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Ann Thorac Surg 1995;59:1308-1311
© 1995 The Society of Thoracic Surgeons
Department of Anaesthesia, University Hospital, University of Western Ontario, London, Ontario, Canada
Abstract
Recent developments in techniques for managing cardiopulmonary bypass are outlined with a view toward interventions aimed at decreasing the incidence of perioperative central nervous system dysfunction and overt stroke. Recent reports assessing central nervous system dysfunction after hypothermic and normothermic cardiopulmonary bypass are reviewed and critiqued along with data assessing techniques for cerebral protection during hypothermic circulatory arrest. Controversy surrounding optimal pH management is explored along with a proposal that pH-stat may be most satisfactory to ensure better brain cooling where circulatory arrest is anticipated, whereas alpha-stat may avoid cerebral hyperemia and thus decrease the cerebral embolic load during moderate hypothermic cardiopulmonary bypass. Newer developments in cerebral monitoring techniques are also reviewed.
Since the successful clinical introduction of cardiopulmonary bypass (CPB) by Gibbon [1] in 1953, there have been continual and ongoing improvements in the equipment and techniques associated with its use. Concomitantly, there has been a progressive increase in age, degree of comorbidity, and severity of atherosclerotic disease of patients seen for cardiac operations [2]. This has resulted in an increased incidence of postoperative neurologic injury, a factor assuming even greater importance in patient outcomes. Variables associated with central nervous system (CNS) dysunction after CPB include the following: normothermic rather than hypothermic CPB, lack of arterial line filtration, symptomatic versus asymptomatic carotid stenosis, severity of aortic atherosclerosis, and pH-stat versus alpha-stat management.
In a review of more than 24,000 patients undergoing coronary artery bypass grafting (CABG) procedures, a considerable increase in patient deaths causally related to adverse neurologic events was observed in the decade between 1970 and 1980 [2]. In this series, from 1970 to 1973, 8% of deaths among CABG patients were attributable to neurologic injury, and from 1980 to 1983, the proportion had increased to 20% of all CABG patient deaths.
Currently, clinical management strategies during CPB are undergoing profound change. Renewed interest in normothermic versus hypothermic perfusion during CPB has resulted in apparently contradictory results regarding patient outcomes. Much effort is being devoted to defining the physiologic responses of the brain to various alterations during CPB (eg, pH strategy, normothermia versus hypothermia, pulsatile or nonpulsatile perfusion, use of arterial line filtration, circulatory arrest, and retrograde cerebral perfusion). In addition, prospective studies are examining the impact of diverse strategies on neuropsychologic and neurologic outcomes after CPB to define optimal management techniques.
It has been suggested that nonpulsatile perfusion is implicated in stasis of cerebral interstitial fluid and may result in cerebral edema [3], as demonstrated by Harris and associates [4] using magnetic resonance imaging in patients after nonpulsatile CPB. Pulsatile cerebral perfusion was shown to improve cerebral gray matter to white matter flow ratios and cerebral oxygen consumption better than nonpulsatile perfusion in a canine model after 15 minutes of complete cardiac arrest [5]. Whether pulsatile perfusion as currently produced during CPB will result in improved neurologic outcomes appears unlikely, however. In a recent study, my colleagues and I [6] were unable to demonstrate any influence of mode of perfusion on neurobehavioral outcomes in a prospective study of 316 patients randomized to pulsatile or nonpulsatile perfusion during CABG.
pH Management
The influence of pH management strategy was assessed by Stephan and co-workers [7] in a prospective, randomized trial involving 65 patients undergoing CABG. These authors demonstrated a higher incidence of neurologic dysfunction at 7 days postoperatively in a group undergoing pH-stat management as opposed to the group managed using alpha-stat, and they also noted cerebral hyperemia during CPB, an observation consistent with findings in previous studies [8, 9]. A beneficial effect of alpha-stat strategy was also demonstrated in a larger series of 316 patients undergoing CABG [5]. There was a lower incidence of cognitive dysfunction 2 months after CABG in patients managed using alpha-stat than in those in whom pH-stat strategy was employed.
These results demonstrating a decreased incidence of neurobehavioral dysfunction with alpha-stat during moderate hypothermic CPB may relate to the preservation of cerebral autoregulation and lower cerebral blood flow associated with the alpha-stat strategy [7–9]. In turn, this may result in a decrease in delivery of cerebral emboli into the cerebral circulation. Further evidence of the role of microemboli in the genesis of CNS injury after CPB was presented by Waaben and associates [10]. Increased cerebral glucose consumption and greater regional cerebral capillary diffusion capacity during normothermic CPB were demonstrated in dogs in which an arterial line filter was placed proximal to the inflow cannula. Incorporation of an arterial filter was thought to provide better substrate delivery to brain tissue by preserving capillary perfusion through trapping of microbubbles and platelet microaggregates.
