Temperature Management During Circulatory Arrest in Cardiac Surgery

Abstract

Surgery for complex aortic pathologies such as dissections, interrupted aortic arch and aneurysms involving aortic arch, remains one of the most technically and strategically demanding intervention for cardiac surgeons. Despite the continuous development of new surgical and perfusion techniques these interventions are still associated with significant mortality and morbidity. The introduction in the Seventies of deep hypothermia made possible aortic arch surgery with a defined safe period of brain ischemia (usually 30–40 minutes) during circulatory arrest. About 20 years later the use of selective cerebral perfusion associated with deep hypothermia, made possible excellent neuroprotection for longer periods of circulatory arrest. However deep hypothermia, even if protective from ischemia, has a lot of adverse effects: increases systemic inflammatory response and organ dysfunctions, impairs ions concentration, induces arrhythmias and increases risk of severe postoperative bleeding. The possibility of selective cerebral perfusion, avoiding adverse effects of deep hypothermia and eventually reduce operation time, brought surgeons to use moderate to mild hypothermia or even normothermia. However there is no pre-clinical data supporting this practice and adverse outcomes due to inadequate temperature management (target temperature and rewarming rate) are probably underreported. Indeed, physiology and pathology of deep hypothermia are not completely understood and the ideal perfusion technique and the best temperature management are to this day still missing.

Introduction

During aortic arch surgery, interruption of blood flow through cardiopulmonary bypass (CPB) is requested, the result is diffuse ischemic hypoxic injury for all body organs.

The main complication after induced circulatory arrest of interest is neurologic damage. Three main strategies for cerebral protection of patients undergoing extensive aortic surgery have been developed and studied so far. These are straight deep hypothermic circulatory arrest (DHCA), retrograde cerebral perfusion (RCP), and antegrade cerebral perfusion (ACP). The possible superiority of one of these three techniques has been an ongoing topic for debate and research of new perfusion techniques, and definition of the best temperature management is always in progress.

Furthermore, the recent use of selective cerebral perfusion brought to the application of higher temperature during circulatory arrest applying moderate or mild hypothermia. This practice drew attention to a new problem: risk of ischemic damage of abdominal viscera and spinal cord during moderate or mild hypothermic circulatory arrest (MHCA) (Table 1) (Marx, 2010).

Table 1.

Stages of Hypothermia

Level of hypothermia	Temperature (°C)
Mild	35.9–33.0
Moderate	32.9–28.0
Deep	27.9–21.0
Profound	≤20.9

Marx, 2010.

Deep Hypothermic Circulatory Arrest

The interruption of cerebral circulation leads to several biochemical and histological changes. Anaerobic metabolism becomes the only source of ATP synthesis, resulting in lactate accumulation and acidosis. Ischemia leads to inflammation and recruitment of leucocytes that release proteolytic enzymes, activation of neuronal nitric oxide, and creation of free radicals, which can damage the cell proteins and cell membrane. Apoptosis and cerebral edema occur due to ionic changes and impairment of the blood–brain barrier. This is followed by a reperfusion injury with restoration of cerebral blood flow. Hypothermia is a significant modifier of cerebral flow and metabolism (Michenfelder et al., 1968, 1973). Studies have confirmed that there is a 6–7% drop in metabolism for every 1°C drop below 37°C. Oxygen consumption is reduced from 2.90 mL/g/min at normothermia to 0.90 mL/g/min at 25°C, and at 20°C, it is reduced to one-fifth of normothermic values, with little effect of going lower (McCullogh et al., 1999). Several other factors play a role in neural tissue integrity at low temperatures, such as changes in oxygen delivery, and cerebral autoregulation. Moreover, hypothermia may have a protective effect reducing excitotoxicity of locally released glutamate (Van Hemelrijck et al., 2003), decreasing the formation of oxygen free radicals, and suppressing intracellular calcium influx (Bickler et al., 1994; McCullogh et al., 1999) (Table 2).

Table 2.

Safe Period with Low Risk of Neurological Complications at Different Grades of Hypothermia

Temperature (°C)	Brain Safe CA (minute)
37 (normothermia)	5
30 (moderate)	8–10
25 (deep)	12–15
20 (profound)	17–24
15 (profound)	25–38
10 (profound)	36–62

McCullogh et al., 1999.

CA, Circulatory arrest.

Hypothermia has been recognized as a key tool of the cardiac surgeon since the pioneer era (Bigelow et al., 1950). Isolated cases in adults using DHCA and CPB were attempted in the 1960s for aortic aneurysm surgery (Borst et al., 1964; Lillehei et al., 1969). Thereafter, DHCA has been used in aortic arch surgery as an effective cerebral protective technique for more than three decades and has been refined by Griepp et al. (1975). Although hypothermia has proven to be a good protection strategy for many organs, a time-dependent cascade of events resulting in brain cell injury is initiated with the beginning of circulatory arrest (Ergin et al., 1982). Moreover, DHCA facilitates the performance of complex cardiac procedures in adults and children, providing the opportunity to prepare a completely bloodless field to allow unrestricted visualization of great vessels without the distortion or damage of vascular clamps and without overfill operative field with cannulae (Strauch et al., 2004; Gega et al., 2007; Griepp et al., 2013).

Clinical studies suggested that, in the absence of cerebral perfusion, the safe duration in deep hypothermia would be limited to 40–60 minutes beyond which the occurrence of stroke is prohibitive (Svensson et al., 1993; Ergin et al., 1994).

More recently, neuropsychological tests showed that more than 25 minutes of DHCA duration and advanced age were significant predictors of poor performance in examinations of memory and fine-motor function (Ergin et al., 1999).

Commonly, surgeons use temperatures between 12°C and 25°C during DHCA (Asou et al., 1996), the majority employ temperatures between 18°C and 19°C (Gega et al., 2007), but the evidence to support any particular degree is controversial (Cook et al., 2006; Sanioglu et al., 2009).

