In complex aortic reconstructions requiring prolonged periods (>40 minutes) of circulatory arrest, DHCA alone may not provide adequate cerebral protection. In these situations, adjunct methodologies to DHCA, such as selective antegrade cerebral perfusion and retrograde cerebral perfusion, have been employed and have gained widespread adoption.
Selective Antegrade Cerebral Perfusion
Kazui et al. described the first use of selective antegrade cerebral perfusion in which perfusion was administered through both the innominate and left common carotid arteries.25 Since that time, selective antegrade cerebral perfusion has gained widespread popularity as a modality to provide optimal cerebral protection during complex ascending and transverse aortic reconstructions. Antegrade perfusion of the brain during DHCA is typically administered through a cannula inserted in the right axillary artery (Fig. 14-2). The axillary artery has become the artery of choice caused by its size, accessibility, and resistance to atherosclerotic disease burden. The right axillary artery is generally approached through an infraclavicular or deltopectoral groove incision. A 6-, 8-, or 10-mm Dacron graft is anastomosed in an end-to-side fashion to provide adequate flow and to ensure adequate perfusion of the right upper extremity. Direct cannulation of the axillary artery is avoided caused by the risk of inducing trauma, which may lead to dissection. The innominate artery is subsequently isolated proximal to takeoff of the right subclavian artery and perfusate temperature is usually set at 18°C with a flow between 10 and 20 mL/kg per minute and adjusted to maintain a pressure of between 40 and 50 mm Hg in the right radial artery.
Schematic of right axillary artery cannulation for antegrade cerebral perfusion (ACP). Insert shows open aortic arch and ACP with occlusion of arch vessels to ensure perfusion of Circle of Willis.
The need to cannulate relatively small and often diseased arch arteries and the presence of additional cannulas in the operating field constitute the main drawbacks of the technique. Direct cannulation of the common carotid or axillary arteries can result in dissection of the arterial wall and embolism of atheromatous plaque material or air. Furthermore, arterial flow depends on proper positioning of the cannula tip within the vessel. For these reasons, some surgeons rely on a unilateral perfusion of the brain with sole cannulation and perfusion of the right subclavian artery. In these situations, the right vertebral and right common carotid artery territories are perfused in an antegrade fashion. The blood reaches the left cerebral hemisphere through the circle of Willis and, to a lesser extent, through cervicofacial connections. Therefore, it is important that the take-offs of the left common carotid and left subclavian arteries be occluded to avoid a steal of blood down these arteries. Occlusion (usually with an inflatable balloon) of the descending aorta is also a useful maneuver to improve overall body perfusion. Effective somatic perfusion (including the abdominal organs, spinal cord, and lower limb musculature) has been documented with this maneuver.26 The presence of an aberrant right subclavian artery (arteria lusoria) is a clear contraindication to the use of this perfusion method. The aberrant origin of the artery usually is identified readily by computed tomographic scanning or magnetic resonance imaging. The burst of blood from the descending aorta during opening of the aortic arch should alert the surgeon to this anatomical variation and prompt a direct cannulation of the ostium of the right and left common carotid arteries.
Sequential perfusion of the cerebral arteries provides additional safety to unilateral cerebral perfusion and avoids cannulation of small or diseased arch arteries.27 The right subclavian artery remains perfused during the whole procedure. A vascular graft is sewn immediately to a common patch of aortic wall including all the arch vessels,28 or the second branch of a multiple-arm prosthesis is anastomosed to the left common carotid artery. Perfusion then is instituted through this additional graft and enhances cerebral perfusion.