Normothermia Versus Hypothermia for Coronary Surgery
Improved myocardial performance has been reported after normothermic CPB and has prompted several outcome studies to assess the efficacy of this therapy. Because of apparently contradictory results from two of these large prospective studies, particular focus is now centered on CNS outcomes. The Warm Heart Surgery Investigators [11] from Toronto assessed 1,732 patients and reported a decreased incidence of low-output syndrome and lower cardiac isoenzyme fractions in patients randomized to normothermic perfusion compared with a group undergoing hypothermic CPB, but there was no difference in stroke rate, 1.6% versus 1.5%, respectively. In a comparable study by Martin and colleagues [12], 1,001 patients were similarly randomized to warm or cold CPB, and again marginally better myocardial protection was demonstrated with warm CPB. There was, however, a significantly higher rate of stroke in the warm group compared with the hypothermic CPB group, 3.1% versus 1.0%.
Reasons for this striking difference in stroke rate despite the use of two apparently similar techniques at different centers are not apparent, but it does appear as though the group reported by Martin and co-workers [12] was at higher risk, as there were more diabetics (25% versus 5.5%), and more of the patients had undergone prior CABG (14.5% versus 8% with prior vascular operation) than in the Toronto trial. In addition, it appears as though the temperatures in the Toronto normothermic group were allowed to drift between 34°C and 36°C [11], whereas the normothermic group reported by Martin and colleagues [12] was much more rigorously maintained at 37°C.
These temperature differentials may seem of little clinical significance, but as shown in animal studies of brain ischemia, small differences in brain temperature can profoundly influence the release of excitatory amino acids [13] and may confer substantial cerebral protection [14]. It is clear that the issue of normothermic versus hypothermic perfusion is far from settled, and currently many cardiac centers are opting for an intermediate course with temperatures ranging between 32° and 35°C.
Recently, physiologic studies assessing cerebral oxygenation during normothermic or hypothermic CPB have been described. In patients undergoing normothermic CPB, continuous jugular venous oximetry has demonstrated a higher incidence and extent of cerebral venous oxygen desaturation compared with those undergoing hypothermic CPB [15]. Whether this potential cerebral stress is etiologic in producing overt stroke in a high-risk subset of patients, eg, diabetics (who apparently constituted a greater proportion of the patients in the study of Martin and coauthors [12]), or whether other, more subtle technical differences, eg, temperatures maintained during normothermia, account for the differing stroke rates after normothermic CPB remains unclear, as does the current status of normothermic CPB for CABG procedures.
Cerebral Protection During Deep Hypothermic Circulatory Arrest
Temperature, pH management, selective cerebral perfusion, and specific pharmacologic intervention all may have a potential role in decreasing cerebral injury in patients undergoing deep hypothermic circulatory arrest (DHCA). It has been demonstrated that in immature pigs after 60 minutes of DHCA at 15°C, faster recovery of intracellular pH and cerebral high-energy phosphates and lower brain water content are seen with pH-stat than alpha-stat pH management [16]. Enhanced brain cooling as a result of increased subcortical blood flow in animals in which pH-stat was used prior to the onset of circulatory arrest is a likely rationale for the observed differences in results. Possibly reflecting this mechanism, lower carbon dioxide tension (alpha-stat) prior to DHCA but not during DHCA was associated with a worse developmental outcome at 48 months in a nonrandomized, retrospective case-control review [17] of 16 pediatric patients undergoing DHCA.
Maximum safe duration of DHCA at 15°C was assessed in neonatal pigs and found to be 70 minutes, after which ischemic lesions became apparent within the cerebellar region [18]. In adult dogs undergoing 120-minute DHCA at either 18° to 20°C or 5° to 7°C and subjected to neurologic scoring and brain histology 72 hours after recovery, better neurologic scores and a lesser extent of histologic injury were demonstrated after profound hypothermia, findings implying that profound hypothermia may be more advantageous where prolonged arrest is anticipated [19].