Dumfarth et al. (2013) asserted that hypothermia alone was sufficient during aortic arch surgery: in the few strokes that did occur with DHCA, computed tomographic evaluation revealed that two-thirds were embolic (and therefore not protection related) and the remaining one third appeared to be hypoperfusion related (and potentially protection related). The mean DHCA time was 31 minutes (range, 10–66 minutes); in patients with DHCA times that exceeded 40 minutes, the stroke rate increased significantly to 13.1%.

Concerns about the increased mortality and risk of neurologic deficit led to implementation of adjuncts, such as ACP and RCP, which might enhance the safety of the DHCA technique (Bachet, 2010).

Perfusion Strategies for Cerebral Protection During DHCA

Antegrade cerebral perfusion

ACP refers to perfusion of brain with oxygenated blood independently of the rest of the body. There are several advantages of ACP, including its potential to prolong the safe time of circulatory arrest, to improve cerebral cooling, and its potential application with moderate hypothermia. The concept of perfusing brain in an antegrade manner during aortic surgery was initially presented by DeBakey et al. (1957). Despite the successful treatment of the reported patient, results in the following years, utilizing this technique, were disappointing and it was abandoned. A novel interest in antegrade perfusion was made by Bachet et al. (1999) who first used hypothermic cerebral perfusion.

Recently, ACP has become the method of choice for cerebral protection during aortic arch surgery in many centers. However, the technical details of ACP remain controversial, including the choice of cannulation site, unilateral or bilateral ACP, perfusion pressure during ACP, and temperature management: the ideal temperature of both the perfusate for ACP itself and the core temperature during selective ACP (SACP) with systemic circulatory arrest remain a concern. With the clinical introduction of ACP, deep hypothermia became not essential for neuroprotection, which led to a growing tendency in increasing the body temperature during circulatory arrest to avoid coagulopathy or organ dysfunction after the extended period needed to reach deep hypothermia and the slow rewarming before weaning from CPB (Kazui et al., 2001; Di Eusanio et al., 2003; Panos et al., 2006).

There are two main surgical options for ACP. Nonselective ACP (NSACP) refers to cannulation of right axillary artery or innominate artery with left-hemispheric perfusion dependent on a patent Circle of Willis. The technique of axillary artery cannulation for both CPB and ACP during the arrest was popularized in 1990 by Sabik et al. (1995) and this has now become a main strategy among aortic surgeons. Advantages of axillary artery cannulation include its use as an access for CPB and relative freedom from dissection and atherosclerotic disease, thus decreasing incidence of atheroemboli. It may also be considered safer (Moizumi et al., 2005), less time consuming, and may avoid direct cannulation of aortic branches, which might be involved in aortic pathology (Svensson et al., 2004; Stavros et al., 2009; Wong et al., 2010). However, potential complications of axillary artery cannulation include insufficient flow, inadequate right upper limb perfusion, lymphocele, and brachial plexus injury.

SACP involves selective cannulation of both left common carotid artery and innominate artery directly or through a tube graft. SACP allowed increased performance of total arch replacement and reduced periprocedural mortality and morbidity in patients with aortic arch aneurysms and those with acute aortic dissection, furthermore, selective cerebral perfusion time had no significant impact on the outcome (Kazui et al., 1992, 2000).

Di Eusanio et al. (2003) reviewed 588 patients who had operations on the thoracic aorta using SACP. The extent of aortic repair and SACP time was not statistically correlated with an increased risk of hospital mortality, temporary neurologic dysfunction (TND), or permanent neurologic dysfunction (PND). The drawbacks of this approach include the needed dissection of these key vessels, which may lead to vessel injury or embolization and the inconvenience of added cannulae in the operative field (Matalanis et al., 2003).

However, clinical reports of ACP have generally been very positive and ACP became the preferred technique of cerebral protection because other techniques did not provide satisfactory cerebral protection and were associated with harmful effects of deep hypothermia (Coselli et al., 1997; Ye et al., 1997; Westaby et al., 1999). On the other hand, DHCA/SACP has been found to be superior to DHCA alone for preventing cerebral injury during operations on the aortic arch (Strauch et al., 2004). Spielvogel et al. (2005) concluded that the optimal cerebral protection strategy for total arch replacement would seem to be one relying on hypothermic antegrade selective cerebral perfusion.

Halkos et al. (2009) reported on a retrospective review of 271 patients who had aortic surgery using DHCA with (n = 205) or without (n = 66) SACP. Operative mortality occurred in 12.1% (33/271) of patients: 8.8% (18/205) in patients with SACP versus 22.7% (15/66) in those with DHCA alone (p = 0.003). TND occurred in 5.9% (15/255) of patients: 4.5% (9/198) in SACP versus 10.5% (6/57) in DHCA alone (p = 0.09). Stroke occurred in 4.3% (11/255) of patients with no difference between the groups. SACP was associated with shorter intensive care unit and ventilator times and fewer renal and pulmonary complications.

Leshnower et al. (2010) retrospectively reported on 344 patients who underwent hemiarch reconstruction and 68 patients who underwent total arch replacement with right axillary artery cannulation. The operative mortality was 7.0%, the incidence of PND and TND were 3.6% and 5.1%, respectively. In the adjusted analysis, DHCA with unilateral selective brain perfusion was not found to be an independent predictor of mortality, PND, TND, or renal failure requiring dialysis.

Unilateral ACP through axillary artery offers brain and visceral organ protection at least equal to that of bilateral ACP and might be advantageous reducing the incidence of embolism arising from surgical manipulation on arch vessels. The concept of SACP for aortic arch surgery using a warm perfusate and a core temperature of 30°C is described in a study from two institutions and can be considered safe, straightforward, and reproducible and might help reduce the CPB time and hypothermia-related side effects (Zierer et al., 2012).

In conclusion, most of the series suggest ACP for patients who need longer cerebral protection because it could provide the luxury of time, allowing the appropriate repair of complicated arch aneurysms. Cerebral and body perfusion through axillary and femoral artery combined cannulation or through SACP may provide more time for the surgeon and better protection for the brain and visceral organs, which is especially important for surgical teams during the learning curve.

