Hypothermic cardiopulmonary bypass with intervals

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1 Safety and Efficacy of Hypothermic Cardiopulmonary Bypass and Circulatory Arrest for Operations on the Descending Thoracic and Thoracoabdominal Aorta Nicholas T. Kouchoukos, MD, Paolo Masetti, MD, Chris K. Rokkas, MD, Suzan F. Murphy, RN, and Eugene H. Blackstone, MD The Heart Center, Missouri Baptist Medical Center, St. Louis, Missouri, and The Cleveland Clinic Foundation, Cleveland, Ohio Background. Hypothermic cardiopulmonary bypass with circulatory arrest is an important adjunct for operations on the distal aortic arch and the descending thoracic and thoracoabdominal aorta. Its safety and efficacy compared with other techniques (eg, simple aortic clamping, partial cardiopulmonary bypass, and regional hypothermia) are not clearly established. Methods. One hundred sixty-one patients (ranging from 20 to 83 years old) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the involved aortic segments using hypothermic cardiopulmonary bypass usually with intervals of circulatory arrest (mean interval, 38 minutes). Results. The 30-day mortality rate was 6.2% (10 patients). It was 41% (7 of 17) for patients having emergent operations (rupture or acute dissection) and 2.1% (3 of 144) for all other patients (p < 0.001). The 90-day mortality rate was 11.8% (19 patients). Paraplegia occurred in 4 and paraparesis in 1 of the 156 operative survivors whose lower limb function could be assessed postoperatively (3.2%). Among the 91 survivors with thoracoabdominal aortic disease, early paraplegia occurred in 1 of 33 patients with Crawford type I disease, 0 of 34 with type II disease, and 2 of 24 with type III disease. One patient (type II disease) had development of paraplegia on the tenth postoperative day. None of the 50 patients with aortic dissection experienced paralysis. Renal dialysis was required in 4 (2.5%) of the 157 operative survivors, prolonged inotropic support (> 48 hours) in 17 (11%), reoperation for bleeding in 8 (5%), mechanical ventilation (> 48 hours) in 31 (20%), and tracheostomy in 13 (8%). Three patients (1.9%) sustained a stroke. Conclusions. Hypothermic cardiopulmonary bypass provides safe and substantial protection against paralysis and renal, cardiac, and visceral organ system failure that equals or exceeds that of other currently used techniques but without the need of other adjuncts. (Ann Thorac Surg 2001;72: ) 2001 by The Society of Thoracic Surgeons Presented at the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29 31, Address reprint requests to Dr Kouchoukos, Cardiac, Thoracic and Vascular Surgery, Inc, 3009 N Ballas Rd, Suite 266C, St. Louis, MO 63131; ntkouch@aol.com. Hypothermic cardiopulmonary bypass with intervals of circulatory arrest using an anterior approach, usually through a median sternotomy, is a widely used technique for protection of the central nervous system during operations for the treatment of some congenital and acquired cardiac lesions and conditions that require resection or open exposure of the aortic arch. It is increasingly being used for operations on the distal aortic arch and the descending and thoracoabdominal aorta that necessitate posterolateral exposure [1 3]. In the latter setting, its advantages over other techniques such as simple aortic clamping, partial cardiac or total cardiopulmonary bypass, and regional hypothermia include minimal aortic dissection, elimination of the need of proximal and sequential aortic clamping, access to the proximal aortic arch, a bloodless field, return of the majority of the shed blood into the perfusion circuit, and protection by hypothermia of the central nervous system, the heart, and the abdominal organs [1]. Furthermore, use of other adjunctive measures, for example, cerebrospinal fluid drainage, monitoring of evoked potentials, separate perfusion of the renal and visceral arteries, and insertion of epidural catheters, is not necessary. Routine use of the technique has been questioned because of concern regarding a higher early mortality and a higher prevalence of complications compared with other techniques [4 6]. In 1995, we [1] reported our initial experience with the use of hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta in 51 patients. Here we summarize our total experience with this technique in 161 patients by The Society of Thoracic Surgeons /01/$20.00 Published by Elsevier Science Inc PII S (01)

2 700 KOUCHOUKOS ET AL Ann Thorac Surg HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 2001;72: Table 1. Patient Characteristics a Variable No. of Patients (n 161) Comorbidity Hypertension 114 (71) History of smoking 104 (65) Hyperlipidemia 54 (34) Chronic obstructive lung disease 49 (30) Coronary artery disease 46 (29) Peripheral vascular disease 32 (20) Creatinine 1.5 mg/dl 19 (12) History of TIA or stroke 17 (11) Diabetes 5 (3) Previous operations Proximal aortic repair 58 (36) Distal aortic repair 15 (9) Abdominal aortic aneurysm repair 24 (15) Aortic coarctation repair 6 (4) Aortic valve procedure 50 (31) Coronary artery bypass grafting or 31 (19) percutaneous intervention Cause of aortic disease Degenerative 94 (58) Rupture of aneurysm 11 Dissection 50 (31) Chronic 44 Acute 6 Other 17 (11) a Numbers in parentheses are percentages. TIA transient ischemic attack. Material and Methods Patient Selection Between January 1986 and November 2000, 161 patients with aortic disease involving the distal aortic arch, the descending thoracic aorta, or the thoracoabdominal aorta underwent resection and graft replacement of the diseased aortic segments using hypothermic cardiopulmonary bypass usually in combination with a period of circulatory arrest. The aorta was approached through a left posterolateral thoracotomy in all patients, with extension of the incision into the abdomen when indicated. The patients ranged in age from 20 to 83 years (mean age, years). Sixty-two patients (39%) were 70 years of age or older. Sixty percent of the patients were male, and 22 patients (14%) had clinical manifestations of Marfan s syndrome. Ninety-seven patients (60%) had symptoms referable to the aortic disease, and 64 (40%) had aneurysms that were more than twice the size of the adjacent normal aorta or had evidence by serial tomographic studies of progressive enlargement of the aorta. Seventeen patients (11%) required emergent operation for rupture of an aneurysm or for acute type B aortic dissection. Clinical characteristics of the patients, previous operations on the aorta and the heart, and causes of the aortic disease are shown in Table 1. The Society of Thoracic Surgeons National Database definitions were used for characterization of the preoperative variables [7]. One hundred three patients had had one or more previous operations on the thoracic or abdominal aorta or the aortic valve or had had myocardial revascularization. Degenerative disease with