Retrograde Cerebral Perfusion
Retrograde cerebral perfusion (RCP) is performed by isolation and perfusion through the superior vena cava shortly after the interruption of antegrade arterial flow. The superior vena cava (SVC) is typically snared below the azygous vein to provide retrograde cerebral blood flow and blood flow to the anterior spinal plexus and, to a small degree, the remainder of the visceral organs (Fig. 14-3). Alternatively, the SVC is directly cannulated for bypass, the cannula snared, and arterial flow directed into the SVC from the cardiopulmonary bypass circuit after clamping the IVC cannula. Pressurization of the venous system to 20 to 25mm Hg allows for blood flow into the upper extremities, jugular veins, and spinal channels, eventually crossing the capillary bed into the arterial system and finally draining into the open aortic arch. The proposed benefits of RCP are to maintain cerebral hypothermia, flush out embolic debris and air, provide metabolic support, and allow for the removal of toxic metabolites and waste products.29
Schematic of retrograde cerebral perfusion (RCP). Arterial blood is perfused via the superior vena cava, with a target CVP of 25 mm Hg. Flow can be monitored through the open aortic arch. Balloon occlusion catheter can be employed to increase perfusion to body.
The initial report that described the use of RCP to assist in brain protection during circulatory arrest created considerable controversy.30 Investigators questioned whether perfusion of the brain via the cerebral venous system offered any metabolic delivery to the brain, whereas others felt that high venous cerebral pressure may cause edema. Based on the subsequent results of clinical and experimental studies, it is now generally accepted that RCP produces deep and homogeneous cooling of the brain hemispheres and the expulsion of solid particles or gaseous bubbles from the arch arteries.31 Although there is generally excellent backflow with RCP and an open aortic arch, occlusion of the inferior vena cava to decrease the pressure gradient between the two venous territories effectively reduces the amount of stolen blood.32 Interstitial edema is a rare but potential complication of retrograde perfusion and can lead to cerebral edema and hypertension when the perfusion pressure is set above 25 mm Hg.33
Because RCP is nonphysiologic, it is critical that the conduct of administering RCP is performed correctly. For venous-to-arterial blood flow to occur, the aortic arch must be wide open during RCP, thereby minimizing the pressure gradient between the venous and arterial vasculature. Any arterial occlusion, including severe atherosclerotic cerebrovascular disease, may impede cerebral perfusion, and may result in cerebral edema in cases of high venous pressure. Furthermore, contrary to common practice, patients should only be partially exsanguinated at the onset of circulatory arrest to assure that full venous capacitance is obtained. RCP in these situations is most likely to contribute to optimal retrograde cerebral blood flow and exceptional results when performed correctly.34
Rewarming represents a critical time period during which any additional harm to neurons might induce permanent injury or death. Providing a favorable hematologic environment, ensuring optimal hemodynamic conditions, and avoiding cerebral hyperactivity should provide optimal conditions for recovery of the energy-depleted brain.14 It is crucial to begin reperfusion slowly after circulatory arrest. An initial period of “cold blood low-pressure reperfusion” washes out accumulated metabolites, buffers free radicals, and provides substrates for regeneration of high-energy molecules before the resumption of cerebral electrical activity. Furthermore, an adequate hematocrit during this reperfusion period is attractive not only because of its oxygen-carrying4 capacity, but also because of its buffer, redox, and free-radical scavenging capacity. Glycemia should be monitored closely and treated aggressively, because hyperglycemia, which is stimulated by the release of endogenous catecholamines, increases intracellular acidosis and can prevent or delay the restitution of metabolic homeostasis.35 During rewarming, cerebral vascular resistance and energetic metabolism are impaired in proportion to the severity of ischemia.36 Cerebral perfusion is reduced and glucose is derived in part from the less efficient anaerobic pathway, with oxygen coupling during oxidative phosphorylation being partially interrupted.37 This vulnerable period can last for 6 to 8 hours after initiation of reperfusion.21 During this time, an abnormally high extraction of oxygen and glucose is necessary to sustain the cerebral metabolic rate.38 Jugular venous oxygen saturation is often below 40% during this recovery period and cerebral autoregulation may not compensate for reduction in oxygen delivery, which could occur with postoperative events such as acute hypotension, hypoxemia, and anemia.
