Cerebral Protection during Repair of Type A Aortic Dissection

Abstract

Surgical repair of type A aortic dissection includes most often a period of hypothermic circulatory arrest to allow inspection of the disease within the aortic arch and perform the most appropriate distal repair. Clinical methods of cerebral protection have considerably evolved during the last decades, starting with isolated hypothermic circulatory arrest without or with medicamentous protection and combined later with different methods of cerebral perfusion. One category aims at significantly reducing or suppressing the metabolic demands of the cerebral tissue. The second provides the brain with some metabolic requirements despite the exclusion of the supra-aortic branches from the aortic arch and can be summarized as perfusion of the brain through the arterial or venous network, in either an antegrade or a retrograde fashion. Numerous clinical studies have reported excellent results following antegrade perfusion of the brain. This represents most probably the best method to preserve the integrity of the senso-motoric functions and cognitive faculties, particularly in frail patients and in those requiring a more complex surgical procedure in the setting of acute type A dissection.

1. Introduction

The history of hypothermic circulatory arrest (HCA) started with the first attempts at surgical repair of the aortic arch by Cooley in 1955, while DeBakey described in 1957 a technique using cardiopulmonary bypass (CPB) and cerebral perfusion [1]. In addition to the usual CPB circuit, the system included four pumps and perfusion lines for both carotid and coronary arteries. Despite fair results, this technique did not receive much attention because of the complex configuration of the CPB. Later, Borst used deep hypothermia and circulatory arrest for the surgical repair of a rare pathology of the aortic arch, namely an arteriovenous fistula [2].

A complete resection of the total arch with consecutive prosthetic replacement was performed in 1966 in France [3]. In 1975, Griepp published four cases of aortic arch aneurysms successfully operated on using deep hypothermia associated with total circulatory arrest [4]. His technique represented a breakthrough in the concept of aortic arch surgery because it aimed at reducing as much as possible the need for oxygen and metabolites during the period of the circulatory arrest while the absence of clamps and blood in the operative field greatly simplified the procedure. The concept of cold cerebral perfusion of the brain combined with moderate hypothermia of the body was attempted by the group of Guilmet while Kazui published a similar method in which the cerebral perfusion and the main CPB were performed both at moderate hypothermia [5, 6]. At a pretty similar time, Ueda proposed a technique of retrograde perfusion of the brain through the superior vena cava and right jugular vein using deep hypothermia [7].

Since these first steps, a remarkable development has been made and HCA combined with cerebral perfusion can now be considered as a routine procedure with reliable and reproducible results in experienced institutions. A large scientific activity was necessary to understand the protective characteristics of hypothermia and the methods of cerebral protection to reduce the period during which the brain is not perfused [8, 9, 10, 11, 12, 13].

Despite the growing research and clinical experience, there is still only scarce evidence for neuroprotective strategies yet. The most recent ACCF and EACTS guidelines recommend (class II) deep HCA and selective anterograde cerebral perfusion (SACP) as reasonable strategy while emphasizing the importance of institutional experience in selecting the most appropriate technique [14, 15].

2. Cerebral perfusion and autoregulation

The main goal of cerebral protection, whatever the technique is used, is to preserve the most physiological characteristics of cerebral function. In the adult, the brain weighs around 1400 g; this means 2–3% of the total body weight. In contrast, the mean cerebral flow is about 750 ml/min which represents about 15–16% of the total cardiac output. This relationship demonstrates the huge metabolic demand of the brain and the importance of preserving its metabolic activity. Along the cerebral circulation, there is a constant drop in intravascular pressure, with a mean pressure of 80 mmHg in the common carotid arteries, 60 mmHg in the intracranial carotid artery, and 20mmHg in the middle cerebral arteries. It is around 15 mmHg in the cortical veins and 5–7 mmHg in the longitudinal sinus.

