Brain Protection Using Antegrade Selective Cerebral Perfusion: A Multicenter Study

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1 Brain Protection Using Antegrade Selective Cerebral Perfusion: A Multicenter Study Marco Di Eusanio, MD, Marc A. A. M. Schepens, MD, PhD, Wim J. Morshuis, MD, PhD, Karl M. Dossche, MD, PhD, Roberto Di Bartolomeo, MD, Davide Pacini, MD, Angelo Pierangeli, MD, Teruhisa Kazui, MD, Kazuhiro Ohkura, MD, and Naoki Washiyama, MD Department of Cardiopulmonary Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands, Department of Cardiac Surgery, Policlinico S Orsola, University of Bologna, Bologna, Italy, and First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan Background. To evaluate the results of antegrade selective cerebral perfusion as a method of brain protection during surgery of the thoracic aorta and to determine predictors of hospital mortality and adverse neurologic outcome. Methods. Between October 1995 and March 2002, 588 patients underwent aortic surgery with the aid of antegrade selective cerebral perfusion. There were 334 men (56.8%); the mean age was years. One hundred sixty-two patients (27.6%) underwent urgent operation. The separated graft technique was employed to reimplant the arch vessels in 230 patients (65.3%) of the 352 requiring aortic arch replacement. Associated procedures were performed in 254 patients (43.2%). One hundred twelve patients underwent elephant trunk procedure. The mean cerebral perfusion time was minutes. Results. The overall hospital mortality rate was 8.7%. A logistic regression analysis revealed urgent operation, recent central neurologic event, tamponade, unplanned coronary artery revascularization and pump time to be independent predictors of hospital mortality (p < 0.05). The permanent neurologic dysfunction rate was 3.8%. A logistic regression analysis showed tamponade to be independent predictor of permanent neurologic dysfunction (p < 0.05). The transient neurologic dysfunction rate was 5.6%. Recent central neurologic event, tamponade, coronary disease, and aortic valve replacement were indicated as independent predictors of transient neurologic dysfunction by logistic regression (p < 0.05). Conclusions. In our experience the utilization of antegrade selective cerebral perfusion resulted in encouraging results in terms of hospital mortality and brain complications. Neither the extent of the replacement nor the duration of the cerebral perfusion had an impact on hospital mortality and neurologic outcome. (Ann Thorac Surg 2003;76:1181 9) 2003 by The Society of Thoracic Surgeons Antegrade selective cerebral perfusion and deep hypothermic circulatory arrest with or without retrograde cerebral perfusion are widely accepted methods of brain protection during surgery of the thoracic aorta. In our institutions antegrade selective cerebral perfusion with moderate hypothermia is currently employed as a method of brain protection during aortic operations requiring a circulatory arrest longer than 30 minutes. The aim of the present study was to assess in a larger series of patients undergoing surgery of the thoracic aorta with the aid of antegrade selective cerebral perfusion the incidence of in-hospital death and adverse neurologic outcome and to identify among preoperative and intraoperative factors those that may result in death, permanent neurologic dysfunction, or transient neurologic dysfunction. Presented at the Thirty-ninth Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31 Feb 2, Address reprint requests to Dr Di Eusanio, Dipartimento di Cardiochirurgia, Ospedale Cardiologico GM Lancisi, Via Baccarani 6, Ancona, 60122, Italy; m_dieus@hotmail.com. Patients and Methods Between October 1995 and March 2002, 588 patients (Table 1) underwent operations on the thoracic aorta using antegrade selective cerebral perfusion and moderate hypothermia at St. Antonius Hospital (Nieuwegein, The Netherlands), at Sant Orsola Hospital (Bologna, Italy), and at Hamamatsu University (Hamamtsu, Japan). After defining common perioperative variables (see Appendix) the data were retrospectively collected and included in the study. As depicted in Table 2 there were 334 men (56.8%) and 254 women (43.2%) and the mean age was years. One hundred sixty-two patients (27.6%) underwent urgent operation. Indication for surgery was acute type A dissection in 152 patients (25.9%), chronic postdissection aneurysm in 143 (24.3%), and degenerative aneurysm in 293 (49.8%). Fifty-five patients (9.4%) had a history of central neurologic event, 84 (14.3%) had undergone previous cardiovascular operations through a median sternotomy. All elective operation patients underwent preoperative evaluation of cerebral circulation with Doppler ultrasonography of the extracranial vessels, dig by The Society of Thoracic Surgeons /03/$30.00 Published by Elsevier Inc PII S (03)