aneurysm was the most common indication for operation. The extent of the aortic disease requiring replacement is shown in Table 2. The decision was made to use hypothermic cardiopulmonary bypass and circulatory arrest in 25 patients because the location and the severity of the aortic disease precluded the safe placement of clamps on the aortic arch or the proximal descending thoracic aorta. In the remaining 136 patients, the technique was used because the aortic disease involved most or all of the descending thoracic aorta (40 patients) or the thoracoabdominal aorta (96 patients), with or without involvement of the aortic arch, and the risk of ischemic injury to the spinal cord and the abdominal organs was judged to be increased. The thoracoabdominal aneurysms were classified using the scheme of Crawford and colleagues [8]. During the study interval, patients with aortic disease confined to localized segments of the descending thoracic aorta (usually in the middle third or the upper third) and those with Crawford type IV aneurysms (aneurysms confined to the infradiaphragmatic aorta) were treated using alternative techniques. No patient with a Crawford type I, II, or III aneurysm was treated by any other technique. Operative Technique The general technique has been described previously [1]. With increasing experience, several modifications have been introduced. After induction of anesthesia and placement of monitoring catheters and a double-lumen endotracheal tube, the descending thoracic aorta is exposed using a posterolateral thoracotomy through the bed of the unresected fifth or sixth rib. When necessary, the incision is extended obliquely across the costal margin toward the midline of the abdomen below the umbilicus. The diaphragm is incised radially or circumferentially. Simultaneously, the left common femoral artery and vein are exposed through an oblique incision in the groin crease. Heparin sodium (3 mg/kg) is administered, and a 28F, 30F, or 32F long cannula is inserted into the Table 2. Extent of Aortic Replacement Extent No. of Patients Aortic Disease Dissection Other Aortic arch and proximal DTA Aortic arch and entire DTA Most or all of DTA Thoracoabdominal aorta Crawford type I Crawford type II Crawford type III Total DTA descending thoracic aorta.

3 Ann Thorac Surg KOUCHOUKOS ET AL 2001;72: HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 701 femoral vein over a guidewire system and positioned in the center of the right atrium. Transesophageal echocardiography is used to facilitate proper placement. With cannulas of these sizes and use of vacuum-assisted venous drainage, flows of 2.0 to 2.4 L min 1 m 2 can be achieved consistently, and cannulation of the pulmonary artery is not necessary. Unless there is severe atherosclerosis of the common femoral or external iliac artery or unless an abdominal aortic aneurysm that contains substantial thrombus is present, the femoral artery is cannulated with a 20F or 22F cannula. This was possible in 153 of the 161 patients. The descending thoracic aorta was used as the site of cannulation in 4 patients. In 2 patients with type B aortic dissection, femoral artery cannulation was discontinued because of malperfusion. In these patients, the arterial cannula was inserted into the aortic arch proximal to the site of resection. Left axillary artery cannulation was required in 1 patient with a large false aneurysm that developed after patch repair of coarctation of the aorta. In another patient, the apex of the left ventricle was cannulated with a long cannula that was passed into the ascending aorta with the aid of transesophageal echocardiography. This patient had moderate aortic regurgitation and required urgent operation for an expanding false aneurysm that occurred after placement of a bypass graft for repair of coarctation of the aorta. Marked left ventricular distention developed after the heart fibrillated. Cardiopulmonary bypass is established immediately after the chest is entered and perfusion cooling is initiated. Methylprednisolone (7 mg/kg) and sodium thiopental (10 to 15 mg/kg) are administered for protection of the central nervous system. During the period of cooling, the abdominal portion of the incision is completed, if indicated. The left lung is collapsed and is gently retracted to minimize manipulation and injury. When the heart fibrillates, a venting catheter is inserted into the left atrium through the left inferior pulmonary vein for decompression. If the vein is not accessible, the vent is placed through the left ventricle near the apex. The aorta proximal to the diseased segment is not clamped, and no form of cardioplegia is used. Cooling is continued until the nasopharyngeal temperature reaches 11 C to 16 C and the bladder temperature reaches at least 22 C. The head is packed in ice. Electroencephalographic monitoring is used, and circulatory arrest is not established until the electroencephalogram becomes isoelectric. Monitoring of somatosensory or motor evoked potentials and cerebrospinal fluid drainage were not used in any patient. When circulatory arrest is required (it was used in 153 of the 161 patients), it is established after the patient is placed in the head-down position. The venting catheter is occluded to prevent suction of air into the heart. For operations confined to the distal aortic arch and proximal descending aorta, resection of the aorta and graft replacement are performed during a single period of circulatory arrest. The aorta distal to the diseased segment is clamped to minimize blood loss. After the anastomosis of the proximal aorta to the graft is completed, cold (15 C), oxygenated blood is perfused retrogradely into the venous cannula to facilitate the evacuation of air and debris from the upper circulation. This is continued at a flow rate that does not elevate the central venous pressure higher than 25 to 30 mm Hg until the graft is filled with blood 4 to 5 cm above the suture line. The graft is then occluded with a clamp adjacent to the suture line, and the retrograde venous perfusion is discontinued. The distal graft aorta anastomosis is then performed, and as it is being completed, the distal aortic clamp is removed and perfusion through the femoral artery cannula, resumed. This maneuver permits removal of debris from the distal aorta and evacuation of air from the graft. After the suture line is completed, residual air is evacuated from the graft with an 18-gauge needle, the proximal clamp on the graft is removed, cardiopulmonary bypass is reestablished, and rewarming is initiated. Cardiopulmonary bypass is discontinued when the bladder temperature reaches 36 C. For procedures that require resection of all or of the distal two thirds of the descending thoracic aorta and part or all of the abdominal aorta, circulatory arrest is established, the aorta distal to the diseased segment is occluded, and the proximal aorta is transected at the