Autoregulation of the cerebral blood flow plays a major role in preserving the integrity of the cerebral metabolism; in general, autoregulation is maintained for a spectrum mean arterial pressure values between 50 and 150 mmHg [16, 17, 18]. This means that there is no linear not exponential relationship between cerebral blood flow and the mean arterial pressure within these values. However, regulation of cerebral blood flow varies according to the central temperature, with a more or less constant reduction of flow of 7% for each degree Celsius of hypothermia. Cerebral autoregulation nearly disappears when the brain temperature is below 15°C [19]. Cerebral oxygen consumption is approximatively 2.9 ml/min/g at 37°C and reduced to 0.90 ml/min/g at 25°C while at 20°C, it is only 20% of its physiological value. At 8°C, metabolic status is still 10% of the normal value [20].

Any sudden interruption or major reduction of the cerebral blood flow occurring at normothermia results in a dramatic drop of the oxygen and glucose supply which results in a loss of active phosphorylation of the cells and rapidly empties the adenosine triphosphate (ATP) reserves indispensable to normal brain activity. The intracellular pH rapidly collapses, while the transmembrane exchanges are interrupted. The electrical polarity is rapidly reduced, and potassium gets out of the cells. At the same time, the calcium and natrium channels open widely and lead to a massive flow of both calcium and natrium into the intracellular space. Together with the ongoing tissue acidosis, several enzymes are activated and will accelerate degradation of proteins, while peroxynitrite acidotic radicals and endonucleases induce DNA fragmentation. Altogether, these biochemical processes rapidly lead to cellular death. This process of neuronal necrosis may be considerably increased in case of blood flow restoration and ends in additional reperfusion injuries.

Cooling and rewarming processes are also of major importance to avoid additional injury due to inhomogeneous temperatures within the brain. The relationship between cerebral blood flow and metabolism may be analyzed using transcranial Doppler sonography which is able to demonstrate peak flow velocity depending on the respective actual cranial temperature. At normothermia and mild hypothermia, the maintenance of coupling means that blood flow velocity and temperature remain in a linear relationship. However, when deep hypothermia is targeted, autoregulation will be lost. Cerebral blood flow becomes pressure-dependent [21]. In case of rapid cooling under the condition of alpha-stat acid–base management, transcranial Doppler ultrasound will demonstrate a significant drop of flow velocity. This may end in inhomogeneous thermal distribution which means that brain structures located deeper in the skull are less efficiently cooled than those located at the surface [22].

In the past, pH-stat acid–base management and slow cooling have been considered as the best strategy to obtain the most uniform cooling of the brain together with the maintenance of the most optimal perfusion [23]. Hypothermia-related disruption of the normal relationship between cerebral blood flow and metabolism is even more important during rewarming. Greeley described a phenomenon where a transient disruption of cerebral vascular reactivity occurs during rewarming following a period of deep hypothermia [24]. As a consequence, flow (and therefore also velocity) remains at a lower level, while the metabolic demand of the brain increases together with the brain temperature. Greeley used the wording ‘cerebral vasoplegia’ to describe the loss of the relationship between flow (velocity) and metabolism. This uncoupling may result in relative hypoperfusion and, more dramatically, in ischemic brain injury.

3. Physiology of hypothermic circulatory arrest

The metabolism of the brain is generated by adenosine triphosphate that is produced during aerobic glycolysis. The metabolic rate of the cerebral tissue is seven times higher than that of the body. Anaerobic glycolysis, unlike in liver or muscle, cannot sustain the required energy demands of the brain. Therefore, a short anaerobic period with consecutive rise in lactate concentration will rapidly be deleterious for the cerebral cells.

Since the brain does not have glucose reserves, a constant supply through a continuous blood flow is mandatory, although changes in metabolic demands can be met by appropriate changes of blood blow upon a certain limit (cerebral autoregulation).