2 1182 DI EUSANIO ET AL Ann Thorac Surg ANTEGRADE SELECTIVE CEREBRAL PERFUSION 2003;76: Table 1. Study Centers St. Antonius Hospital, Nieuwegein, Netherlands University of Bologna, Bologna, Italy University of Hamamatsu, Hamamatsu, Japan Years and Number of Cases , n , n , n 126 ital subtraction angiography of the extracranial and intracranial circulation, or transcranial Doppler (TCD) ultrasonography study. Operative Technique Both anesthetic and antegrade selective cerebral perfusion management were similar in the three institutions. Induction of anesthesia was obtained with propofol 2 mg/kg, fentanyl 2 (mcg/kg and pancuronium 0.1 mg/kg. Anesthesia was maintained with propofol and fentanyl. For all patients ph balance control was carried out using the ( -stat method. No pharmacologic neuroprotective agents were administered. Aprotinine was used sporadically. Operations were performed through a median sternotomy in 583 (99.1%) patients and through a median sternotomy plus anterolateral thoracotomy in 5 (0.9%). After systemic heparinization cardiopulmonary bypass was instituted with a cannula for arterial return in the ascending aorta, in the femoral artery or in the right axillary artery, and a venous single-two stage cannula in the right atrium or a long venous cannula through the left femoral vein into the right atrium. The left side of the Table 2. Patient Profile Number Percent Age, years Age 70 years Male Aortic pathology Chronic aneurysm Acute type A dissection Postdissection aneurysm Impending aneurysmal rupture Urgency Preoperative renal insufficiency Preoperative COPD Hypertension Preoperative CVA (all combined) Recent CVA ( 6 months) Old CVA ( 6 months) CAD Acute aortic insufficiency Tamponade Redo CAD coronary artery disease; COPD chronic obstructive pulmonary disease; CVA cerebrovascular accident. heart was vented through the right superior pulmonary vein. Myocardial protection was achieved with cold crystalloid or blood cardioplegia. Details of our cannulation technique and method of antegrade selective cerebral perfusion with moderate hypothermic circulatory arrest have been previously described [1 5]. Briefly, after the cardiopulmonary bypass was instituted and the patients were cooled to 22 C to 26 C of nasopharyngeal temperature, systemic circulation was arrested and the diseased aorta opened. With the patient in the Trendelenburg position and under direct visual control, 15F retrograde coronary sinus perfusion cannulas (Medtronic DLP; Chase Medical, Houston, TX) or malleable cerebral perfusion catheters (Fuji System, Tokyo, Japan) [6] connected to the oxygenator with a separate single-roller pump head were inserted in the innominate and left common carotid arteries through the aortic lumen. The left subclavian artery was clamped or occluded with a Fogarty catheter (Baxter Health Care, Irvine, CA; IFM, Clearwater, FL) in order to avoid the steal phenomenon. The cerebral perfusion was started at a rate of 10 ml min 1 kg 1 and adjusted to maintain a right radial arterial pressure between 40 and 70 mm Hg. Temperature of the brain perfusate was 20 C. The introduction of the cerebral perfusion catheters usually took less than 3 minutes. Tools of cerebral monitoring included right radial arterial pressure line in all cases, electroencephalogram, regional oxygen saturation in the bilateral frontal lobes by means of a near-infrared spectroscopy (NIRS), jugular venous oxygen saturation, and TCD measurement of the blood velocity of the middle cerebral artery when available. Transesophageal echocardiography was routinely used. The extent of repair and the associated procedures performed are shown in Tables 3 and 4. En bloc [7] or separated graft techniques [4] were used to reimplant the arch vessels when a complete aortic arch replacement was performed. Perfusion data are showed in Table 5 and Figure 1. Statistical Analysis Continuous variables were expressed as the mean one SD and categorical variables as percentages. All preoperative and intraoperative variables were first analyzed using univariate analysis (unpaired two-tailed t test, 2 test, or Fisher s exact test when appropriate) to determine whether any single factor influenced hospital mortality and neurologic outcome. A p value of less than 0.05 was taken to indicate statistical significance. The analyses for permanent neurologic dysfunction (PND) and temporary neurologic dysfunction (TND) were conducted separately. Risk factors for PND (stroke or coma) were examined in all patients (n 574) who survived the operation long enough (24 to 36 hours) to undergo an appropriate neurologic evaluation, and risk factors for TND (postoperative confusion, agitation, delirium, prolonged obtundation or transient parkinsonism with negative brain CT scanning and complete resolution