appropriate level. If a clamp cannot be placed safely on the distal aorta, it is occluded with a balloon catheter. Sequential clamping of the aorta is not used. After completion of the anastomosis of the aortic graft to the proximal aorta, an aortic perfusion cannula or a 10-mm polyester graft connected to a second arterial line from the pump-oxygenator is attached to the aortic graft adjacent to the anastomosis. With the head of the patient in a head-down position, cold blood is infused through the venous line until all air is evacuated from the brachiocephalic vessels and the aortic arch. Flow through the lower arterial cannula is also initiated. The aortic graft is occluded with a clamp just distal to the proximal arterial line, and flow into the upper aorta is established. If the time of circulatory arrest is short ( 20 to 25 minutes), it can be extended to allow the aorta to be opened to clearly identify patent intercostal and lumbar arteries and the visceral and renal arteries that will be attached to the graft. Flow through the upper and lower circuits is then established. Thirty-five percent of the total arterial flow is directed through the proximal arterial line and 65%, through the distal line. The temperature of the perfusate is adjusted to maintain the nasopharyngeal temperature between 18 C and 20 C, and total flow is maintained between 750 ml to 1.5 L min 1 m 2. During the period of hypothermic low flow, the anastomoses between the aortic graft and the aortic tissue surrounding the lower intercostal, lumbar, visceral, and renal arteries are completed. An attempt is made to attach all patent intercostal and lumbar arteries below the level of the sixth intercostal space to the aortic graft. These arteries were attached in 86 (63%) of the 136 patients who had extensive aortic resections. Direct perfusion of the intercostal, lumbar, renal, or visceral arteries was not used in any patient.

4 702 KOUCHOUKOS ET AL Ann Thorac Surg HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 2001;72: Table 3. Cardiopulmonary Bypass Data Variable Mean a Range Time (min) Cardiopulmonary bypass Cooling Circulatory arrest b Low-flow hypothermic bypass c Hypothermic ventricular fibrillation Spinal cord ischemia Rewarming Temperature ( C) Lowest nasopharyngeal Lowest bladder/rectal a Data are shown as the mean the standard deviation. b Circulatory arrest was not used in 8 patients. c Low-flow hypothermic bypass after an interval of circulatory arrest was not used in 62 patients. Whenever possible, the proximal clamp is repositioned on the graft below the intercostal artery graft anastomoses before the anastomoses to the visceral and renal arteries are completed. Rewarming is initiated after perfusion of the implanted intercostal arteries is established. The heart spontaneously fibrillates during the period of cooling and becomes quiescent. During rewarming, spontaneous defibrillation occurs in most patients when the nasopharyngeal temperature reaches 26 C to 28 C. The venting catheter is then removed. Cardiopulmonary bypass is discontinued when the bladder temperature reaches 36 C. Variables related to cardiopulmonary bypass are shown in Table 3. The duration of spinal cord ischemia was defined as the time between the onset of circulatory arrest or aortic clamping and the resumption of flow to the intercostal arteries below the sixth intercostal space. Statistical Methods Variables examined as potential risk factors and correlates of various events and outcomes are shown in the Appendix. Bivariate contingency tables of discreet variables, logistic transformation and trend analysis of ordinal variables, and t testing of continuous variables were used to explore the relation of an organized set of potential risk factors to each binary (yes/no) outcome variable. Transformations were employed to assure calibration to the assumptions of models. Because of the relatively small size of the data set and the number of events, multivariate analysis was conducted by bootstrap bagging [9]. This involved resampling the original data set 1,000 times to obtain samples of size 75% to avoid low-frequency outlier factors. Automated stepwise regression was then used with a p value of entry of 0.07 and a p value of retention of The variables occurring most often were selected in a multivariate analysis of the original data set, and those still significant at the 0.05 level were retained. Results Mortality The 30-day mortality rate was 6.2% (10 patients) (70% confidence limits, 4.3% to 8.8%) and was identical to the hospital mortality (Table 4). Four patients died intraoperatively of myocardial failure. Two of them had Crawford type II degenerative disease with aortic rupture, 1 had Crawford type I disease with acute type B dissection, and 1 with Marfan s syndrome had Crawford type III disease and had undergone four previous operations on the thoracic and abdominal aorta. Two of the other 6 patients died after a myocardial infarction on the second and 20th postoperative days, and 2 died on the first and third postoperative days of diffuse intravascular coagulopathy and multiple organ system failure that was associated with the administration of aprotinin [10]. One patient died 30 days after successful resection of a ruptured Crawford type II aneurysm of multiple organ system failure after perforation of the colon, which occurred on the tenth postoperative day. One patient died suddenly at home on the 12th postoperative day after an uneventful hospital course. Four of these 6 patients had rupture or acute dissection of the aorta necessitating emergent operation. The most reliably identified risk factor for 30-day mortality was the presence of acute dissection or aortic rupture, which appeared in 84% of the bootstrap samplings (Table 5). The mortality rate was 41% (7 patients) for the 17 patients with one of these conditions and 2.1% (3 patients) for the remaining 144 patients ( p 0.001). The 37 patients with Crawford type II disease also appeared to be at greater risk (16% mortality rate, 6 patients) than the other 124 patients (3.2% mortality rate, 4 patients). However, with bootstrap sampling, the reliability of this as a risk factor was low (34%), in part because of the low frequency of occurrence (see Table 5). Aortic rupture was present in 5 patients with Crawford type II disease, and 4 died. One additional patient died of multiple organ system failure associated with the administration of aprotinin. Among the 31 patients with Craw- Table Day Mortality Rates by Extent of Replacement a Extent of Replacement No. of Patients No. of Deaths 30-Day Mortality % 70% CL Arch and proximal DTA Arch and entire DTA Most or all of DTA Thoracoabdominal aorta Crawford type I Crawford type II Crawford type III Total a Significance: p 0.03, Crawford type II versus Crawford type I, Crawford type III, and all arch and DTA combinations. CL confidence limits; DTA descending thoracic aorta.