Experimental and clinical research has demonstrated that cerebral blood flow autoregulation can be affected by patient’s factors such as age, diabetes, and arterial hypertension but also by conditions associated with specific changes during such surgical procedures (anesthesiologic management, pressure changes during extracorporeal perfusion, hemodilution, loss of pulsatility, as well as hypothermia). Depending on how reduction of cerebral flow occurs, two different types of perioperative cerebral injury may happen during aortic and/or cardiac procedures. The most devastating one is the classical stroke which is caused by localized cerebral ischemia (through embolization of corpuscular or gaseous particles). The other type of injury may be the result of global ischemia and is related to interrupted or temporarily inadequate perfusion [25]. In contrary to the frank stroke that is usually easily detectable through CT-scan and MR-imaging, temporary neurological dysfunction is a much more subtle form of global ischemia that manifest clinically under various symptoms (disorientation, delirium, amnesia, restlessness, and others).

Since it is not possible to completely turn off the energy demands of the brain while maintaining cellular viability, the strategy of cerebral protection includes methods to prevent cerebral anoxia and acidosis during interruption of the cerebral blood flow or to provide some cerebral perfusion during a planned period of circulatory arrest while limiting its duration to a strict minimum.

Nevertheless, hypothermia (even at different temperature levels) remains the principal method of brain protection while additional strategies were developed later as a solution to avoid a “complete” circulatory arrest or to make the arrest safer (e.g., extending its duration without additional risks). Independently of these developments, the basic questions about circulatory arrest, namely how cold and how long is safe, remain crucial.

According to numerous experimental and clinical studies, a circulatory arrest period is considered to be safe for up to 30 minutes at 15°C and 40 minutes at 10°C [8, 10, 26, 27]. In the pediatric literature, there are sufficient data that hypothermic arrest over 40 minutes is associated with significantly poorer neuro-developmental outcomes. In adults, a decline in neurocognitive performance has been observed when the duration of arrest exceeds 25minutes in the absence of additional neuroprotective strategies.

3.1 Levels of hypothermia

With increasing surgical experience and rising numbers of procedures on the aortic arch, the concept of hypothermia has considerably developed. When referring to “hypothermia”, some precisions may be necessary, namely the real level of temperature as well as the location where the temperature is assessed. Several papers have tried to define the different levels of hypothermia—they are summarized in Table 1 [15, 29, 30]. These classifications differentiate between deep, moderate, and mild hypothermia and based on the belief that the reduction of the suppression of brain metabolism is the main determinant of a successful arrest temperature. Nasopharyngeal (alternatively esophageal) temperature was selected as the reference because it closely corresponds to the brain temperature during cooling and rewarming. However, no publication has studied in detail whether the spinal cord and the abdominal organs are sufficiently protected with moderate hypothermia, especially during prolonged HCA duration.

Profound	< 14°C
Deep	14–20°C	< 20°C		< 20°C
			20–24°C		Moderate low
Moderate	20–28°C		20–25°C
				24–28°C	Moderate high
Mild	> 28°C	> 25 °C		> 28°C
	[28]	[29]		[15]

Table 1.

Different classifications of hypothermia.

Whether or not repair of type A aortic dissection with either an open distal anastomosis at the level of the proximal arch or with total arch replacement can be performed under moderate hypothermia in patients receiving SACP is still a matter of actual clinical research. To be accepted and generalized into regular surgical practice, the resulting stroke and mortality rates should probably be less than 5–10%, respectively and 10–15% in the acute setting.

3.2 Deep hypothermic circulatory arrest (DHCA)

Lowering the temperature of the whole organism to 18°C has been considered in the past as a safe technique for complex aortic arch procedures, especially in dissection patients because of the uncertainty concerning the expected duration of circulatory arrest to safely perform the distal anastomosis will be performed.

To improve the safety of DHCA, additional points have been worked out to avoid gradients of temperature between different areas and organs as well as within the brain itself; smooth cooling and rewarming process and assessment of both the rectal (or urinary bladder) and nasopharyngeal temperatures while packing the patient’s head in ice should help to maintain the most homogeneous level of cerebral hypothermia during the arrest duration.

DHCA is rather simple that does not require any special equipment other than the regular circuit with a high-performance heat exchanger. Its benefits include a bloodless field and no need for any cannula or additional aortic manipulation. However, it may be associated with some drawbacks. DHCA requires a long time to lower the patient’s temperature to the targeted level and to rewarm as well, with all side-effects on the coagulation and inflammatory systems. The absence of clear criteria that indicate that circulatory arrest is safe—some consider that CPB can be discontinued as soon as the temperature reaches 18 or 20°C while others consider that the circulatory arrest can be initiated only when the electroencephalography (EEG) is completely flat or when oxygen saturation of the venous return in the jugular vein is higher than 95%.