Retrograde cerebral perfusion

This technique was proposed based on the success of use of retrograde flushing through the superior vena cava (SVC) after massive air embolism during CPB (Mills et al., 1980). With RCP, SVC is perfused with cold blood (12–15°C) at low pressure (20–30 mmHg, flow rates 250–800 mL/min) with blood exiting the head through the carotid arteries. This approach was first introduced during aortic surgery by Lemole et al. (1982) and popularized in the 1990s by Ueda et al. (1990, 1992).

There are several potential true and theoretical advantages of RCP. The technique provides the opportunity for thorough deairing of vessels of the arch. Cerebral cooling is facilitated and toxin removal occurs. It may also remove solid emboli from the arterial branches of the arch (Elmistekawy and Rubens, 2011). Finally, it avoids manipulation of the atheromatous arch vessels and allows removal of some cannulae from the surgical field providing cerebral flow sufficient to support cerebral metabolism and maintaining cerebral hypothermia (Usui et al., 1992; Anttila et al., 2000; Apostolakis and Akinosoglou, 2008).

Although RCP was reported to expel air emboli, it is now well known that the pressure necessary for this causes brain edema and may aggravate cerebral injury (Yerlioglu et al., 1995; Juvonen et al., 1998).

Other disadvantages include the scanty evidence that blood reaches the cerebral target, an assumption that may provide false confidence; the blood returning to the aortic arch was only 3–10% of the amount given through the retrograde perfusion cannula, more than 90% is deviated through the azygos to the SVC or entrapped in the cerebral venous sinuses (Deeb et al., 1995; Ye et al., 1998).

Discussion

ACP versus RCP versus DHCA

Since when the three techniques described have become routine in cardiac surgery, several clinical studies that compare DHCA and the different techniques of brain perfusion were performed; however, until today is still not clear if a procedure is superior to the others.

When compared with other clinical neurologic outcomes, such as TND, PND, and all-cause deaths within 30 days, ACP and RCP provide similar protection effectiveness. Frist et al. (1986) found that a combination of selective cerebral perfusion with hypothermia allowed the use of much lower flow rates and hypothermic SACP afforded better cerebral protection from global ischemia than DHCA alone or DHCA and RCP.

ACP was reported to afford the best cerebral protection, but RCP was reported to provide clear improvement compared to DHCA (Midulla et al., 1994). Recently, RCP has lost its popularity because it did not sufficiently prolong the safe period of DHCA. Less than 60 minutes of RCP was reported to be tolerated with a minimal risk of brain complication (Usui et al., 1996).

Several studies have reported that PND is more likely to occur after ACP because of embolism and TND was more likely to occur after RCP because of global ischemia and longer cerebral ischemic time (Ergin et al., 1999; Khaladj et al., 2008).

Hagl et al. (2001) compared 717 patients undergoing arch surgery: there was no influence of perfusion technique on the incidence of stroke. However, ACP resulted in a significant reduction in the incidence on TND. Okita performed a prospective study of aortic arch replacement in 60 consecutive patients, alternately assigned RCP and ACP protection strategies: no difference in mortality was noted between groups nor was there a difference between groups in the stroke rate, however, there was a significantly higher incidence of TND in the RCP group (Okita et al., 2001).

RCP has been compared to no perfusion during DHCA cases; there were no difference in postarrest oxygen extraction, glucose extraction, or jugular bulb PO2 between the groups (Bonser et al., 2002).

Apostolakis et al. (2008) reviewed 48 consecutive patients who underwent arch replacement under DHCA 16–20°C. ACP was used in 23 patients and RCP in 25 patients. No significant differences were found between the groups in PND and mortality. The incidence of TND was 16.0% for the ACP group and 43.50% for the RCP group (p = 0.04). ACP was also found to be related with earlier extubation and shorter ICU stay and hospitalization.

Apaydin et al. (2009) reviewed 161 patients who required cerebral protection longer than 25 minutes. DHCA alone was used in 48 patients, RCP in 94, and ACP in 19. The overall mortality was 15.5% (25/161) and did not differ among the perfusion groups. There was no difference in the incidence of overall neurological events, TND, or major stroke among the groups.

Milewski et al. (2010) retrospectively reviewed 776 cases using RCP/DHCA (in 682 patients) and ACP/DHCA (in 94 patients): there was no statistically significant difference in the composite endpoint of mortality, neurologic event, acute myocardial infarction, PND, TND, or renal failure between techniques for aortic reconstruction times less than 45 minutes.

Hu et al. (2014) found no difference in TND and PND between the RCP group and the ACP group, suggesting that both techniques provide acceptable cerebral outcomes. Because ACP and RCP worked equally well with DHCA, it seems that hypothermia was the key ingredient and the type of perfusion was not essential.

Deep versus moderate hypothermia

Protective effects of DHCA are already well known, however, the idea that deep hypothermia is a totally safe method to prevent ischemic damage has to be reconsidered (Table 3).

Table 3.

Potential Negative Effects of Deep Hypothermia

Apparatus	Effect
Cardiovascular effects	• ↑arterious pressure
	• bradycardia
	• ↓Co
	• hypovolemia
	• arrhythmias
Drug clearance	• ↓drugs clearance
Electrolytic disorders	• hypomagnesemia
	• hypokalemia
	• hypocalcemia
	• hypofosfatemia
Metabolic effects	• hyperglycemia, insulin resistance, and decreased insulin production
Coagulation	• platelets and coagulation factors dysfunction
Infections	• ↓white blood cells
	• ↑infections risk
Gastrointestinal system	• Slow gastrointestinal motility
	• pancreatitis
Kidney	• ↑diuresis
	• Renal tubular dysfunction

In hypothermia, seric levels, drug clearance decrease, and the effects of some drugs can change.

In particular, benzodiazepines and opioids can accumulate during hypothermia, complicating a correct neurological evaluation of postoperatory TND (Tortorici et al., 2007).