5 Ann Thorac Surg KOUCHOUKOS ET AL 2001;72: HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 703 Table 5. Incremental Risk Factors for 30-Day Mortality Variable Logistic Coefficient a p Value Odds Ratio b Frequency of Bootstrap Appearance (%) Acute dissection/rupture (8.0% 272%) 84 Crawford type II disease (1.6% 5.5%) 34 Intercept Goodness of fit (c) a Data are shown the standard deviation. b Numbers in parentheses are 95% confidence limits. ford type II disease without aortic rupture or acute dissection and without administration of aprotinin, the 30-day mortality rate was 3.2% (1 patient). The actual 90-day survival was 88.2% (142 patients). The actuarial 1-year, 3-year, and 5-year survival rates were 85%, 76%, and 63%, respectively. Bleeding and Transfusion Requirements Reoperation for bleeding was required in 8 (5.1%) of the 157 operative survivors. One hundred forty-seven patients (91%) received transfusion of blood products intraoperatively or in the postoperative period. The number of units transfused is shown in Table 6. The duration of cardiopulmonary bypass was the only significant ( p 0.05) incremental risk factor for transfusion. Neurologic Complications Stroke with a resulting focal neurologic deficit occurred in 3 (1.9%) of the 156 operative survivors whose neurologic status could be evaluated. The aorta proximal to the aortic segment that was resected was clamped in 2 of the 3 patients, and both had severe atherosclerotic disease in this area. Those 2 patients were treated in the early period of the study. The proximal aorta is no longer clamped when circulatory arrest is used. The third patient had severe atherosclerosis of the aortic arch and the proximal descending thoracic aorta, which was the likely source of embolization. Using the criteria of Ergin and colleagues [11], transient neurologic dysfunction occurred in 15 (9.6%) of the 156 operative survivors and resolved completely in all. Paraplegia occurred in 4 and paraparesis in 1 of the 156 operative survivors with evaluable neurologic status (3.2%) (70% confidence limits, 1.4% to 6.2%). The neurologic deficit was apparent in 4 of the patients immediately after they awakened and was delayed in 1 patient. That patient had normal neurologic function after emergent operation for a ruptured Crawford type II aneurysm. She had had a previous left colon resection for diverticular disease, and a perforation of the colon associated with hypotension developed on the tenth postoperative day. She became paraplegic after an operation to remove the infarcted colon and died on the 30th postoperative day of sepsis and multiple organ system failure. The patient with paraparesis is ambulatory with residual weakness of the flexor muscles of the hip. The prevalence of spinal cord ischemic injury according to the extent of aorta replaced is shown in Table 7. None of the 65 patients who had resection of the aortic arch and the proximal descending thoracic aorta or all or most of the descending thoracic aorta had development of paraplegia. Among the 91 operative survivors with thoracoabdominal aortic disease, paraplegia occurred in 1 (3.0%) of 33 patients with Crawford type I disease, 1 (2.9%) of 34 with type II disease, and 2 (8.3%) of 24 with type III disease. None of the 50 patients in the entire series with aortic dissection experienced paraplegia or paraparesis. No association was demonstrated between Table 6. Blood Component Transfusion Requirements a Blood Component No. of Patients Given Transfusion No. of Units Mean Median Minimum Maximum Intraoperative (n 161) Red blood cells 133 (83) Fresh frozen plasma 129 (80) Platelets 128 (80) Cryoprecipitate 27 (17) Postoperative (n 157) b Red blood cells 81 (52) Fresh frozen plasma 51 (33) Platelets 32 (20) a Numbers in parentheses are percentages. b This is the number of operative survivors.