The maximal duration of DHCA without neurological dysfunction remains unclear but the upper safe limit at 12–20°C is considered to be 25–30 minutes [31]. The risk of neurologic disturbance raises significantly when DHCA exceeds 40 minutes and the risk of mortality when it is over 65 minutes. DHCA without any additional protective adjuncts has been progressively abandoned by most groups in favor of more moderate hypothermia active cerebral perfusion methods. A meta-analysis by Manoly et al. with nearly 6000 patients showed significantly lower mortality and incidence of stroke with moderate hypothermia with SACP compared to deep hypothermia alone [32].

4. Institutional cannulation and perfusion technique

Different sites of cannulation (ascending aorta, iliac/femoral, or subclavian/axillary) have been used and successfully described as potential approaches for the arterial return of CPB during repair of acute type A aortic dissection. All of them have advantages and disadvantages that have been extensively described in the literature. Therefore, I would like to focus on the technique we adopted more than 25years ago at the University Hospital in Bern, Switzerland and I would like to summarize the main principles in the following lines.

Although surgical preparation and access to the right subclavian artery need more time than exposure of the femoral artery, several publications have demonstrated excellent outcomes compared to the historical series in which arterial return was performed via femoral cannulation. Subclavian artery cannulation may attenuate the possibility of brain malperfusion which can occur at the beginning of CPB in case of pressurization of the false aortic channel, or when a cross-clamp is placed on the ascending aorta. Personally, I am not in favor of a routine direct aortic cannulation strategy, however, in case of any unexpected technical difficulty, I would accept it for rapid institution of CPB. Two additional smaller roller pumps are used, one for instillation of cardioplegia, the other, placed beyond the oxygenator for cerebral perfusion. Continuous running through a recirculation tubing is recommended during the period of systemic circulatory arrest.

Our strategy has been to avoid cross-clamping the aorta because this maneuver may lead to additional injuries of the already dissected aorta and the supra-aortic branches. This means that the procedure usually starts with distal repair once the target temperature has been reached and that proximal repair is performed during rewarming. This sequence has the additional advantage of shortening the time period the patient is kept cool. The logic for this approach has become evident at our institution with a yearly number of 50–60 type A aortic dissections.

Once the targeted temperature of 26–28°C has been obtained, CPB is interrupted, and the aortic arch is opened. Two flexible thin perfusion catheters (Le Maître, Burlington, MA, USA) are introduced in both common carotid arteries, and SACP is started with a flow between 10 and 15 ml/kg/min (total usually 500–800 ml/min) with a temperature of the perfusate between 22 and 24°C and a pressure around 50–70 mmHg. The balloons of these perfusion catheters are inflated smoothly once perfusion has started to de-air the supra-aortic branches. Another very important feature in patients with type A aortic dissection is to cannulate the true lumen after it has been clearly distinguished from the false lumen by visual inspection from within the aortic arch. Following cannulation, the balloons are gently inflated until backward pulling cannot displace the catheters (Figures 1–3).

Figure 1.

Schematic drawing of unilateral antegrade cerebral perfusion through the right subclavian artery with clamping of the supra-aortic branches. (Reproduced with permission from Ref. [33]).

Figure 2.

Schematic drawing of bilateral antegrade cerebral perfusion through both common carotid artery with endovascular occlusion of the left subclavian artery using a Fogarty. (Reproduced with permission from Ref. [33]).

Figure 3.

Thin LeMaitre Vascular© perfusion catheter for selective antegrade cerebral perfusion with an inflatable balloon to block the backflow. (Reproduced with permission from Ref. [33]).

In the majority of cases, the left subclavian artery is occluded with a small Fogarty catheter from inside the vessel, except when the right vertebral artery is occluded. The right radial artery pressure as well as the pressure at the tip of both carotid catheters is maintained at 50 mm Hg.