An electrolytic disorder is very common during the induction of hypothermia and rewarming leading to an increased risk of arrhythmia; therefore, changes in temperature should be very slow, giving time for the kidneys to eliminate ions in excess. Hyperglycemia during hypothermia is frequent and is correlated to the increase of insulin resistance and reduction of insulin release by pancreas. An inadequate management of glycemia could worsen the brain ischemic damage and increase the risk of postoperative infections, which are already higher during and after hypothermia because of reduction of immunitary protection.

Duration of DHCA longer than 25 minutes causes TND, fine motor deficits, and prolonged hospital stay (Ergin et al., 1994; Reich et al., 1999). Prolonged circulatory arrest, even in deep hypothermia, may be associated with organ dysfunction, such as postoperative renal impairment, coagulation disorders, and significant postoperative bleeding (Haverich and Angl, 2003). However, scientific evidence for this claim is inadequate and dubious, in effect postoperative bleeding seems to be more related to operation time and the use of prolonged extracorporeal circulation than the level of hypothermia.

DHCA with ACP may result in endothelial damage and cerebral edema due to increased vascular resistance until deep temperatures with a risk of increased intracerebral pressures (Ehrlich et al., 2002).

TND or PND occurs more frequently following prolonged DHCA with durations >40 minutes, and DHCA longer than 65 minutes is associated with a significantly increased postoperative mortality, a finding that is confounded by the fact that the duration of DHCA is frequently linked to the complexity of the procedure (McCullough et al.,1999).

Despite the absence of confirmative experimental data for safety of higher body core temperatures, encouraged by the success of ACP, more and more clinical centers tolerate moderate-to-mild (28–35°C) hypothermia during arch repair (Luehr et al., 2014). The aim is to limit and reduce potential negative effects of hypothermia. Küçüker et al. (2005) reported a unilateral antegrade ACP perfusion technique through the right brachial artery in conjunction with moderate hypothermia under 26°C with excellent neurologic outcomes.

Panos et al. (2006) reported a series of 25 patients suffering from acute Type A dissection who were successfully perfused by unilateral ACP through axillary artery and distal arrest at a rectal temperature of 25–27°C for 40 minutes.

Pacini et al. (2007) published results of 305 aortic arch operations either with DHCA (<22°C) or hypothermia of up to 26°C with an average ACP time of 60 minutes, no differences could be found in 30-day mortality (12.7% vs. 13.8%), PND (3.1% vs. 1.7%; p = 0.72) and TND (7.9% vs. 8.6%). In another recent study, the same authors reported excellent outcomes of 95 elderly patients (≥75 years) treated with profound ACP of 20°C and circulatory arrest at 25°C (Pacini et al., 202). In 2012, Urbanski et al. published their results of 270 hemiarch repairs and 77 total arch replacements, using ACP and moderate-to-mild circulatory arrest of up to 31.5°C (range 26.0–35.0°C). Postoperatively, 5 of 347 patients required dialysis and only 1 patient suffered from bowel ischemia; 30-day mortality (0.9%) and neurological complications (PND 2.3% and TND 0.9%) were remarkably low, with no occurrence of paraplegia. In this article, the authors suggested the possibility of routine use of moderate-to-MHCA and SACP during aortic arch surgery. Leshnower et al. (2012) retrospectively compared the outcome after elective and emergent hemiarch replacements with ACP for 25 minutes at deep and moderate temperatures (24.3°C vs. 28.6°C), finding a significantly reduced rate of PND (2.5% vs. 7.2%) in the moderate group and no significant differences in bleeding, TND, or renal failure (Leshnower et al., 2012).

Despite good outcome found by many authors, use of moderate hypothermia during circulatory arrest revealed a new important problem: moderate-to-mild perfusion strategies avoid deeper temperatures and shorten extracorporeal circulation times, but also increase risks for the spinal cord and nonperfused organs of the lower body in case of a prolonged operation time. Kamiya et al. (2007) was the first to report on the possible danger of neurological spinal complications during prolonged circulatory arrest (>60 minutes) and moderate hypothermia at 28°C with SACP. The authors found a sixfold increase in mortality and ischemic spinal cord injury, and paraplegia rate of 18%. In comparison, the paraplegia rate in patients operated on deep hypothermia (20–24°C) was 0%. Zierer et al. (2011) reported that PND and TND occurred in 6% and 5% in 245 patients undergoing moderate HCA (30.5°C) and ACP for an average of 38 minutes. Postoperatively, increased levels of lactate, creatinine, and liver enzymes were monitored, but no bowel ischemia or liver failure occurred; however, dialysis-dependent renal failure occurred in 7% of patients.

The recent inclination to perform moderate-to-MHCA leads up to a significant risk of ischemic spinal cord injury causing a wide spectrum of neurological damage from temporary paraparesis to irreversible permanent paraplegia. Fortunately, the incidence of postoperative neurological and visceral complications following ACP and deep-to-moderate HCA of up to 30 minutes remains rare. In 2003, the Mount Sinai group demonstrated that spinal cord ischemic tolerance is significantly prolonged when cooling from normothermia to mild hypothermia (32°C) before aortic cross-clamping (Strauch et al., 2004) (Table 4). These results demonstrated that moderate hypothermia during HCA should suffice to protect the spinal cord from ischemic injury for a quite long period.

Table 4.

Safe Period with Low Risk of Ischemic Spinal Cord Damage at Different Grades of Hypothermia

Temperature (°C)	Spinal Cord Safe CA (minute)
37 (normothermia)	20
32 (moderate)	50
28 (moderate)	75
20 (deep)	120

Strauch et al., 2004.

Visceral ischemic damage during elective aortic arch surgery at deep hypothermic temperatures remain an uncommon event because the ischemic tolerance of the abdominal viscera most likely exceeds spinal cord ischemic tolerance at a given core temperature.

Tagaki et al. (2002, 2005) used an aortic balloon occlusion catheter with a perfusion lumen for protection of lower body during distal anastomosis in aortic arch repair; in the author's opinion, distal aortic perfusion avoids the need for deep hypothermia. Klodell et al. (2004) perfused distal aorta at a bladder temperature of 18°C and suggested that this technique allowed continuation of cerebral protection, with an added benefit of maintaining antegrade flow to the distal aorta, spinal cord, viscera, and lower extremities.