6 704 KOUCHOUKOS ET AL Ann Thorac Surg HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 2001;72: the 3 received aprotinin. The fourth patient had complete recovery of renal function. Fig 1. Risk of paraplegia or paraparesis by duration of spinal cord ischemia. Broken lines represent the 70% confidence limits. The p value for the relationship between these two variables (risk of event and duration of ischemia) is the duration of spinal cord ischemia and the development of paraplegia or paraparesis ( p 0.98) (Fig 1). In a multivariate analysis, no incremental risk factors for the development of spinal cord ischemia were identified. Renal Dysfunction Nineteen patients (12%) had a preoperative serum creatinine level higher than 1.5 mg/dl. One of these patients died intraoperatively. In none of the remaining 18 patients did renal failure requiring dialysis develop. Postoperative renal dysfunction was defined as a creatinine level of 1.5 times the preoperative level or higher. Of the last 85 consecutive patients who had multiple determinations of serum creatinine levels in the postoperative period, 30 (35%) had renal dysfunction. Three of these patients required dialysis. None of the remaining 55 patients required dialysis ( p 0.025). Seven patients had only one functioning kidney at the time of operation; none of the 6 patients who survived the operation had development of renal dysfunction. Of the 157 operative survivors, 4 (2.5%) required dialysis. Three of these patients died in the early postoperative period, and 2 of Table 7. Prevalence of Spinal Cord Ischemic Injury Extent of Aortic Replacement No. of Patients a Paraplegia Paraparesis % Arch and proximal DTA Arch and entire DTA Most or all of DTA Thoracoabdominal aorta Crawford type I Crawford type II Crawford type III Total a These were operative survivors whose neurologic function could be evaluated. DTA descending thoracic aorta. Pulmonary Dysfunction Prolonged ( 48 hours) mechanical ventilation was required in 31 (20%) of the 157 operative survivors. It was necessary in 10 (21%) of the 48 patients with preoperative chronic obstructive lung disease and in 21 (19%) of the remaining 109 patients ( p 0.96). The significant incremental risk factors for prolonged mechanical ventilation were older age at operation and use of aprotinin. Five of the 7 patients who received aprotinin and who were operative survivors experienced respiratory failure. No clear association between the extent of aortic disease and the need of prolonged mechanical ventilation was evident. Tracheostomy was required in 13 patients (8%). Of the patients with chronic obstructive lung disease, 8 (17%) required tracheostomy, and of those without such disease, tracheostomy was necessary in 5 patients (4.6%) ( p 0.03). Other Morbidity Of the 157 operative survivors, 17 (11%) required inotropic support for more than 48 hours, 10 (6.4%) sustained gastrointestinal complications (upper gastrointestinal bleeding or bowel resection), 9 (6%) had development of deep venous thrombosis, 7 (4%) sustained wound complications (four deep and three superficial), and 7 (4%) had development of sepsis. The median length of stay in the intensive care unit was 4 days with the longest stay being 48 days. Seventy-five percent of the patients had stays in the intensive care unit of 6 days or less. The median postoperative length of stay in the hospital was 10 days, and the longest stay was 69 days. Comment A number of experimental and clinical studies have demonstrated the protective effect of distal aortic perfusion on spinal cord function. Several techniques involving distal perfusion, such as left heart bypass with permissive hypothermia, and total cardiopulmonary bypass with mild (30 C to 32 C) hypothermia, are widely used [12]. These techniques often include sequential aortic clamping, selective perfusion of the renal and visceral arteries, and other adjuncts such as cerebrospinal fluid drainage and monitoring of somatosensory and motor evoked potentials. Simple aortic clamping with permissive hypothermia or with regional hypothermia of the spinal cord induced by epidural cooling, and with or without the use of other adjuncts, continues to be used by some groups [13, 14]. We [1] believe that hypothermic total cardiopulmonary bypass, usually in combination with a period of circulatory arrest, offers certain advantages over the techniques just mentioned. When the aortic disease involves the distal aortic arch as well as the descending thoracic aorta, or when the distal aortic arch cannot be safely clamped because of severe atherosclerosis or aortic disease that renders this area inaccessible, this technique may be the

7 Ann Thorac Surg KOUCHOUKOS ET AL 2001;72: HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 705 only suitable option. Among the 25 patients in our series who met these criteria, there was no early mortality or major morbidity. The technique is also advantageous with more extensive procedures where the risk of spinal cord ischemic injury can be substantial. The protective effect of hypothermia on spinal cord function after an ischemic interval induced by aortic clamping has been demonstrated experimentally and in clinical studies [1 3, 15]. In the present series, duration of aortic clamping, duration of spinal cord ischemia, and extent of aorta replaced were not identified as risk factors for the development of paraplegia or paraparesis. There was no significant relationship between the occurrence of paraplegia or paraparesis and the duration of spinal cord ischemia, which extended to 138 minutes (see Fig 1). To our knowledge, this is the only technique in which an absence of correlation between these two variables over this extensive time interval has been demonstrated. The recent experience with distal perfusion using atriofemoral bypass or with epidural cooling continues to show a time-related increase in the prevalence of spinal cord ischemic injury with ischemic times greater than 40 to 60 minutes [14, 16, 17]. In our series, paraplegia or paraparesis occurred in 3.0% of the patients with Crawford type I and 2.9% of the patients with type II aortic disease. This low prevalence of spinal cord ischemic injury in these traditionally