothermic circulatory arrest during
hypothermic circulatory arrest. J Cardiothorac Vasc Anesth ascending and aortic arch surgery: The theoretical impact of different
2010;24:644–55. cerebral perfusion techniques and other methods of cerebral protection.
72 Harris B, Manecke GR Jr, Niemann J, et al. Deep hypothermia and the Eur J Cardiothorac Surg 2003;24:371–8.
vascular response to thiopental. J Cardiothorac Vasc Anesth 94 Stecker MM, Keselman I. Monitoring cardiac and ascending aortic proce-
2006;20:678–83. dures. Handb Clin Neurol 2022;186:395–406.
73 Dewhurst AT, Moore SJ, Liban JB. Pharmacological agents as cerebral 95 Leyvi G, Bello R, Wasnick JD, et al. Assessment of cerebral oxygen bal-
protectants during deep hypothermic circulatory arrest in adult thoracic ance during deep hypothermic circulatory arrest by continuous jugular
aortic surgery. A survey of current practice. Anaesthesia 2002;57:1016– bulb venous saturation and near-infrared spectroscopy. J Cardiothorac
21. Vasc Anesth 2006;20:826–33.
74 Nussmeier NA, Arlund C, Slogoff S. Neuropsychiatric complications 96 Keenan JE, Wang H, Ganapathi AM, et al. Electroencephalography dur-
after cardiopulmonary bypass: Cerebral protection by a barbiturate. Anes- ing hemiarch replacement with moderate hypothermic circulatory arrest.
thesiology 1986;64:165–70. Ann Thorac Surg 2016;101:631–7.
75 Zaidan JR, Klochany A, Martin WM, et al. Effect of thiopental on neuro- 97 Griepp RB, Ergin MA, McCullough JN, et al. Use of hypothermic circu-
logic outcome following coronary artery bypass grafting. Anesthesiology latory arrest for cerebral protection during aortic surgery. J Card Surg
1991;74:406–11. 1997;12:312–21.
76 Wang D, Wu X, Li J, et al. The effect of lidocaine on early postoperative 98 Sakahashi H, Hashimoto A, Aomi S, et al. Transcranial Doppler measure-
cognitive dysfunction after coronary artery bypass surgery. Anesth Analg ment of middle cerebral artery blood flow during continuous retrograde
2002;95:1134–41. cerebral perfusion[article in Japanese] Nihon Kyobu Geka Gakkai Zasshi
77 Mathew JP, Mackensen GB, Phillips-Bute B, et al. Randomized, double- 1994;42:1851–7.
blinded, placebo controlled study of neuroprotection with lidocaine in 99 Karadeniz U, Erdemli O, Ozatik MA, et al. Assessment of cerebral blood
cardiac surgery. Stroke 2009;40:880–7. flow with transcranial Doppler in right brachial artery perfusion patients.
78 Shum-Tim D, Tchervenkov CI, Jamal AM, et al. Systemic steroid pre- Ann Thorac Surg 2005;79:139–46.
treatment improves cerebral protection after circulatory arrest. Ann 100 Andritsch RF, Muravchick S, Gold MI. Temperature correction of arterial
Thorac Surg 2001:721465–72. blood-gas parameters: A comparative review of methodology. Anesthesi-
79 Strong AJ, Fairfield JE, Monteiro E, et al. Insulin protects cognitive function in ology 1981;55:311–6.
experimental stroke. J Neurol Neurosurg Psychiatry 1990;53:847–53. 101 Kurth CD, O’Rourke MM, O’Hara IB. Comparison of pH-stat and alpha-
80 Manetta F, Mullan CW, Catalano MA. Neuroprotective strategies in stat cardiopulmonary bypass on cerebral oxygenation and blood flow in
repair and replacement of the aortic arch. Int J Angiol 2018;27:98–109. relation to hypothermic circulatory arrest in piglets. Anesthesiology
81 Zhurav L, Wildes TS. Pro: Topical hypothermia should be used during 1998;89:110–8.
deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth 102 Patel RL, Turtle MR, Chambers DJ, et al. Alpha-stat acid-base regulation
2012;26:333–6. during cardiopulmonary bypass improves neuropsychologic outcome in
82 Grocott HP, Andreiw A. Con: Topical head cooling should not be used patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc
during deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth Surg 1996;111:1267–79.
2012;26:337–9. 103 Venn GE, Patel RL, Chambers DJ. Cardiopulmonary bypass: Periopera-
83 Zhou J, Poloyac SM. The effect of therapeutic hypothermia on drug tive cerebral blood flow and postoperative cognitive deficit. Ann Thorac
metabolism and response: Cellular mechanisms to organ function. Expert Surg 1995;59:1331–5.