Della Corte et al. (2006) used thoracoabdominal perfusion during aortic arch surgery by descending endoluminal cannulation or femoral artery cannulation. Overall mortality and PND rates did not significantly differ compared with operations performed without lower body perfusion; they found a significantly lower incidence of respiratory and renal failure as well as shorter durations of mechanical ventilation, intensive care, and hospital stay.

Clinically, it seems that between abdominal viscera, the kidneys are most sensitive to ischemia, followed by the liver and bowel. The use of distal perfusion may reduce the incidence of end-organ complications to visceral organs and the spinal cord, particularly in more extensive and time-consuming aortic arch operations.

Conclusions

Several adjunctive factors must be considered when comparing clinical studies related to temperature management during HCA, including the use of topical external cooling of the head, optimized acid-base management, pumps prime modifications, pharmacologic interventions, and leukocyte depletion. Another extremely important variable related to neurologic morbidity relates to strategies of cooling and rewarming.

RCP has experienced profound criticism recently, and it seems to not sufficiently extend the safe period during DHCA.

ACP is favorable for patients who need longer cerebral protection because it could provide the luxury of time, allowing for appropriate repair of complicated arch aneurysms, which is especially important for surgical teams during the learning curve.

Especially, for short DHCA (25–30 minutes), straight DHCA seems to provide an excellent cerebral protection and surgical results and for urgent operations for acute type-A dissection in which the arrest time can be anticipated to be short for an open distal anastomosis. Hypothermia is by far the most effective modality for preservation of tissue integrity during unavoidable periods of interrupted blood flow. However, hypothermia has negative effects too; so, to decrease these negative effects recently, mainly with the help of ACP, many clinicians are using moderate-to-mild hypothermia. A lot of studies show good results using moderate hypothermia during HCA, especially when it is associated with selective perfusion techniques of brain and lower body.

The great number of studies and publications on this argument demonstrates a great interest from clinicians in this field. However, the amount of data obtained with different techniques, different temperature, and perfusion management may be confusing. Development of an experimental model could help defining the best temperature and perfusion management with a best comprehension of physiologic principles and limitations of HCA.

Surgeons and all operatory room team should know the different perfusion and temperature management techniques to choose the best solution for every patient and every situation, and, if it is necessary, change the operation program to face unexpected circumstances.

Guide lines established on expert consensus are strongly required. Optimal temperature and perfusion management in aortic arch surgery have to be defined and guaranteed to patients, especially in relatively simple aortic arch surgery, elective or urgent, when the time of circulatory arrest could be foreseen.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

Anttila

, Pokela

, Kiviluoma

, Mäkiranta

, Hirvonen

, Juvonen

. Is maintained cranial hypothermia the only factor leading to improved outcome after retrograde cerebral perfusion: an experimental study with a chronic porcine model. J Thorac Cardiovasc Surg, 2000; 119:1021–1029.

Apaydin

, Islamoglu

, Askar

, Engin

, Posacioglu

, Yagdi

, Ayik

. Immediate clinical outcome after prolonged periods of brain protection: retrospective comparison of hypothermic circulatory arrest, retrograde, and antegrade perfusion. J Card Surg, 2009; 24:486–489.

Apostolakis

, Akinosoglou

. The methodologies of hypothermic circulatory arrest and of antegrade and retrograde cerebral perfusion for aortic arch surgery. Ann Thorac Cardiovasc Surg, 2008; 14:138–148.

Apostolakis

, Koletsis

, Dedeilias

, Kokotsakis

, Sakellaropoulos

, Psevdi

, Bolos

, Dougenis

. Antegrade versus retrograde cerebral perfusion in relation to postoperative complications following aortic arch surgery for acute aortic dissection type A. J Card Surg, 2008; 23:480–487.

Asou

, Kado

, Imoto

, Shiokawa

, Tominaga

, Kawachi

, Yasui

. Selective cerebral perfusion technique during aortic arch repair in neonates. Ann Thorac Surg, 1996; 61:1546–1548.

Bachet

. What is the best method for brain protection in surgery of the aortic arch? Selective antegrade cerebral perfusion. Cardiol Clin, 2010; 28:389–401.

Bachet

, Guilmet

, Goudot

, Dreyfus

, Delentdecker

, Brodaty

, Dubois

. Antegrade cerebral perfusion with cold blood: a 13-year experience. Ann Thorac Surg, 1999; 67:1874–1878.

Bickler

, Buck

, Hansen

. Effects of isoflurane and hypothermia on glutamate receptor-mediated calcium influx in brain slices. Anesthesiology, 1994; 81:1461–1469.

Bigelow

, Callaghan

, Hopps

. General hypothermia for experimental intracardiac surgery. Ann Surg, 1950; 132:531–539.

10.

Bonser

, Wong

, Harrington

, Pagano

, Wilkes

, Clutton-Brock

, Faroqui

. Failure of retrograde cerebral perfusion to attenuate metabolic changes associated with hypothermic circulatory arrest. J Thorac Cardiovasc Surg, 2002; 123:943–950.

11.

Borst

, Schaudig

, Rudolph

. Arterovenous fistula of the aortic arch: repair during deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg, 1964; 48:443–447.

12.

Cook

, Gao

, Macnab

, Fedoruk

, Day

, Janusz

. Aortic arch reconstruction: safety of moderate hypothermia and antegrade cerebral perfusion during systemic circulatory arrest. J Card Surg, 2006; 21:158–164.

13.

Coselli

, LeMaire

. Experience with retrograde cerebral perfusion during proximal aortic surgery in 290 patients. J Cardiac Surg, 1997; 12:322–325.

14.

DeBakey

, Crawford

, Cooley

, Morris

. Successful resection of fusiform aneurysm of aortic arch with replacement by homograft. Surg Gynecol Obstet, 1957; 105:657–664.

15.