The temperature of the perfusate during the rewarming phase should be managed carefully. Detection of increased cerebral activity should prompt immediate therapeutic action, which includes deep anesthesia, appropriate sedation, and reduction of temperature. Monitoring cerebral electrical activity during the rewarming phase (and thereafter if circulatory arrest has exceeded the safe ischemic period or if signs of abnormal electrical activity are present) could help to limit the extent of secondary damage to the brain. The perfusate temperature should not exceed 37°C because a relative hypothermia may prove to be beneficial for optimal brain recovery. It is our practice to maintain perfusate temperature at 37°C for a period of at least 20 minutes when a patient has achieved normothermia to minimize a downward hypothermic trend. Electrical hyperactivity of the brain can trigger overwhelmingly destructive reactions. The disorder is not uncommon after prolonged circulatory arrest and actually is considered a sign of ischemic injury.39
Outcomes after DHCA, RCP, and SACP
Clinical neurologic deficits after DHCA encompass a variety of disorders ranging from deep coma to subtle, barely perceptible alterations in cognitive functions, to focal deficiencies and behavioral changes. In the immediate postoperative period, the return of sophisticated neurologic function is often obscured by the administration of sedative and analgesic agents. A focal deficit is caused by interruption of blood in a terminal vascular territory, usually secondary to embolism, and is often the consequence of atheromatous burden. The clinical expression, typically, is a motor-sensory deficit, aphasia, or cortical blindness. Computed tomographic scanning and magnetic resonance imaging are able to detect a sharply demarcated area of necrosis in the cerebral cortex. The prevalence of a focal deficit in clinical series ranges from 5 to 10% after elective aortic surgery with the use of deep hypothermic circulatory arrest. Age, atherosclerosis, and manipulation of aorta are more potent risk factors than the duration of circulatory arrest.24 Retrograde perfusion of the aorta during cardiopulmonary bypass (with the arterial cannula inserted into the femoral or iliac artery) also has been associated with an increased risk of focal deficit because retrograde flow can dislodge floating atheromatous plaques and thrombi loosely attached to the walls of thoracic aortic aneurysms.40
Diffuse neurologic deficits are caused by global cerebral ischemia that produces various levels of cellular dysfunction. In its mildest forms, the neurons are viable but temporarily unable to function properly. The clinical spectrum of neuropsychological disorders ranges from benign and reversible conditions such as transient confusion, stupor, delirium, and agitation to more serious and debilitating conditions such as seizures, parkinsonism, and coma. Imaging studies are often normal, although in the most severe forms, scattered areas of necrosis may appear. The wide range of incidences (from 3 to 30%) of diffuse deficits after circulatory arrest quoted in the literature reflects the subtle and often unrecognized nature of most deficits. Scrupulous postoperative evaluation of neurologic function discloses a frequency of between 10 and 20%.41,42 Age, conduct of cardiopulmonary bypass, and prolonged duration of circulatory arrest are recognized risk factors for the occurrence of diffuse deficits. Disorders that impair vascular reactivity and cerebral autoregulation, such as diabetes and hypertension, have also been associated with an increased incidence of diffuse deficits.43
With refinement in neurologic evaluation, including behavioral and cognitive testing, it appears that subtle deficits occur in a much larger proportion of patients after relatively short ischemic times. Transient neurologic dysfunction, a condition once not considered a deficit, and postoperative electroencephalographic hyperactivity appear now as definitive markers of long-lasting cerebral injury.33,41 One-fourth of patients with transient deficits perform poorly on postoperative neuropsychological testing, and the deficit, affecting mainly memory and fine motor function, persists in many of them after hospital discharge. The risk of transient neurologic deficit starts when deep hypothermic circulatory arrest exceeds 25 minutes.24 The risk initially is linearly related to the duration of circulatory arrest and rises more steeply after 50 minutes of ischemia24 (Fig. 14-4).
Prevalence of temporary (TE) neurologic dysfunction as a function of duration of circulatory arrest time. (Reproduced with permission from Kouchoukos NT, Karp RB, Blackstone EH, Doty DB, Hanley FL [eds]: Kirklin/Baratt-Boyes Cardiac Surgery, 3rd ed. New York, Churchill Livingstone, 2003, Figure 2-2.)