Opin Drug Metab Toxicol 2011;7:803–16. 104 Patel RL, Turtle MR, Chambers DJ, et al. Hyperperfusion and cerebral
84 Gimenez-Mila M, Videla S, Jenkins D, et al. Acute Pain and Analgesic dysfunction. Effect of differing acid-base management during cardiopul-
Requirements After Pulmonary Endarterectomy With Deep Hypothermic monary bypass. Eur J Cardiothorac Surg 1993;7:457–64.
Circulatory Arrest. J Cardiothorac Vasc Anesth 2016;30:993–6. 105 Kancir CB, Madsen T. Effect of acid-base management with or without
85 Waje ND, Maddali MM, Nadarajan K. Transpharyngeal imaging with carbon dioxide on plasma phosphate concentration during and after hypo-
transesophageal echocardiography as an adjunct for optimizing retrograde thermic cardiopulmonary bypass. Scand J Thorac Cardiovasc Surg
cerebral perfusion. J Cardiothorac Vasc Anesth 2017;31:987–92. 1992;26:151–5.
86 Stone JG, Young WL, Smith CR, et al. Do standard monitoring sites 106 Stephan H, Weyland A, Kazmaier S, et al. Acid-base management during
reflect true brain temperature when profound hypothermia is rapidly hypothermic cardiopulmonary bypass does not affect cerebral metabolism
induced and reversed? Anesthesiology 1995;82:344–51. but does affect blood flow and neurological outcome. Br J Anaesth
87 Eshel GM, Safar P. Do standard monitoring sites affect true brain temper- 1992;69:51–7.
ature when hyperthermia is rapidly induced and reversed. Aviat Space 107 Damberg A, Carino D, Charilaou P, et al. Favorable late survival after
Environ Med 1999;70:1193–6. aortic surgery under straight deep hypothermic circulatory arrest. J
88 Akata T, Setoguchi H, Shirozu K, et al. Reliability of temperatures mea- Thorac Cardiovasc Surg 2017;154:1831–9;.e1.
sured at standard monitoring sites as an index of brain temperature during 108 Bellinger DC, Wypij D, du Plessis AJ, et al. Developmental and neuro-
deep hypothermic cardiopulmonary bypass conducted for thoracic aortic logic effects of alpha-stat versus pH-stat strategies for deep hypothermic
reconstruction. J Thorac Cardiovasc Surg 2007;133:1559–65. cardiopulmonary bypass in infants[published correction appears in J
89 Camboni D, Philipp A, Schebesch KM, et al. Accuracy of core tempera- Thorac Cardiovasc Surg 2001;121:893] J Thorac Cardiovasc Surg
ture measurement in deep hypothermic circulatory arrest. Interact Cardio- 2001;121:374–83.
vasc Thorac Surg 2008;7:922–4. 109 Baraka AS, Baroody MA, Haroun ST, et al. Effect of alpha-stat versus
90 Amir G, Ramamoorthy C, Riemer RK, et al. Deep brain hyperthermia pH-stat strategy on oxyhemoglobin dissociation and whole-body oxygen
while rewarming from hypothermic circulatory arrest. J Card Surg consumption during hypothermic cardiopulmonary bypass. Anesth Analg
2009;24:606–10. 1992;74:32–7.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
12 S. Ghia et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 112

110 Badner NH, Murkin JM, Lok P. Differences in pH management and pul- 113 Ise H, Kitahara H, Oyama K, et al. Hypothermic circulatory arrest
satile/nonpulsatile perfusion during cardiopulmonary bypass do not influ- induced coagulopathy: Rotational thromboelastometry analysis[published
ence renal function. Anesth Analg 1992;75:696–701. correction appears in Gen Thorac Cardiovasc Surg 2020;68:1224] Gen
111 Engelhardt W, Dierks T, Pause M, et al. Early cerebral functional out- Thorac Cardiovasc Surg 2020;68:754–61.
come after coronary artery bypass surgery using different acid-base man- 114 G€orlinger K, Perez-Ferrer A, Dirkmann D, et al. The role of evidence-
agement during hypothermic cardiopulmonary bypass. Acta Anaesthesiol based algorithms for rotational thromboelastometry-guided bleeding
Scand 1996;40:457–65. management. Korean J Anesthesiol 2019;72:297–322.
112 Wolberg AS, Meng ZH, Monroe DM 3rd, et al. A systematic evaluation 115 Girdauskas E, Kempfert J, Kuntze T, et al. Thromboelastometrically guided
of the effect of temperature on coagulation enzyme activity and platelet transfusion protocol during aortic surgery with circulatory arrest: A prospec-
function. J Trauma 2004;56:1221–8. tive, randomized trial. J Thorac Cardiovasc Surg 2010;140:1117–24;.e2.

Downloaded for Anonymous User (n/a) at Pontifical Catholic University of Chile from ClinicalKey.com by Elsevier on October
11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.