Deeb

, Jenkins

, Bolling

, Brunsting

, Williams

, Quint

, Deeb

. Retrograde cerebral perfusion during hypothermic circulatory arrest reduces neurologic morbidity. J Thorac Cardiovasc Surg, 1995; 109:259–268.

16.

Della Corte

, Scardone

, Romano

, Amarelli

, Biondi

, De Santo

, De Feo

, Nappi

, Cotrufo

. Aortic arch surgery: thoracoabdominal perfusion during antegrade cerebral perfusion may reduce postoperative morbidity. Ann Thorac Surg, 2006; 81:1358–1364.

17.

Di Eusanio

, Schepens

, Morshuis

, Dossche

, Di Bartolomeo

, Pacini

, Pierangeli

, Kazui

, Ohkura

, Washiyama

. Brain protection using antegrade selective cerebral perfusion: a multicenter study. Ann Thorac Surg, 2003; 76:1181–1188.

18.

Di Eusanio

, Wesselink

RMJ

, Morshuis

, Dossche

, Schepens

. Deep hypothermic circulatory arrest and antegrade selective cerebral perfusion during ascending aorta-hemiarch replacement: a retrospective comparative study. J Thorac Cardiovasc Surg, 2003; 125:849–854.

19.

Dumfarth

, Ziganshin

, Tranquilli

, Elefteriades

. Cerebral protection in aortic arch surgery: hypothermia alone suffices. Tex Heart Inst J, 2013; 40:564–565.

20.

Ehrlich

, McCullough

, Zhang

, Weisz

, Juvonen

, Bodian

, Griepp

. Effect of hypothermia on cerebral blood flow and metabolism in the pig. Ann Thorac Surg, 2002; 73:191–197.

21.

Elmistekawy

, Rubens

. Deep hypothermic circulatory arrest: alternative strategies for cerebral perfusion. A review article. Perfusion, 2011; 26 Suppl 1:27–34.

22.

Ergin

, Griepp

, Lansman

, Galla

, Levy

, Griepp

. Hypothermic circulatory arrest and other methods of cerebral protection during operations on the thoracic aorta. J Card Surg, 1994; 9:525–537.

23.

Ergin

, O'Connor

, Guinto

, Griepp

. Experience with profound hypothermia and circulatory arrest in the treatment of aneurysms of the aortic arch. Aortic arch replacement for acute arch dissections. J Thorac Cardiovasc Surg, 1982; 84:649–655.

24.

Ergin

, Uysal

, Reich

, Apaydin

, Lansman

, McCullough

, Griepp

. Temporary neurological dysfunction after deep hypothermic circulatory arrest: a clinical marker of long-term functional deficit. Ann Thorac Surg, 1999; 67:1887–1890.

25.

Frist

, Baldwin

, Starnes

, Stinson

, Oyer

, Miller

, Jamieson

, Mitchell

, Shumway

. A reconsideration of cerebral perfusion in aortic arch replacement. Ann Thorac Surg, 1986; 42:273–281.

26.

Gega

, Rizzo

, Johnson

, Tranquilli

, Farkas

, Elefteriades

. Straight deep hypothermic arrest: experience in 394 patients supports its effectiveness as a sole means of brain preservation. Ann Thorac Surg, 2007; 84:759–766.

27.

Griepp

, Di Luozzo

. Hypothermia for aortic surgery. J Thorac Cardiovasc Surg, 2013; 145:S56–S58.

28.

Griepp

, Stinson

, Hollingsworth

, Buehler

. Prosthetic replacement of the aortic arch. J Thorac Cardiovasc Surg, 1975; 70:1051–1063.

29.

Hagl

, Ergin

, Galla

, Lansman

, McCullough

, Spielvogel

, Sfeir

, Bodian

, Griepp

. Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients. J Thorac Cardiovasc Surg, 2001; 121:1107–1121.

30.

Halkos

, Kerendi

, Myung

, Kilgo

, Puskas

, Chen

. Selective antegrade cerebral perfusion via right axil-lary artery cannulation reduces morbidity and mortality after proximal aortic surgery. J Thorac Cardiovasc Surg, 2009; 138:1081–1089.

31.

Haverich

, Hagl

. Organ protection during hypothermic circulatory arrest. J Thorac Cardiovasc Surg, 2003; 125:460–462.

32.

, Wang

, Ren

, Wu

, Zhang

, Hu

. Similar cerebral protective effectiveness of antegrade and retrograde cerebral perfusion combined with deep hypothermia circulatory arrest in aortic arch surgery: a meta-analysis and systematic review of 5060 patients. J Thorac Cardiovasc Surg, 2014; 148:544–560.

33.

Juvonen

, Zhang

, Wolfe

, Weisz

, Bodian

, Shiang

, McCullough

, Griepp

. Retrograde cerebral perfusion enhances cerebral protection during prolonged hypothermic circulatory arrest: a study in a chronic porcine model. Ann Thorac Surg, 1998; 66:38–50.

34.

Kamiya

, Hagl

, Kropivnitskaya

, Bothig

, Kallenbach

, Khaladj

, Martens

, Haverich

, Karck

. The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: a propensity score analysis. J Thorac Cardiovasc Surg, 2007; 133:501–509.

35.

Kazui

, Inoue

, Yamada

, Komatsu

. Selective cerebral perfusion during operation for aneurysms of the aortic arch: a reassessment. Ann Thorac Surg, 1992; 53:109–114.

36.

Kazui

, Inoue

, Yamada

, Komatsu

. Total arch replacement using aortic arch branched grafts with the aid of antegrade selective cerebral perfusion. Ann Thorac Surg, 2000; 70:3–8.

37.

Kazui

, Washiyama

, Muhammad

, Terada

, Yamashita

, Takinami

. Improved results of atherosclerotic arch aneurysm operations with a refined technique. J Thorac Cardiovasc Surg, 2001; 121:491–499.

38.