3 Ann Thorac Surg DI EUSANIO ET AL 2003;76: ANTEGRADE SELECTIVE CEREBRAL PERFUSION 1183 Table 3. Surgical Techniques No. (%) Hospital Death PND TND No. (%) p No. (%) p No. (%) p Extent of replacement (n 588) Ascending aorta or hemiarch 230 (39.1) 27 (11.7) 10 (4.5) 13 (6.1) Ascending aorta plus arch 222 (37.8) 18 (8.1) 8 (3.7) 11 (5.3) Total thoracic aorta 82 (13.9) 4 (4.9) 3 (3.8) 5 (6.5) Arch plus descending aorta 16 (2.7) Isolated aortic arch 32 (5.4) 2 (6.3) 1 (3.1) 2 (6.5) Others 6 (1.1) Arch vessels reimplantation technique (n 352) Separated graft technique 230 (65.3) 15 (6.5) 9 (4.0) 12 (5.5) En bloc technique 122 (34.7) 9 (7.4) 3 (2.5) 6 (5.2) PND permanent neurological dysfunction; TND transient neurological dysfunction. before discharge) were assessed in all operative survivors without PND (n 552). Variables that achieved p less than 0.1 in the univariate analysis were examined using multivariate analysis by forward stepwise logistic regression to evaluate independent risk factors for hospital mortality, PND, and TND. Statistical analysis was performed using SPSS 8.0 software (SPSS, Chicago, IL). Results The overall in-hospital mortality rate of 8.7% (51 of 588) was 4.9% and 18.5% for elective and urgent surgery (p 0.000) respectively. Causes of death were multiorgan failure (n 23), neurologic damage (n 4), heart failure (n 8), respiratory failure (n 3), bleeding (n 5), bowel ischemia (n 1), rupture of a distal aneurysm (n 6), and rupture of a proximal anastomotic site (n 1). On univariate analysis the following factors had a significant influence on hospital mortality: urgent status (p 0.000), acute dissection (p 0.000), impending aneurysmal rupture (p 0.048), history of recent central neurologic event (p 0.005), preoperative renal insufficiency (p 0.048), tamponade (p 0.000), acute aortic insufficiency (p 0.008), unplanned coronary artery bypass graft ([CABG] p 0.017), cardiopulmonary bypass Table 4. Associated Procedures (n 588) No. Percent AVR Bentall Aortic root remodeling Homograft Aortic commisures resuspension Associated aortic procedures (all combined) CABG MVP/R Elephant trunk 112/ Associated procedures (all combined) AVR aortic valve replacement; CABG coronary artery bypass grafting; MVP/R mitral valve plasty/replacement. (CPB) time ( minutes versus minutes; p 0.000). Multivariate analysis revealed urgent status (p 0.005; odds ratio [OR] 2.7), history of recent central neurologic event (p 0.017; OR 4.7), tamponade (p 0.023; OR 2.7), unplanned CABG (p 0.047; OR 5.4), and CPB time (p 0.001; OR 1.01/min) to be independent predictors of hospital mortality (Table 6). Permanent neurologic dysfunction, which was evaluated in all patients who survived the operation and could undergo an adequate neurologic examination, was reported in 22 of 574 patients (3.8%). In univariate analysis, acute dissection (p 0.038), urgent status (p 0.014) and tamponade (p 0.028) showed statistically significant correlation with the occurrence of permanent neurologic dysfunction. On multiple logistic regression analysis, tamponade (p 0.000; OR 6.7) was found to be an independent predictor of permanent neurologic dysfunction (Table 7). Transient neurologic dysfunction, which was evaluated only in patients without permanent neurologic damages, occurred in 31 of 552 patients (5.6%). Age more than 70 years (p 0.043), acute dissection (p 0.027), urgent status (p 0.017), history of recent central neurologic event (p 0.003), coronary artery disease (p 0.024), tamponade (p 0.002), and aortic valve replacement (p 0.000) were associated with a significantly increased risk of TND on univariate analysis. Stepwise logistic regression indicated history of recent central neurologic event (p 0.000; OR 14.8), Table 5. Perfusion Data Minimum Maximum Mean SD CPB time Myocardial ischemic time Cerebral perfusion time Nasopharyngeal temperature Rectal temperature CPB Cardiopulmonary bypass.