highrisk subgroups does not exceed and appears to be lower than that recently reported for the other currently used techniques [14, 16 19]. The role of preservation and reattachment of lower intercostal and lumbar arteries in reducing the prevalence of spinal cord ischemic injury after operations on the thoracoabdominal aorta is not clearly established. However, there appears to be consensus that reattachment of these arteries should be attempted whenever possible to reduce the probability of spinal cord ischemic injury. Hypothermia increases the tolerable duration of spinal cord ischemia and provides a longer safe interval for implantation of these arteries into the aortic graft. In the present study, aortic rupture or acute dissection requiring emergent operation and the presence of Crawford type II disease were incremental risk factors for 30-day mortality. Emergent operation for aortic rupture or dissection has been shown to be an important predictor of hospital mortality with all of the currently used techniques and particularly in patients with Crawford type II disease [5, 18, 20 22]. For elective operations, the 30-day mortality rate in the present series was 2.1% and it was 3.2% among the patients with Crawford type II disease when the patients in whom aprotinin was used were excluded. These mortality rates do not exceed those reported with the other currently used techniques [14, 16 19, 23, 24] and are comparable to those in other recently reported series in which cardiopulmonary bypass and deep hypothermia were used [2, 3]. Hypothermia also provided substantial protection of the kidneys without the need of direct perfusion or other adjuncts during the period of aortic clamping. Only 4 (2.5%) of the 157 operative survivors required dialysis. None of the 18 patients with an elevated serum creatinine level preoperatively who survived the operative procedure had development of renal failure that required dialysis. Because of variation in the criteria that have been used to define postoperative renal failure, comparison of our results with other series is difficult. However, if need of postoperative renal dialysis is used as an end point, then the prevalence of renal failure is lower than that reported for simple aortic clamping for extensive descending thoracic and thoracoabdominal aneurysms and for techniques using normothermic or mildly hypothermic distal perfusion, often in combination with direct renal perfusion [18, 23 26]. In studies employing simple aortic clamping or normothermic distal perfusion, preoperative renal dysfunction was observed to be a predictor of postoperative renal failure [25, 26]. This relationship was not observed in the present series. Systematic assessment of abdominal organ system function was not performed in our study. Other reports [26 29] have demonstrated the deleterious effects of supraceliac aortic clamping on hepatic and pulmonary function and on the coagulation system, and its association with the development of multiple organ system dysfunction. Although selective perfusion of the visceral and renal arteries during clamping of the aorta above the celiac artery may reduce the frequency and the severity of the ischemia-reperfusion injury to these organs, injury to the arteries by the balloon-tipped perfusion catheters, insufficient flow, high shear rates, absence of pulsatile flow, and inability to insert catheters because of occlusive disease may limit its effectiveness [30]. The use of profound hypothermic cardiopulmonary bypass obviates the need to clamp the supraceliac aorta and selectively perfuse the visceral arteries, and appears to provide adequate protection of the liver and the other abdominal organs. With the exception of 2 patients who died early postoperatively of diffuse intravascular coagulopathy associated with the use of aprotinin, multiple system organ failure occurred in only 1 patient in our series and developed as a consequence of a perforation of the colon. Lack of a standard method for reporting pulmonary complications after extensive resections of the thoracic and thoracoabdominal aorta makes comparison with other techniques difficult. However, in our series, the prevalence of major pulmonary complications (prolonged mechanical ventilation and need of tracheostomy) does not differ appreciably from that reported in other series involving the descending thoracic and thoracoabdominal aorta in which simple aortic clamping or distal perfusion techniques were used [22 24, 27, 31]. This suggests that other factors besides the use of hypothermic cardiopulmonary bypass and circulatory arrest are responsible for these complications. Cardiac complications occurred infrequently in our series and were related primarily to coexisting coronary artery disease. Hypothermic fibrillation and appropriate venting provided adequate myocardial protection. Concern about excessive blood loss as well as increased mortality and pulmonary complications has led to skepticism regarding the value of this technique in the

8 706 KOUCHOUKOS ET AL Ann Thorac Surg HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 2001;72: management of patients with extensive thoracic aortic disease that requires a lateral approach [4 6]. The technique has often been reserved for desperate situations in which no alternative method is feasible [4, 5]. Little information on the utilization of blood products with the other currently used techniques is available. In a series of 198 patients with descending thoracic aneurysms reported by Coselli and colleagues [23] in which simple aortic clamping with minimal hypothermia and low-dose heparin was the predominant technique employed, the mean number of units of red blood cells, fresh frozen plasma, platelets, and cryoprecipitate exceeded those required in the present series. In a study of patients with thoracoabdominal aneurysms by Leijdekkers and associates [30], the transfusion requirements were significantly higher in patients in whom visceral perfusion was used in conjunction with distal bypass than in patients in whom only distal perfusion was used. The detrimental effects of hypothermia and circulatory arrest on platelets and coagulation factors may be offset by the protective effect of