To ensure true luminal perfusion after confection of the distal anastomosis and to minimize false luminal pressurization at all, reperfusion is started in an orthograde way via the side-arm graft of a Vascutek Anteflo prosthesis. During rewarming, proximal repair is performed while decannulation and reconstruction of the right subclavian artery can be performed safely.

5. Review of cerebral perfusion

The most optimal type of cerebral perfusion in the setting of acute type A aortic dissection repair remains a matter of preference/debate while different opinions are reported in the literature. Basically, there are several options:

• Unilateral antegrade cerebral perfusion via the right subclavian artery as it is cannulated for the arterial return of the CPB circuit,

• Bilateral SACP with two or three perfusion catheters introduced in the innominate artery (and pushed further into the right common carotid artery), the left common carotid artery, and eventually into the left subclavian artery,

• Retrograde cerebral perfusion (RCP) via the superior vena cava.

5.1 Antegrade cerebral perfusion (ACP)

The technique consists of perfusing one or several supra-aortic vessels with oxygenated blood in a physiological way at a flow and pressure compatible with the maintenance of a proper metabolic supply, providing equal distribution of the perfusate to both cerebral hemispheres while maintaining the core temperature at a moderate level. From the historical perspective, there are two different methods of ACP that differ regarding the temperature of the perfusate, the complexity of the CPB circuit, and the mode of cannulation of the supra-aortic branches.

The French technique uses perfusion with cold blood at a temperature of 10–12°C while the patient’s core temperature is maintained at 25–28°C. The intention is to provide a homogeneous distribution of the cold perfusate to both hemispheres with significant reduction of the metabolic demand, although the cerebral blood flow regulation is not preserved. A regular circuit is modified through the addition of a heat exchanger beyond the oxygenator. The flow rate is maintained at 7–10 ml/min/kg, a pressure between 60 and 70 mmHg. No adjuncts are used to enhance cerebral protection [5].

The Japanese technique perfuses the brain and the body at the same temperature level. For this purpose, the CPB equipment is somewhat modified, with an additional arterial line that originates from the main arterial perfusion line. A separate pump is dedicated to brain perfusion. This technique has the advantage that a single heat exchanger is used because both, the CPB and the cerebral perfusion are performed at the same temperature. A total flow of 10 ml/kg is given through both cannulas. Because of its simplicity and the easy cannulation of the cerebral vessels, this technique of SACP has gained large acceptance [6].

Antegrade cerebral perfusion presents several advantages compared to hypothermic arrest alone or in combination with retrograde cerebral perfusion. It provides the most physiological type of perfusion - mimicking the normal blood flow to the brain, and obviates the need for deep hypothermia, thereby reducing the required time for cooling and rewarming and the risk of complications associated with a prolonged pump run like coagulopathy and pulmonary dysfunction. The suggested risks and drawbacks of antegrade perfusion include the risk of embolization of particles and air into the cerebral vessels during the introduction of the perfusion catheters, malperfusion through kinking of the catheters or false positioning, and finally the somewhat cumbersome procedure with additional manipulations of the supra-aortic branches. Nevertheless, these potential drawbacks can be rapidly eliminated with growing experience. Once the catheters have been introduced in the corresponding supra-aortic branches, they can be gently retracted to the head of the patient and do not obscure the view in the operative field.

5.1.1 Uni- or bilateral antegrade cerebral perfusion?

The rationale for one-, two-, or even three-vessel perfusion represents a matter of discussion. The debate was initiated following the publication of two clinical studies in which only unilateral perfusion from the right subclavian artery was used with excellent results regarding postoperative neurologic disorders [34, 35]. For this reason, unilateral perfusion technique has been adopted broadly in the clinical practice. In some studies, a decreased rate of permanent neurologic deficit following unilateral perfusion was observed, but not in the rate of transient neurologic disorders. Those in favor of unilateral perfusion concluded that the technique offers at least similar protection of the brain and the abdominal organs than bilateral SACP and that it may reduce the incidence of embolism arising from surgical manipulation on the supra-aortic branches [36].