Khaladj

, Shrestha

, Meck

, Peterss

, Kamiya

, Kallenbach

, Winterhalter

, Hoy

, Haverich

, Hagl

. Hypothermic circulatory arrest with selective antegrade cerebral perfusion in ascending aortic and aortic arch surgery: a risk factor analysis for adverse outcome in 501 patients. J Thorac Cardiovasc Surg, 2008; 135:908–914.

39.

Klodell

, Hess

, Beaver

, Clark

, Martin

. Distal aortic perfusion during aortic arch reconstruction: another tool for the aortic surgeon. Ann Thorac Surg, 2004; 78:196–198.

40.

Küçüker

, Ozatik

, Saritaş

, Taşdemir

. Arch repair with unilateral antegrade cerebral perfusion. Eur J Cardiothorac Surg, 2005; 27:638–643.

41.

Lemole

, Strong

, Spagna

, Karmilowicz

. Improved results for dissecting aneurysms. Intraluminal sutureless prosthesis. J Thorac Cardiovasc Surg, 1982; 83:249–255.

42.

Leshnower

, Myung

, Kilgo

, Vassiliades

, Vega

, Thourani

, Puskas

, Guyton

, Chen

. Moderate hypothermia and unilateral selective antegrade cerebral perfusion: a contemporary cerebral protection strategy for aortic arch surgery. Ann Thorac Surg, 2010; 90:547–554.

43.

Leshnower

, Myung

, Thourani

, Halkos

, Kilgo

, Puskas

, Chen

. Hemiarch replacement at 28°C: an analysis of mild and moderate hypothermia in 500 patients. Ann Thorac Surg, 2012; 93:1910–1916.

44.

Lillehei

, Todd

Jr , Levy

, Ellis

. Partial cardiopulmonary bypass, hypothermia, and total circulatory arrest. A lifesaving technique for ruptured mycotic aortic aneurysms, ruptured left ventricle, and other complicated cardiac pathology. J Thorac Cardiovasc Surg, 1969; 58:530–544.

45.

Luehr

, Bachet

, Mohr

, Etz

. Modern temperature management in aortic arch surgery: the dilemma of moderate hypothermia. Eur J Cardiothorac Surg, 2014; 45:27–39.

46.

Marx

. Rosen's Emergency Medicine: Concepts and Clinical Practice. 7th edn. Philadelphia, PA: Mosby Elsevier, 2010.

47.

Matalanis

, Hata

, Buxton

. A retrospective comparative study of deep hypothermic circulatory arrest, retrograde, and antegrade cerebral perfusion in aortic arch surgery. Ann Thorac Cardiovasc Surg, 2003; 9:174–179.

48.

McCullough

, Zhang

, Reich

, Juvonen

, Klein

, Spielvogel

, Ergin

, Griepp

. Cerebral metabolic suppression during hypothermic circulatory arrest in humans. Ann Thorac Surg, 1999; 67:1895–1899; discussion 919–921.

49.

Michenfelder

, Theye

. Hypothermia: effect on canine brain and whole-body metabolism. Anesthesiology, 1968; 29:1107–1111.

50.

Michenfelder

, Theye

. Cerebral protection by thiopental during hypoxia. Anesthesiology, 1973; 39:510–517.

51.

Midulla

, Gandsas

, Sadeghi

, Mezrow

, Yerlioglu

, Wang

, Wolfe

, Ergin

, Griepp

. Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model. J Cardiovasc Surg, 1994; 9:560–574.

52.

Milewski

, Pacini

, Moser

, Moeller

, Cowie

, Szeto

, Woo

, Desai

, Di Marco

, Pochettino

, Di Bartolomeo

, Bavaria

. Retrograde and antegrade cerebral perfusion: results in short elective arch reconstructive times. Ann Thorac Surg, 2010; 89:1448–1457.

53.

Mills

, Ochsner

. Massive air embolism during cardiopulmonary bypass. Causes, prevention, and management. J Thorac Cardiovasc Surg, 1980; 80:708–717.

54.

Moizumi

, Motoyoshi

, Sakuma

, Yoshida

. Axillary artery cannulation improves operative results for acute type a aortic dissection. Ann Thorac Surg, 2005; 80:77–83.

55.

Okita

, Minatoya

, Tagusari

, Ando

, Nagatsuka

, Kitamura

. Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion. Ann Thorac Surg, 2001; 72:72–79.

56.

Pacini

, Di Marco

, Leone

, Di Bartolomeo

, Sodeck

, Englberger

, Carrel

, Czerny

. Antegrade selective cerebral perfusion and moderate hypothermia in aortic arch surgery: clinical outcomes in elderly patients. Eur J Cardiothorac Surg, 2012; 42:249–253.

57.

Pacini

, Leone

, Di Marco

, Marsilli

, Sobaih

, Turci

, Masieri

, Di Bartolomeo

. Antegrade selective cerebral perfusion in thoracic aorta surgery: safety of moderate hypothermia. Eur J Cardiothorac Surg, 2007; 31:618–622.

58.

Panos

, Murith

, Bednarkiewicz

, Khatchatourov

. Axillary cerebral perfusion for arch surgery in acute type A dissection under moderate hypothermia. Eur J Cardiothorac Surg, 2006; 29:1036–1039.

59.

Reich

, Uysal

, Sliwinski

, Ergin

, Kahn

, Konstadt

. Neuropsychologic outcome after deep hypothermic circulatory arrest inadults. J Thorac Cardiovasc Surg, 1999; 117:156–163.

60.

Sabik

, Lytle

, McCarthy

, Cosgrove

. Axillary artery: an alternative site of arterial cannulation for patients with extensive aortic and peripheral vascular disease. J Thorac Cardiovasc Surg, 1995; 109:885–890.

61.

Sanioglu

, Sokullu

, Arslan

, Sargin

, Yilmaz

, Ozay

, Tokoz

, Bilgen

. Comparison of unilateral antegrade cerebral perfusion at 16 degrees C and 22 degrees C systemic temperature. Heart Surg Forum, 2009; 12:E65–E69.

62.

Spielvogel

, Halstead

, Meier

, Kadir

, Lansman

, Shahani

, Griepp

. Aortic arch replacement using a trifurcated graft: simple, versatile, and safe. Ann Thorac Surg, 2005; 80:90–95.