hypothermia on visceral organ function and a blunting of the coagulopathy that can be induced by visceral ischemia [28, 32]. This protection can be achieved without direct perfusion of the visceral arteries. In conclusion, our extended experience with hypothermic cardiopulmonary bypass and circulatory arrest confirms the safety and efficacy of the technique for operations on the distal aortic arch, the descending thoracic aorta, and the thoracoabdominal aorta. This method provides substantial protection against paralysis and against renal, cardiac, brain, and visceral organ system dysfunction that equals or exceeds that provided by other currently used techniques. Hypothermia substantially increases the tolerable duration of spinal cord ischemia, thus allowing a safe interval for attachment of intercostal and lumbar arteries, and provides satisfactory protection of the kidneys and abdominal viscera without the need of other adjuncts. We believe that continued use of this technique for the management of extensive aortic disease that requires lateral thoracic or thoracoabdominal exposure is justified. Addendum Since this manuscript was submitted for publication, this technique has been used in an additional 11 patients (5 with involvement of the descending thoracic aorta and 6, the thoracoabdominal aorta [1 with Crawford type I and 5 with Crawford type II disease]). There have been no early deaths, and no patient has had development of paraplegia, paraparesis, or renal failure requiring dialysis. We thank Dr Robert Forstat, Dr Kevin Bucol, Dr Leander Lee, Timothy Burns, John Brooks, Jeanne Rhoades, Robert Nowak, and Brian Lowery for superb anesthesia management and cardiopulmonary perfusion. References 1. Kouchoukos NT, Daily BB, Rokkas CK, Murphy SF, Bauer S, Abboud N. Hypothermic bypass and ciruclatory arrest for operations on the descending thoracic and thoracoabdominal aorta. Ann Thorac Surg 1995;60: Okita Y, Takamoto S, Ando M, et al. Repair for aneurysms of the entire descending thoracic aorta or thoracoabdominal aorta using a deep hypothermia. Eur J Cardiothorac Surg 1997;12: Carrel TP, Berdat PA, Robe J, et al. Outcome of thoracoabdominal aortic operations using deep hypothermia and distal exsanguination. Ann Thorac Surg 2000;69: Crawford ES, Coselli JS, Safi HJ. Partial cardiopulmonary bypass, hypothermic circulatory arrest, and posterolateral exposure for thoracic aortic aneurysm operation. J Thorac Cardiovasc Surg 1987;94: Safi HJ, Miller CC 3rd, Subramaniam MH, et al. Thoracic and thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass, profound hypothermia, and circulatory arrest via left side of the chest incision. J Vasc Surg 1998;28: Cambria RP, Davison JK, Zannetti S, et al. Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair. J Vasc Surg 1997;25: The Society of Thoracic Surgeons National Database. Definitions of terms of The Society of Thoracic Surgeons National Database. Chicago, IL: The Society of Thoracic Surgeons, Crawford ES, Crawford JL, Safi HJ, et al. Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long-term results of operations in 605 patients. J Vasc Surg 1986;3: Breiman L. Bagging predictors. Machine learning 1996;26: Sundt TM III, Kouchoukos NT, Saffitz JE, Murphy SF, Wareing TH, Stahl DJ. Renal dysfunction and intravascular coagulation with aprotinin and hypothermic circulatory arrest. Ann Thorac Surg 1993;55: 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: Kouchoukos NT, Dougenis D. Surgery of the thoracic aorta. N Engl J Med 1997;336: Acher CW, Wynn MM, Hoch JR, Popic C, Archibald J, Turnipseed WD. Combined use of cerebral spinal fluid drainage and naloxone reduces the risk of paraplegia in thoracoabdominal aneurysm repair. J Vasc Surg 1994;19: Cambria RP, Davison JK, Carter C, et al. Epidural cooling for spinal cord protection during thoracoabdominal aneurysm repair: a five-year experience. J Vasc Surg 2000;31: Rokkas CK, Sundaresan S, Shuman TA, et al. Profound systemic hypothermia protects the spinal cord in a primate model of spinal cord ischemia. J Thorac Cardiovasc Surg 1993;106: Safi HJ, Hess KR, Randel M, et al. Cerebrospinal fluid drainage and distal aortic perfusion: reducing neurologic complications in repair of thoracoabdominal aortic aneurysm types I and II. J Vasc Surg 1996;23: Svensson LG, Hess KR, D Agostino RS, et al. Reduction of neurologic injury after high-risk thoracoabdominal aortic operation. Ann Thorac Surg 1998;66: Schepens MAAM, Vermeulen FEE, Morshuis WJ, et al. Impact of left heart bypass on the results of thoracoabdominal aortic aneurysm repair. Ann Thorac Surg 1999;67: Coselli JS, LeMaire SA. Left heart bypass reduces paraplegia rates after thoracoabdominal aortic aneurysm repair. Ann Thorac Surg 1999;67: Mastroroberto P, Chello M. Emergency thoracoabdominal aortic aneurysm repair: clinical outcome. J Thorac Cardiovasc Surg 1999;118: Velazquez OC, Bavaria JE, Pochettino A, Carpenter JP. Emergency repair of thoracoabdominal aortic aneurysms with immediate presentation. J Vasc Surg 1999;30:

9 Ann Thorac Surg KOUCHOUKOS ET AL 2001;72: HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS Coselli JS, LeMaire SA, Koksoy C, Schmittling ZC. Results of thoracoabdominal aortic aneurysm repair with acute presentation. J Thorac Cardiovasc Surg 2001; in press. 23. Coselli JS, Plestis KA, La Francesca S, Cohen S. Results of contemporary surgical treatment of descending thoracic aortic aneurysms: experience in 198 patients. Ann Vasc Surg 1996;10: Martin GH, O Hara PJ, Hertzer NR, et al. Surgical repair of aneurysms involving the suprarenal, visceral, and lower thoracic aortic segments: early results and late outcome. J Vasc Surg 2000;31: Kashyap VS, Cambria RP, Davison JK, L Italien GJ. Renal failure after thoracoabdominal aortic surgery. J Vasc Surg 1997;26: Safi HJ, Harlin SA, Miller CC 3rd, et al. Predictive factors for acute renal failure in thoracic and thoracoabdominal aortic aneurysm surgery. J Vasc Surg 1996;24: Harward TR, Welborm MB 3rd, Martin TD, et al. Visceral ischemia and organ dysfunction after thoracoabdominal aortic aneurysm repair. A clinical and cost analysis. Ann Surg 1996;223: Gertler JP, Cambria RP, Brewster DC, et al. Coagulation changes during thoracoabdominal aneurysm