However, equality of cerebral protection through unilateral or bilateral perfusion assumes that the circle of Willis provides enough blood flow on the contralateral brain hemisphere. Clinical studies have demonstrated that completeness of the circle can be expected in approximately 60% of patients. During unilateral cerebral perfusion, the flow velocity in the contralateral middle cerebral artery varies considerably, but the flow itself never disappears. From these observations, one can conclude that the anatomical particularities of the circle of Willis—with a broad range of variations—do not automatically correlate with its functional achievements when examined intraoperatively [37, 38, 39]. Meanwhile, both types of cerebral perfusion are largely accepted by the surgical community but it seems that bilateral SACP may be safer in case the circulatory arrest time is over 40 min [40, 41, 42, 43]. In practice, the decision to use unilateral or bilateral perfusion is largely dependent on the institutional preference and experience, and the expected duration of the circulatory arrest plays a major role as well.

5.1.2 Clamping, snaring, or occlusion of supra-aortic branches with balloon catheters?

I personally consider the handling of the supra-aortic branches in the setting of a weakened arterial wall as it is the case in aortic dissection to be crucial [33]. For this purpose, we have used intraluminal occlusion with customized small and very smooth perfusion catheters with balloon occlusion (Figure 1). I see three potential advantages:

• Neither clamping nor snaring of any of the supra-aortic vessels is necessary. This is probably more important than generally considered, especially in the setting of a fragilized vessel wall through acute dissection. In this situation, there is an additional risk for a manipulative injury because of the dissection and this may cause obstruction or even complete occlusion is high.

• The introduction of a perfusion catheter into the true channel of the vessel with subsequent inflation of the balloon may favor the expansion of the dissected layers from inside and bring the dissected layers together, especially when they have been treated with biological glue.

• An additional benefit of balloon inflation may be the avoidance of downstream embolization of biological adhesive to glue the dissected layers of the vascular wall [44].

I had the privilege to recently work at another institution, where a strategy of unilateral ACP through the right subclavian artery was used routinely in patients operated on because of type A aortic dissection. All patients received an open distal anastomosis during which the innominate artery was clamped. In a consecutive series of 55 patients, I observed five cases of postoperative occlusion of the innominate artery, most probably due to a clamp injury. In four patients, the dissection process already involved the innominate artery on a preoperative CT scan. Postoperatively ipsilateral stroke was observed in all patients, in one patient it was associated with a lethal outcome. One patient underwent surgical revascularization with an interposition graft between the ascending aorta and the innominate artery and the other was treated with an endovascular stent of the innominate artery [33].

5.1.3 Should the left subclavian artery be perfused?

In the majority of reports of SACP, only the right subclavian and the left common carotid arteries have been perfused. No clinical consequences seem to be related to absence of left subclavian artery perfusion. Nevertheless, some groups, particularly in Japan perfuse systematically the left subclavian artery, especially in case the preoperative investigations have demonstrated occlusion of the right vertebral artery or a dominant/single left vertebral artery. In case of acute dissection without preoperative information, no or very weak backflow through the left subclavian artery may be considered as an indication to perfuse it antegradely. Independently of the previous considerations, it has been well demonstrated that the left subclavian artery may play an important role for the spinal cord perfusion through the anterior spinal artery [45, 46]. If the left subclavian artery is not selectively perfused, it may be important to occlude it to avoid steal syndrome and consecutive ischemia of the posterior cerebrum.