4 1184 DI EUSANIO ET AL Ann Thorac Surg ANTEGRADE SELECTIVE CEREBRAL PERFUSION 2003;76: Table 7. Univariate and Multivariate Analysis for Permanent Neurologic Dysfunction Risk Factors No. PND (%) Univariate Multivariate p p OR 95% CI Acute type A dissection NS No Yes Urgency status NS No Yes Tamponade No Yes Fig 1. Distribution of patients by antegrade cerebral perfusion (ASCP) time. Black bar 45 minutes; dark gray bar 45 to 60 minutes; light gray bar 60 minutes. coronary artery disease (p 0.002; OR 4.7), tamponade (p 0.000; OR 7.8), and aortic valve replacement (p 0.000; OR 8.13) as independent predictors of TND (Table 8). The extent of the aortic repair and antegrade selective cerebral perfusion time (Figs 2 and 3, Table 3) CI confidence interval; NS not significant; OR odds ratio; PND permanent neurologic dysfunction. were not statistically correlated with an increased risk of hospital mortality, permanent and transient neurologic dysfunction. Other postoperative complications included bleeding requiring a repeat thoracotomy in 68 patients (12.1%), postoperative myocardial infarction (serum creatine kinase [CK] level 300 IU/L with a CK/MB fraction 3%) Table 6. Univariate and Multivariate Analysis for Hospital Mortality Risk Factors No. Death (%) Univariate Multivariate p p OR 95% CI Acute type A dissection NS No Yes Impending aneurysmal rupture NS No Yes Urgency status No Yes Preoperative renal insufficiency NS No Yes Recent CVA No Yes Acute aortic insufficiency NS No Yes Tamponade No Yes Unplanned CABG No Yes CPB time vs /min CABG coronary artery bypass grafting; CI confidence interval; CPB cardiopulmonary bypass; CVA cerebrovascular accident; NS not significant; OR odds ratio.

5 Ann Thorac Surg DI EUSANIO ET AL 2003;76: ANTEGRADE SELECTIVE CEREBRAL PERFUSION 1185 Table 8. Univariate and Multivariate Analysis for Transient Neurologic Dysfunction Risk Factors No. TND (%) Univariate Multivariate p p OR 95% CI Age 70 years NS No Yes Acute type A dissection NS No Yes Urgency status NS No Yes Recent CVA No Yes CAD No Yes Tamponade No Yes AVR No Yes AVR aortic valve replacement; CAD coronary artery disease; CI confidence interval; CVA cerebrovascular accident; NS not significant; OR odds ratio; TND transient neurologic dysfunction. in 17 patients (2.9%). Pulmonary complications requiring a mechanical ventilatory support longer than 5 days occurred in 104 patients (17.7%), renal failure requiring temporary hemodialysis occurred in 27 patients (4.6%). Fig 2. Distribution of hospital death (solid bars), permanent neurologic dysfunction (shaded bars), and transient neurologic dysfunction (open bars) by the extent of the aortic replacement in elective cases. (desc. descending.) Comment In the last decade the implementation of new methods of cerebral protection including antegrade and retrograde cerebral perfusion and the reduction of the brain embolic risk by means of alternative cannulation sites for CPB arterial return such as ascending aorta and more recently right or left axillary artery have contributed to improve hospital mortality and neurologic outcome in patients undergoing surgery of the aortic arch [8 11]. On the basis of experimental and clinical studies [12 16] we believe antegrade selective cerebral perfusion to be the safest method of brain protection especially when complex and time-consuming aortic repairs are anticipated. The extension of the safe time of circulatory arrest up to 90 minutes [1], the utilization of moderate hypothermia instead of profound hypothermia, the reduced CPB time required, and the better and more physiologic metabolic supply of oxygenated blood to the brain are considered advantages of this technique. Even though this study carries the risks inherent to the use of retrospective and multicenter data we chose to assess the incidence of in-hospital death and adverse neurologic outcome in a larger series of patients in order to identify among preoperative and intraoperative factors those that may result in death, permanent neurologic dysfunction, or transient neurologic dysfunction. In this series the overall hospital mortality was 8.7%. In 656 patients undergoing aortic surgery using deep hypothermic circulatory arrest, Svensson and colleagues [17] reported a hospital survival and a stroke rate of 88% and 7% respectively. An increased risk of stroke in patients treated with periods of circulatory arrest longer than 40 minutes and an increased early mortality for circulatory arrest time beyond 65 minutes were observed. Furthermore CPB time was indicated as a predictor for increased risk of early death by multivariate analysis. Ueda [18] reported a hospital mortality of 10% and a stroke rate of 4% in 249 patients undergoing aortic arch surgery using