63.

Stavros

, Siminelakis

, Baikoussis

, Papadopoulos

, Beis

. Axillary artery cannulation for cardiopulmonary bypass during surgery on the ascending aorta and arch. J Card Surg, 2009; 24:301–304.

64.

Strauch

, Lauten

, Spielvogel

, Rinke

, Zhang

, Weisz

, Bodian

, Griepp

. Mild hypothermia protects the spinal cord from ischemic injury in a chronicporcine model. Eur J Cardiothorac Surg, 2004; 25:708–715.

65.

Strauch

, Spielvogel

, Lauten

, Galla

, Lansman

, McMurtry

, Griepp

. Technical advances in total aortic arch replacement. Ann Thorac Surg, 2004; 77:581–589.

66.

Strauch

, Spielvogel

, Lauten

, Lansman

, McMurtry

, Bodian

, Griepp

. Axillary artery cannulation: routine use in ascending aorta and aortic arch replacement. Ann Thorac Surg, 2004; 78:103–108.

67.

Svensson

, Blackstone

, Rajeswaran

, Sabik

, Lytle

, Gonzalez-Stawinski

, Varvitsiotis

, Banbury

, McCarthy

, Pettersson

, Cosgrove

. Does the arterial cannulation site for circulatory arrest influence stroke risk?. Ann Thorac Surg, 2004; 78:1274–1284.

68.

Svensson

, Crawford

, Hess

, Coselli

, Raskin

, Shenaq

, Safi

. Deep hypothermia with circulatory arrest. Determinants of stroke and early mortality in 656 patients. J Thorac Cardiovasc Surg, 1993; 106:19–28.

69.

Takagi

, Matsuno

. Distal aortic perfusion during aortic arch repair. Ann Thorac Surg, 2005; 80:1159; author reply 1159–1160.

70.

Takagi

, Mori

, Iwata

, Umeda

, Matsuno

, Hirose

. Aortic balloon occlusion catheter with perfusion lumen for protection of lower body during distal anastomosis in aortic arch repair. J Thorac Cardiovasc Surg, 2002; 123:1006–1008.

71.

Tortorici

, Kochanek

, Poloyac

. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system (review). Crit Care Med, 2007; 35:2196–2204.

72.

Ueda

, Miki

, Kusuhara

, Okita

, Tahata

, Yamanaka

. Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch, utilizing circulatory arrest and retrograde cerebral perfusion. J Cardiovasc Surg, 1990; 31:553–558.

73.

Ueda

, Miki

, Kusuhara

, Okita

, Tahata

, Yamanaka

. Deep hypothermic systemic circulatory arrest and continuous retrograde cerebral perfusion for surgery of aortic arch aneurysm. Eur J Cardiothorac Surg, 1992; 6:36–41.

74.

Urbanski

, Lenos

, Bougioukakis

, Neophytou

, Zacher

, Diegeler

. Mild-to-moderate hypothermia in aortic arch surgery using circulatory arrest: a change of paradigm?. Eur J Cardiothorac Surg, 2012; 41:185–191.

75.

Usui

, Abe

, Murase

. Early clinical results of retrograde cerebral perfusion for aortic arch operations in Japan. Ann Thorac Surg, 1996; 62:94–103.

76.

Usui

, Hotta

, Hirouraa

, Murase

, Maeda

, Koyamaa

, Tanaka

, Takeuchi

, Yasuura

, Watanabe

, Abe

. Retrograde cerebral perfusion through a superior vena caval cannula protects the brain. Ann Thorac Surg, 1992; 53:47–53.

77.

Van Hemelrijck

, Vermijlen

, Hachimi-Idrissi

, Sarre

, Ebinger

, Michotte

. Effect of resuscitative mild hypothermia on glutamate and dopamine release, apoptosis and ischaemic brain damage in the endothelin-1 rat model for focal cerebral ischaemia. J Neurochem, 2003; 87:66–75.

78.

Westaby

, Katsumata

, Vaccari

. Arch and descending aortic aneurysms: influence of perfusion technique on neurological outcome. Eur J Cardiothorac Surg, 1999; 15:180–185.

79.

Wong

, Coselli

, Palmero

, Bozinovski

, Carter

, Murariu

, LeMaire

. Axillary artery cannulation in surgery for acute or subacute ascending aortic dissections. Ann Thorac Surg, 2010; 90:731–737.

80.

, Ryner

, Kozlowski

, Yang

, Del Bigio

, Sun

, Donnelly

, Summers

, Salerno

, Somorjai

, Saunders

, Deslauriers

. Retrograde cerebral perfusion results in flow distribution abnormalities and neuronal damage. A magnetic resonance imaging and histopathological study in pigs. Circulation, 1998; 98:II313–II318.

81.

, Yang

, Del Bigio

, Summers

, Jackson

, Somorjai

, Salerno

, Deslauriers

. Retrograde cerebral perfusion provides limited distribution of blood to the brain: a study in pigs. J Thorac Cardiovasc Surg, 1997; 114:660–665.

82.

Yerlioglu

, Wolfe

, Mezrow

, Weisz

, Midulla

, Zhang

, Shiang

, Bodian

, Griepp

. The effect ofretrograde cerebral perfusion after particulate embolization to the brain. J Thorac Cardiovasc Surg, 1995; 110:1470–1484.

83.

Zierer

, Detho

, Dzemali

, Aybek

, Moritz

, Bakhtiary

. Antegrade cerebral perfusion with mild hypothermia for aortic arch replacement: single-center experience in 245 consecutive patients. Ann Thorac Surg, 2011; 91:1868–1873.

84.

Zierer

, El-Sayed Ahmad

, Papadopoulos

, Moritz

, Diegeler

, Urbanski

. Selective antegrade cerebral perfusion and mild (28°C–30°C) systemic hypothermic circulatory arrest for aortic arch replacement: results from 1002 patients. J Thorac Cardiovasc Surg, 2012; 144:1042–1049.