5.2 Retrograde perfusion

Retrograde cerebral perfusion has been first described by Mills and Ochsner in 1980 for another indication than aortic arch surgery, namely massive air embolism during CPB to flush out the arterial cerebral circulation on a retrograde way [47]. This technique was then described by Ueda as an adjunct to hypothermia during repair of aortic arch pathologies and is based on the idea that the brain could be perfused retrogradely through the venous and capillary systems on the analogy of retrograde cardioplegia [48]. The technique for retrograde cerebral perfusion may vary from institution to institution but the basics are similar; it includes a standard bi-caval cannulation with caval snaring. A simple modification to the normal CPB circuit is required with an additional connection between the arterial line and the superior vena cava line. This “shunt” remains closed during perfusion throughout CPB and once the targeted temperature is reached, the circulation is arrested. The arterial cannula is occluded, and the circuit is drained into the venous reservoir. The superior vena cava is snared at the entrance to the right atrium and the connection to the arterial line unclamped. Blood is then perfused retrogradely via the superior vena cava and returns to the opened aortic arch via the arterial system; this can be easily seen in the operative field when dark venous blood comes out of the supra-aortic branches (wash out of ischemic metabolites?) [49, 50, 51]. The latter can be returned into the circuit through cardiotomy suction. The perfusion pressure is kept around 20–25mmHg.

Among the most important potential benefits of RCP are maintaining cerebral hypothermia and flushing out atherosclerotic or gaseous emboli. However, this may not be the major problem in aortic dissection. On the other side, RCP may cause cerebral edema due to high venous flow rates and perfusion pressure.

Currently, there are no prospective randomized studies that show RCP has an advantage over HCA alone. Hagl analyzed the risk factors for stroke in a large collective of 700 patients [52]. RCP had no beneficial effects on outcome, but antegrade perfusion led to a decrease of temporary neurological events. Similar results were found by Okita who compared RCP to SACP in a prospective study [53]. Bonser has demonstrated that retrograde cerebral perfusion is unable to attenuate the metabolic changes induced in the brain by deep hypothermia [54].

From the current scientific evidence, it is actually not justified to support a strategy in favor of RCP. However, it is not excluded that RCP may somehow contribute to homogeneous cooling to the brain, and thereby makes prolonged duration of circulatory arrest safer than HCA alone.

6. Drugs

Several drugs have been used in the past and some of them are still administered today but the evidence to support this strategy is scarce. The most common substances used are lidocaine, thiopental and steroids, even though the mechanisms of protection are not fully elucidated. There is some evidence suggested that prophylactic use of dexmedetomidine for postoperative sedation reduced the rate and duration of postoperative delirium [55].

Diuretics like mannitol and furosemide are also interesting substances for adjuvant pharmacological protection during HCA—they work mainly through a reduction of cerebral edema [56]. Mannitol, besides reducing cerebral edema and intracranial pressure, has an important effect as a free radical scavenger and is administered both during the cooling and rewarming period. In Bern, our anesthesiologists have supported the use barbiturates 20years ago, but we have abandoned their use mainly because a net benefit could not be demonstrated so far. The results without barbiturates but instead with moderate hypothermia and SACP were even better. In addition, the potential myocardial depressant effect can be avoided. Others continue to incorporate high-dose thiopental in their protective regimen [57].

7. Intraoperative monitoring

Despite significant improvements in field of cardiovascular surgery (anesthesia, intensive care medicine, perfusion technology, and surgical technique itself), cerebral damage remains a fastidious complication of aortic dissection repair irrespective of the technique used for brain protection. Ideally, intraoperative monitoring should help to detect any global hypo- and hyperperfusion, significant regional perfusion deficits, and sudden changes in the perfusion characteristics. Nevertheless, there is no evidence so far that intraoperative monitoring reduces the risk of neurological injury. In the following, I will briefly review methods of intraoperative monitoring.

Classical electroencephalography (EEG) provides information on the whole cortical and subcortical structures in real time. EEG becomes totally flat when the cerebral temperature reaches a level below 20°C. Unfortunately, EEG does not give any information on deeper cerebral structures. The bi-spectral index (BIS) is a simpler surrogate of EEG. It provides reliable monitoring and is quite simple to use in any circumstance [58, 59].

Bilateral transcranial Doppler allows assessment of a symmetrical flow in the middle cerebral artery and detection of embolic phenomena but is limited to the anterior cerebral circulation [60]. Similarly to EEG, it requires a specialized technician in the operating theater. Transcranial Doppler is the only method to continuously assess changes in cerebral hemodynamics during CPB. It may be of particular interest during repair of acute ascending aortic dissection, for instance in case of malperfusion of the carotid arteries. This potentially catastrophic condition may be immediately recognized when sudden loss of Doppler signal may signify severe cerebral ischemia.