retrograde cerebral perfusion as a method of brain protection. Retrograde cerebral perfusion time, pump time, and advanced age were indicated as risk factors for hospital mortality on multivariate analysis. In our series apart from unplanned CABG documenting a higher risk of death when intraoperative technical problems occur the prolonged CPB time was indicated by logistic regression as the only intraoperative independent predictive risk factor for hospital mortality. This factor reflects the complexity of the aortic repair. In fact in our series a concomitant aortic procedure was performed in 33.7% of patients; in the 352 patients undergoing aortic arch replacement the separated graft technique and the elephant trunk technique were employed in 65.3% and 44% respectively (Table 4). However the extent of the aortic replacement and the duration of antegrade selective cerebral perfusion had no adverse impact on hospital mortality. Might it be speculated that if profound hypothermia, instead of moderate, was used in our series the hospital mortality might have been higher as a consequence of a further augmentation of the CPB time?

6 1186 DI EUSANIO ET AL Ann Thorac Surg ANTEGRADE SELECTIVE CEREBRAL PERFUSION 2003;76: Fig 3. Relation between duration of antegrade selective cerebral perfusion and hospital mortality (top), permanent neurologic dysfunction (bottom left), and transient neurologic dysfunction (bottom right). It has been suggested that strokes are caused by embolic events and transient neurologic dysfunctions are related to inadequate brain protection [19]. Therefore we prefer to cannulate the ascending aorta and in most recent cases the right axillary artery for instituting CPB and initiating antegrade perfusion through the side branch of the arch graft after completing the distal anastomosis to reduce embolization from the distal aorta. In our series the permanent neurologic dysfunction rate was 3.8%. Even though the separated graft technique surprisingly was not indicated as a protective factor for permanent neurologic dysfunction as compared to the en bloc technique during aortic arch replacement (Table 3), a further utilization of the separated graft technique and of the axillary artery as a cannulation site for CPB institution will probably contribute to further reduce the incidence of neurologic damages in our patients. Ergin and associates [19, 20] reported an overall TND rate of 19% to 28% using deep hypothermic circulatory arrest and an almost linear relationship between circulatory arrest time and the occurrence of TND was found. Okita and colleagues [13] in a recent prospective study comparing deep hypothermic circulatory arrest with retrograde cerebral perfusion and antegrade selective cerebral perfusion reported a significantly higher incidence of TND in the retrograde cerebral perfusion group (33% versus 13.3%, p 0.05) especially when the retrograde cerebral perfusion duration was longer than 50 minutes. A significant correlation between the degree of TND and the duration of brain circulatory arrest was also demonstrated. Hagl and colleagues [12] reported an higher rate of TND with retrograde cerebral perfusion than with antegrade selective cerebral perfusion in a group of 91 patients who required a cerebral protection time between 40 and 80 minutes. Furthermore retrograde cerebral perfusion resulted in no reduction of TND compared with deep hypothermic circulatory arrest alone. In our series, the TND rate was 5.6%. Although we did not perform extensive psychological testing as in the studies by the above mentioned groups the difference remains important. In conclusion antegrade selective cerebral perfusion and moderate hypothermia is confirmed to be a safe method of cerebral protection. Complex and time consuming repairs of the thoracic aorta could be performed with encouraging hospital survival and acceptable neurologic outcome. Urgent operation and prolonged pump time still remain important risk factors for hospital mortality and adverse neurologic outcome. References 1. Di Eusanio M, Schepens MA, Morshuis WJ, Di Bartolomeo R, Pierangeli A, Dossche KM. Antegrade selective cerebral