Selective cerebral perfusion has been employed both experimentally and in several clinical series in an attempt to decrease cerebral ischemia attending DHCA. In 11 adult patients undergoing aortic arch aneurysm repair, continuous retrograde cerebral perfusion at 15° to 24°C was employed during systemic circulatory arrest [20]. This study demonstrated the feasibility of this technique, which resulted in the survival of all patients, though 1 patient did sustain an (apparently) embolic stroke. In 56 4-week old piglets undergoing 120 minutes of DHCA at 15°C, intermittent antegrade carotid perfusion with crystalloid perfusate, University of Wisconsin solution containing allopurinol, adenosine, glutathione, and lactobionate, or University of Wisconsin solution containing the excitatory neurotransmitter antagonist MK-801 provided lower brain temperatures and improved recovery of cerebral high-energy phosphates and lower brain water content in all animals compared with a nonperfused control group [21]. Similar to other studies, lowered brain temperature as a result of continuous hypothermic perfusion was likely the greatest benefit. Whether washout of neurotoxic metabolites and enhanced metabolic recovery with University of Wisconsin solution also may be of assistance where prolonged hypothermic circulatory arrest is necessary remains to be verified.
In a clinical series [22] of 183 adult patients undergoing DHCA for aortic arch operations without selective cerebral perfusion but with ice packing to the head, temporary postoperative neurologic dysfunction was found in 19% of patients and correlated with age and increasing duration of DHCA. The incidence of stroke was 11% and also correlated with increasing age and with the presence of clot or atheroma in the aorta, factors receiving increasing recognition as independent risks for perioperative stroke.
Monitoring and CNS Injury
Selection of the optimal cannulation site by employing transesophageal echocardiography (TEE) to assess the extent of aortic atherosclerotic plaque has been receiving increased attention [23, 24]. To evaluate and grade the extent of aortic atherosclerosis, Marschall and colleagues [23] employed TEE and demonstrated a strong correlation between increasing age and severity of aortic disease. There was a 20% incidence of severe disease in patients older than 70 years and a strong association between perioperative stroke and severity of aortic arch disease. Modification of the cannulation site under TEE guidance to decrease stroke risk, particularly in the elderly, is an attractive possibility [24].
Transesophageal echocardiography is also being assessed in open heart procedures for its ability to detect and guide removal of retained intracardiac air [25]. Using TEE, residual air was still demonstrable after standard deairing maneuvers and was found to be located particularly in the upper pulmonary vein and left ventricular apex. Elimination of further air was enhanced under TEE guidance, but CNS outcome was not assessed. Thus, the clinical role of TEE–directed aspiration of air is currently unclear.
Using a fiberoptic catheter placed retrograde into the superior bulb of the jugular sinus, continuous monitoring of cerebral jugular venous oxygen saturation is being evaluated in an effort to identify instances of cerebral jugular venous oxygen desaturation, ie, a cerebral jugular venous oxygen saturation of less than 50%, during CPB [15, 26]. In a clinical study [26], good correlation was found between laboratory co-oximeter measurements and in vivo oximetry when assessed during normothermia, hemodilution, and hypothermia in 11 patients undergoing CPB. In a clinical feasibility study [27] assessing continuous monitoring of cerebral perfusion, the right internal jugular vein in 10 patients undergoing hypothermic CPB was cannulated with an intravascular Doppler catheter. Blood flow velocity was compared with intraoperative Kety-Schmidt measurement of cerebral blood flow and demonstrated good correlation between percent change in cerebral blood flow between techniques. Whether this technique will enable accurate quantification of cerebral blood flow or, more likely, will primarily reflect relative change in cerebral blood flow remains unclear, as does the role of this technique in assessing cerebral hemodynamic responses in clinical practice.
Conclusions
Given the aging of the surgical population and the generally more advanced degree of atherosclerosis of this population, the various manifestations of CNS injury occurring after cardiac surgical procedures are becoming an increasingly important issue. Although CNS injury after cardiac operations is a complex and multifaceted problem, some patterns are beginning to emerge. Increasingly, evidence points to cerebral embolization from either the CPB circuit or the aorta and great vessels as the primary mechanism producing cerebral injury. Strategies for assessment of patients at risk, and appropriate modification of cannulation and conduct of CPB are being defined. Cerebrovascular risks associated with normothermic CPB remain unclear, and ``mild hypothermia'' (eg, 32°C to 35°C) appears to be the current clinical compromise.
Management of pH during hypothermia is also undergoing reevaluation because of the increasing recognition that pH strategy must be tempered to the procedure. For example, where brain ischemia resulting from circulatory arrest is the primary concern, pH-stat may be preferable in that it provides more uniform brain cooling. However, for CABG, where cerebral emboli are the greatest risk, the evidence favors alpha-stat as providing marginally better cerebral protection.
Footnotes
Presented at the Conference on CNS Dysfunction After Cardiac Surgery: Defining the Problem, Fort Lauderdale, FL, Dec 10–11, 1994.
Address reprint requests to Dr Murkin, Department of Anaesthesia, University Hospital, 339 Windermere Rd, London, Ont, Canada N6A 5A5.
References
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