Serial determination of jugular venous bulb oxygen saturation allows continuous assessment of cerebral metabolism and may be used to detect intraoperative cerebral ischemia [61]. The method is easy to implement. A central venous catheter is used to cannulate the jugular bulb. Two punctures and two guidewires are necessary—the first is directed cephalad and the second is directed into the central circulation. A pulmonary artery catheter is placed in a standard fashion and the jugular bulb catheter is then advanced towards the jugular bulb using the Seldinger technique.

Near-infrared spectroscopy (NIRS)—also known as transcranial cerebral oximetry—is probably the most popular method of cerebral monitoring [62]. It is simple, noninvasive, and highly reproducible. It assesses regional cerebral oxygen saturation within the brain through the skull by absorption of infrared beams and may allow detection of cerebral hypoperfusion. It requires two or three adhesive electrodes to be placed on the forehead of the patient. The oxygen saturation of the underlying cortical structures appears directly on the monitor screen. A decrease in the regional saturation to values inferior to 60% of the baseline is a sign of severely altered brain perfusion, while a drop to 55% or less for of duration of 5 min means a high probability of a permanent neurologic lesion. Similarly to EEG, NIRS does not allow assessment of posterior and deeper structures of the brain.

A very simple method of monitoring is the recording of bilateral radial artery pressure that may give useful information about the perfusion pressure in the contralateral subclavian artery. Pressure should be maintained between 50 and 80 mmHg throughout the procedure.

In summary, monitoring of the brain function should be performed at least using BIS and regional NIRS of forehead even though there is few randomized evidence to support one technique over the other. A multimodal monitoring strategy may increase the sensitivity of detecting cerebral ischemia.

8. Clinical experience with cerebral protection in Europe: the result of a single survey

Because a definitive consensus has not yet been reached and many different approaches regarding site of cannulation, core and perfusate temperature, flow, monitoring methods as well as visceral protection, a survey was sent to 450 cardiac surgery units across Europe to evaluate the methods used for cerebral protection during aortic arch surgery and answered by 141 centers [63]. In the following, I will summarize the answers concerning the current handling of acute aortic dissection.

The right subclavian/axillary was the favorite site for arterial cannulation. Bilateral SACP was the most frequent method of brain protection in acute presentation. Unilateral perfusion was used in approximately 1/3 of the cases, while deep HCA and RCP are very rarely used in Europe and almost exclusively in patients with acute dissection.

In acute cases, 2/3 of centers perform distal anastomosis at a core temperature between 22 and 26°C, while 1/3 still use deeper temperature (down to 15°C in occasional cases). Only a few cardiac units use temperatures around 30–32°C. Flow and pressure of the are fairly similar among all centers (10–15 ml/kg), respectively around 60 mmHg, while average temperature of the perfusate is 22°C. At that time, barbiturates were used in 60% of centers, however, with a decreasing tendency since then.

The survey shows that the majority of the participating centers proceed within reasonable ranges published in the literature. Unilateral perfusion is still a broadly accepted method; however, if circulatory arrest duration is expected to be over 30–40 min, a bilateral SACP is preferred. Cerebral monitoring is part of the routine intraoperative strategy while NIRS associated with bilateral monitoring of perfusion pressure seems to be the preferred method of a majority of institutions. Hypothermia is always used, while circulatory arrest at warmer temperatures is being adopted more frequently.

9. Conclusion

Brain protection has been a major issue since the early period of aortic arch surgery [32, 64, 65, 66, 67, 68, 69]. With improvements in surgical techniques, operative technology, and methods of blood management, the risk of stroke following repair of type A aortic dissection can be reduced to less than 5–10%, also with a mortality risk of less than 10%. This corresponds to the actual standard to which any innovation in the field of aortic dissection repair must be compared, including less invasive endovascular procedures.

Conflict of interest

“The authors declare no conflict of interest.”