7 Ann Thorac Surg DI EUSANIO ET AL 2003;76: ANTEGRADE SELECTIVE CEREBRAL PERFUSION 1187 perfusion during operations on the thoracic aorta: factors influencing survival and neurologic outcome in 413 patients. J Thorac Cardiovasc Surg 2002;124: Dossche KM, Schepens MA, Morshuis WJ, Muysoms FE, Langemeijer JJ, Vermeulen FE. Antegrade selective cerebral perfusion in operations on the proximal thoracic aorta. Ann Thorac Surg 1999;67: Di Bartolomeo R, Pacini D, Di Eusanio M, Pierangeli A. Antegrade selective cerebral perfusion during operations on the thoracic aorta: our experience. Ann Thorac Surg 2000;70: Kazui T, Washiyama N, Muhammad BA, et al. Total arch replacement using aortic arch branched grafts with the aid of antegrade selective cerebral perfusion. Ann Thorac Surg 2000;70: Kazui T, Washiyama N, Muhammad BA, et al. Extended total arch replacement for acute type A aortic dissection: experience with seventy patients. J Thorac Cardiovasc Surg 2000;119: Kazui T. Simple and safe cannulation technique for antegrade selective cerebral perfusion. Ann Thorac Cardiovasc Surg 2001;7: Pearce C, Weichert R, del Real R. Aneurysms of aortic arch. Simplified technique for excision and prosthetic replacement. J Thorac Cardiovasc Surg 1969: Bachet J, Guilmet D, Goudot B, et al. Cold cerebroplegia. A new technique of cerebral protection during operations on the transverse aortic arch. J Thorac Cardiovasc Surg 1991; 102: Ueda Y, Miki S, Okita Y, et al. Protective effect of continuous retrograde cerebral perfusion on the brain during deep hypothermic systemic circulatory arrest. J Card Surg 1994;9: Westaby S, Katsumata T. Proximal aortic perfusion for complex arch and descending aortic disease. J Thorac Cardiovasc Surg 1998;115: Sabik JF, Lytle BW, McCarthy PM, Cosgrove DM. Axillary artery: an alternative site of arterial cannulation for patients with extensive aortic and and peripheral vascular disease. J Thorac Cardiovasc Surg 1995;109: Hagl C, Ergin MA, Galla JD, et al. Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients. J Thorac Cardiovasc Surg 2001;121: Okita Y, Minatoya K, Tagusari O, Ando M, Nagatsuka K, Kitamura S. 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: Sakurada T, Kazui T, Tanaka H, Komatsu S. Comparative experimental study of cerebral protection during aortic arch reconstruction. Ann Thorac Surg 1996;61: Tanaka H, Kazui T, Sato H, Inoue N, Yamada O, Komatsu S. Experimental study on the optimum flow rate and pressure for selective cerebral perfusion. Ann Thorac Surg 1995;59: Yamashita K, Kazui T, Terada H, Washiyama N, Suzuki K, Bashar AH. Cerebral oxygenation monitoring for total arch replacement using selective cerebral perfusion. Ann Thorac Surg 2001;72: Svensson LG, Crawford ES, Hess KR, et al. Deep hypothermia with circulatory arrest. Determinants of stroke and early mortality in 656 patients. J Thorac Cardiovasc Surg 1993;106: Ueda Y, Okita Y, Aomi S, Koyanagi H, Takamoto S. Retrograde cerebral perfusion for aortic arch surgery: analysis of risk factors. Ann Thorac Surg 1999;67: Ergin MA, Uysal S, Reich DL, et al. Temporary neurological dysfunction after deep hypothermic circulatory arrest: a clinical marker of long-term functional deficit. Ann Thorac Surg 1999;67: Ergin MA, Galla JD, Lansman S, Quintana C, Bodian C, Griepp RB. Hypothermic circulatory arrest in operations on the thoracic aorta. Determinants of operative mortality and neurologic outcome. J Thorac Cardiovasc Surg 1994;107: Appendix Preoperative, Intraoperative, and Postoperative Variables Included in Analysis Age Sex Aortic pathology (chronic aneurysm; acute type A aortic dissection; postdissection aneurysm) Acute type A aortic dissection Impending aneurysmal rupture Status (elective;urgent) Preoperative renal insufficiency (serum creatinine 250 (mmol/l) Preoperative chronic obstructive pulmonary disease (FEV1 50% to 70%, medical therapy) Hypertension Preoperative recent central neurologic events (stroke or transient ischemic attack 6 months) Preoperative old central neurologic events (stroke or transient ischemic attack 6 months) Preoperative neurologic events (all combined) History of coronary artery disease (myocardial infarction, positive result to whatever diagnostic investigation for coronary artery disease) Acute aortic insufficiency ( 2/4) Tamponade (blood in pericardium with hemodynamic instability) Previous cardiovascular operation through median sternotomy Surgical approach (median sternotomy; median sternotomy plus left anterolateral thoracotomy) Extent of aortic replacement (isolated aortic arch; ascending aorta plus arch; total thoracic aorta; arch plus descending thoracic aorta, ascending aorta or hemiarch, others) Arch vessels reimplantation (en bloc technique; separated graft technique) Concomitant aortic valve replacement Concomitant Bentall procedure Concomitant aortic root remodelling Concomitant homograft Concomitant aortic valve commisures resuspension Concomitant coronary artery bypass grafting Concomitant mitral valve replacement or repair Concomitant elephant trunk Associated procedures (all combined) Cardiopulmonary bypass time (minutes) Myocardial ischemic time (minutes) Antegrade selective cerebral perfusion time (minutes) Lowest nasopharingheal temperature ( C) Lowest rectal temperature ( C) Death during hospitalization Cause of death