Based on these findings and accumulated experience, it appears that the majority of patients can support unharmed a circulatory arrest of 30 minutes at 18°C (Fig. 14-5), provided that electrocerebral silence has been obtained. No deficit, or only a transient neurologic dysfunction, is expected when the ischemic period extends to 40 minutes, provided that rewarming is performed correctly and hemodynamic stability is maintained postoperatively. With an arrest time of more than 40 minutes, neurologic deficit is prone to occur, particularly in high-risk patients, such as those presenting with diabetes, hypertension, or old age. Further cooling of the brain to 13 to 15°C reduces the risk and makes a deficit again less likely if the arrest time does not exceed 40 minutes, and renders it no more severe than a transient dysfunction if it lasts 50 minutes. In these cases, careful rewarming with close monitoring of cerebral activity, deep anesthesia, and hemodynamic stability are critical for a favorable outcome.
Probability of safe (absence of structural or functional damage) circulatory arrest according to duration. A. Estimate at nasopharyngeal temperatures of 37d, 28d, and 18d C. B. Estimate at 18d C with dashed lines representing 70% confidence limits. At 30 minutes, safe arrest is likely, and at 45 minutes, it is probable. Other data suggest that, at 45 minutes, damage will probably be only structural and without evident functional sequelae. (Reproduced with permission from Kouchoukos NT, Karp RB, Blackstone EH, Doty DB, Hanley FL [eds]: Kirklin/Baratt-Boyes Cardiac Surgery, 3rd ed. New York, Churchill Livingstone, 2003, Figure 2-9A, B.)
Outcomes after Selective Antegrade Cerebral Perfusion
Evaluating the benefit of SACP is a difficult task because most studies in the literature are limited by selection bias. The primary benefit of SACP is not to reduce the incidence of embolic events, but rather to increase the safe duration of hypothermic circulatory arrest and allow for the application of circulatory arrest under moderate temperatures.28,44 Thus, it is not surprising that the majority of clinical studies have demonstrated no reduction in the incidence of permanent stroke.27,45–49 Overall, permanent stroke incidences after SACP in the literature range from 1 to 16%,50,51 likely reflecting the diversity and complexity of the patient population in which SACP is used. Generally, however, permanent stroke after elective aortic surgery with SACP occurs in 2.5 to 5% of patients.50,52 The incidence of global neurologic dysfunction, which is caused by failure to appropriately protect the cerebrum, is reduced in patients who undergo SACP compared with DHCA alone.52 Furthermore, because SACP does not require deep hypothermia, other postoperative complications such as reintubation, renal failure, and ventilator times may also be reduced.52 There is also evidence that SACP may improve long-term survival, although the exact mechanism is not completely clear.52 Although prospective studies are lacking, it appears that SACP may be primarily advantageous in those situations in which a prolonged period of circulatory arrest is anticipated. These may include complex Type I aortic dissections and aortic arch reconstructions.
Outcomes after Retrograde Cerebral Perfusion
Recent clinical research using RCP has demonstrated encouraging results. A reduction in both mortality and neurologic damage has been documented regularly with the adjunctive use of retrograde cerebral perfusion compared with classic deep hypothermia alone.53–57 Some studies confirmed the limited capacity of retrograde perfusion to sustain cerebral metabolism.58,59 Yet, the inability of RCP to meet cerebral requirements does not indicate that it is ineffective as an adjunctive means of cerebral perfusion, because RCP has proved extremely effective at maintaining cerebral hypothermia as well as preventing intracellular acidosis, which may contribute to apoptosis and in turn result in temporary and/or permanent neurologic dysfunction.60
Most surgeons acknowledge the potential capacity of retrograde cerebral perfusion to prolong the period of safe circulatory arrest; however, it is generally not an adjunctive modality that is used for complex repairs in which a period of circulatory arrest of greater than 50 minutes is anticipated. This method should be viewed as a valuable but not an alternative adjunct to conventional methods when longer periods of circulatory arrest are anticipated. Some have found alternative uses of RCP that may prove to be beneficial. For example, at the Brigham and Women's Hospital we have recently adopted the use of DHCA with RCP for patients who undergo ascending aortic aneurysm repair to facilitate the creation of an open distal anastomosis, thereby allowing for the resection of all aneurysmal ascending aortic tissue. A recent study has demonstrated no overall difference in the incidence of neurologic events or mortality when compared with the standard aortic cross-clamp, closed distal anastomosis approach.61