8 1188 DI EUSANIO ET AL Ann Thorac Surg ANTEGRADE SELECTIVE CEREBRAL PERFUSION 2003;76: Permanent neurologic damage (stroke, coma, new focal or multiple brain lesion detected by means of CT scan or MRI) Transient neurologic dysfunction (postoperative confusion, agitation, delirium, prolonged obtundation, or transient parkinsonism with negative brain CT scanning and complete resolution before discharge) DISCUSSION DR RANDALL B. GRIEPP (New York, NY): I would like to congratulate Dr Di Eusanio and his colleagues on a spectacular clinical report. This I think is the largest series of aortic arch replacements reported at one time, and the results are of benchmark quality. I would like to pay tribute also to Dr Kazui, one of the coauthors, who has championed the use of selective cerebral perfusion in this setting since the early 1980s. This was a cooperative study involving two institutions in addition to Dr Kazui s and clearly attests to the importability of his technique to other institutions and its use by other surgeons. I would like to thank the Program Committee for giving me the opportunity to discuss a paper in which the results are so excellent, since in these circumstances one need pull no punches and can be as critical as possible. First of all, I believe this paper helps to put to rest the argument as to what is the optimal brain protection technique for arch and proximal aortic surgery. The use of long periods of hypothermic circulatory arrest, that is, in my view, longer than 30 minutes, or retrograde cerebral perfusion I believe are of historical interest only, and I would like to ask Dr Di Eusanio if there are any circumstances in which he would prefer long periods of HCA or RCP in this setting? The second point is that the results were excellent here with a hospital mortality rate of 8.7% and a rate of permanent neurological deficit of 3.8%. I continue to believe, however, that it is useful to report the results in terms of adverse outcome, that is, either death or permanent neurologic deficits, since I think this number is the most useful one to a patient in contemplating undergoing an elective procedure. I would like to ask Dr Di Eusanio whether he can estimate what their overall rate of adverse outcome is. This could range from 8.7% if all the patients with strokes died or as high as 12.5% if they all survived. A third point is we were convinced a number of years ago by Dr Kazui and Dr Bachet and by work in our own laboratory that selective cerebral perfusion was the preferred way of protecting the brain. We have utilized this technique since 1994 and since 2000 have refined it further utilizing a technique in which we use a period of circulatory arrest, up to 30 minutes, to dissect, transect, and anastomose the three arch vessels to a trifurcated graft, which is then perfused by the axillary artery while the remainder of the procedure is carried out. I believe, of course, that there are some advantages to this method over the one utilized in this paper and that will give rise to several questions. I am concerned a little bit about the placement of balloon catheters in the cerebral vessels. In many instances, particularly in older patients, in the origins of the arch vessels, there is a fair amount of atherosclerotic debris present. This may go up for a centimeter or two. What do Dr Di Eusanio and his colleagues do to prevent embolizing particulate material from the proximal portion of the vessels? The use of perfusion catheters makes it necessary to monitor very carefully cerebral perfusion because obstruction to the catheters can occur at the tip or by kinking of the catheters. Does Postoperative renal insufficiency requiring hemodialysis Postoperative respiratory insufficiency requiring mechanical ventilatory support more than 5 days Postoperative myocardial infarction (electrocardiography, serum CK level 300 IU/L with CK/MB fraction 3%) Bleeding requiring rethoracotomy the need to monitor near-infrared spectroscopy, carotid Dopplers, and so forth complicate the operative procedure? The technique utilized here utilizes clamping rather than perfusing the left subclavian artery. This simplifies the procedure to some extent but in my own view there are some problems with this. One clearly eliminates steal into the operative field but steal still does occur into the left shoulder and arm and I think if one is going to utilize this technique it is necessary to perform a fairly extensive preoperative evaluation to assure that the posterior brain circulation on the left is not dependent on the left vertebral. Have Dr Di Eusanio and his colleagues considered perfusing the left subclavian artery as well as the other two arch vessels during the period of selective perfusion? Finally, the degree of hypothermia utilized here is what I would consider moderate, that is, 22 to 25 degrees for the rest of the body, and I would be interested to know if the authors have any information regarding the ischemic tolerance of the lower body, particularly the spinal cord, at this temperature; that is, did they see any evidence of distal ischemic damage in the patients who had the long periods of lower body ischemia? And finally, have they ever seen as we have occasionally in some of these patients, particularly obese ones, a considerable washout of lactate during the first few hours after surgery, probably from ischemia that occurs in poorly cooled beds exacerbated by the period of lower body ischemia? Once again, let me congratulate the authors. My criticisms and questions are basically quibbles about the last tenth of a second in a hundred meter race. This is a spectacular report and I congratulate them on their accomplishment. DR DI EUSANIO: Thank you, Dr Griepp, for your kind comments and several questions. In our institutions, deep hypothermia and circulatory arrest is considered as a safe method of brain protection if the duration of the circulatory arrest is shorter than 30 minutes. If a more complex and time-consuming aortic operation is performed, then antegrade selective cerebral perfusion is our method of choice. We had a very limited experience with retrograde cerebral perfusion. Our results were comparable with those obtained with deep hypothermia and circulatory arrest alone and our results substantially improved after we switched to antegrade selective cerebral perfusion, especially in complex aortic repairs. Doctor Griepp is used to looking at the patient s outcome combining together the hospital mortality rate and the stroke rate. We do not do that. We look at hospital mortality and permanent neurologic dysfunction in a separate way. However, trying to give an adverse outcome rate according to his definition, that would be around 11%, I believe. Is the cannulation of the arch vessels making the procedure more complex? We do not think so. In the presence of clots or plaque in the aortic arch and on the arch vessels, the separated graft technique has to be considered as an optimal option

9 Ann Thorac Surg DI EUSANIO ET AL 2003;76: ANTEGRADE SELECTIVE CEREBRAL PERFUSION 1189 reducing the embolic risk. I think it is important to transect the arch vessels 1 cm or 2 cm from the junction with the aortic arch where the likelihood of dislodging debris is low. The cannulation of the arch vessels is done under direct visualization. The balloons and the tip of the cannula are not traumatic and placed even more distally. So I think that, at least in our experience, the cannulation of the arch vessels did not result in an increased risk of brain embolism. We had a stroke rate of 3.8%. That was 2.2% in elective cases. Neuromonitoring is indeed essential. Nearinfrared spectroscopy, transcranial Doppler, and bilateral radial artery lines are all tools that do not crowd the operative area since they are applied far away from the surgical field. Our platform of cerebral monitoring can be set up in about 15 minutes and information about cerebral protection is of paramount importance. In our institutions all electively operated on patients undergo a preoperative evaluation of the cerebral circulation. In patients with a complete circle of Willis and no extracranial vascular pathologies, we normally perfuse the innominate artery and the left common carotid artery using two balloon catheters. The left subclavian artery is blocked using a Fogarty catheter or a clamp in order to avoid the steal phenomenon. This technique certainly simplifies the procedure but I do agree that some of the blood may go to the left arm. In cases where the preoperative evaluation shows us that the posterior part of the brain is dependent on the left vertebral artery we will not hesitate to introduce a third balloon catheter into the left subclavian artery in order to avoid hypoperfusion of this area. With concern to the possibility of having spinal cord injuries, we did not have any new paraplegia after surgery. Doctor Kazui demonstrated in a paper from 1992 that using antegrade selective cerebral perfusion and moderate hypothermia, a period of 90 minutes has to be considered as safe in terms of spinal cord protection but also in terms of hepatic and renal function preservation. With regard to the question involving obese patients showing washout of lactate during the first few hours after surgery, probably in every patient in whom the circulation to the lower body is restarted, a certain amount of acidosis and lactate will enter the circulation. But on the other hand, we have not observed this frequently.