repair. J Vasc Surg 1996;24: Vermeulen EG, Blankensteijn JD, van Urk H. Is organ ischaemia a determinant of the outcome of operations for suprarenal aortic aneurysms? Eur J Surg 1999;165: Leijdekkers VJ, Wirds JW, Vahl AC, et al. The visceral perfusion system and distal bypass during thoracoabdominal aneurysm surgery: an alternative for physiological blood flow? Cardiovasc Surg 1999;7: Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi HJ. Variables predictive of outcome in 832 patients undergoing repairs of the descending thoracic aorta. Chest 1993;104: Illig KA, Green RM, Ouriel K, et al. Primary fibrinolysis during supraceliac aortic clamping. J Vasc Surg 1997;25: Appendix Variables Examined as Possible Risk Factors and Correlates of Outcomes Patient Data Age (y), sex Clinical status New York Heart Association functional class, symptomatic patient (yes/no) Previous procedures (yes/no) Proximal aortic repair, abdominal aortic aneurysm repair, distal aortic repair, aortic valve replacement, coronary artery bypass grafting, coronary angioplasty, coarctation repair Characterization of aortic disease Extent (yes/no) Arch proximal descending thoracic aorta, arch entire descending thoracic aorta, most or all of descending thoracic aorta, thoracoabdominal aorta; Crawford type of thoracoabdominal aneurysm Etiology (yes/no) Degenerative, dissection, other; Marfan s syndrome; coarctation Presentation (yes/no) Unruptured aneurysm, chronic dissection, acute dissection or rupture Anatomy (yes/no) Intercostal and/or lumbar arteries at risk Comorbidity (yes/no) Hypertension, coronary artery disease, chronic obstructive lung disease, peripheral vascular disease, stroke, diabetes, preoperative serum creatinine level (mg/dl) Procedure Reimplantation of intercostal and/or lumbar arteries (yes/no) Support Techniques Use of circulatory arrest (yes/no) and duration (min), use of low-flow bypass (yes/no) and duration (min), duration of cooling (min) and rewarming (min), duration of cardiopulmonary bypass (pump time, min), elapsed time of cardiopulmonary bypass (pump time total circulatory arrest time, min), use of fibrillatory arrest (yes/no) and duration (min), duration of spinal cord ischemia (min), duration of visceral ischemia (min), use of aprotinin (yes/no), aortic clamp duration (min), lowest nasopharyngeal temperature ( C), lowest rectal or bladder temperature ( C). Experience Date of operation (years since January 1, 1986) DISCUSSION DR DENTON A. COOLEY (Houston, TX): Dr Kouchoukos and colleagues deserve accolades for their results using hypothermic circulatory arrest to provide spinal cord protection for a series of 161 patients undergoing resection of aneurysms in this critical area of the thoracic aorta. Spinal cord injury is the most dreaded complication surgeons face in treating these lesions. Hypothermia has become the most effective adjunct for preserving central nervous system tissues, but its application for protecting the spinal cord has not been adequately explored. The disadvantages of hypothermia have been extensively reported and include coagulopathy, pulmonary cold injury, and the so-called whole-body inflammatory response of cardiopulmonary bypass.

10 708 KOUCHOUKOS ET AL Ann Thorac Surg HYPOTHERMIC CIRCULATORY ARREST FOR THORACOABDOMINAL OPERATIONS 2001;72: In attempts to protect the spinal cord, surgeons have used many techniques, either alone or in combination with hypothermia, including circulatory bypass, pharmacologic agents, and spinal fluid pressure modifications. My colleagues and I have used the simple single clampand-go technique with an open distal anastomosis in repair of aneurysms of the descending thoracic aorta and thoracoabdominal aorta in a series of 148 consecutive patients. Clamp time was almost uniformly less than 30 minutes. Neurologic complications, ie, paraplegia or paraparesis, occurred only when the aneurysm was located in or included the distal third of the descending aorta. Twelve patients (8.1%) sustained a neurologic complication. The complication rate in the proximal third of the thoracic aorta was 0%; there were no neurologic complications in that group. In 75 patients with aneurysmal involvement of the distal third, above the celiac axis, there were four complications, and when the entire descending thoracic aorta plus the thoracoabdominal segment was involved, 8 patients sustained some neurologic problems. With the expectation of further reducing neurologic complications, I have begun using atrium distal aorta bypass with a heat exchanger in the circuit. No adjuncts other than spinal fluid drainage will be used. The objective is to induce cold only in the anatomic region of the body in jeopardy of ischemic injury, partially excluding the upper body, a concept of selective hypothermia. Although we are still refining the method for inducing hypothermia and determining the optimum temperature change, in general, I believe a temperature reduction of 10 to 15 is probably suitable without substantially altering upperbody temperature. After circulatory bypass from the left atrium to the distal cannula is begun, the proximal clamp is applied for 15 to 20 minutes to cool the spinal cord before the aneurysm is opened. The distal repair is performed by the open technique, and an autotransfusion device is used to recover blood. We also intend later to use spinal fluid cooling as an adjunct for additional spinal cord protection. Epidural selective cooling of only the spinal cord has been reported by others but does not protect the abdominal viscera. Dr Kouchoukos, please describe how you select patients for hypothermic arrest. Do you use it for all aneurysms? Of course, lesions that involve the arch and cerebrovascular tributaries require the technique, and lesions in the thoracoabdominal region are vulnerable to complications relating both to the spinal cord and to the abdominal viscera. Do you use the same or other techniques for aneurysms confined to the middle or upper third of the aorta? If so, what are they? Do you use this for localized sacciform aneurysms? Does excessive body size affect your selection of technique, as some very large patients may require more than 1 hour of perfusion to restore normothermia. Also, prolonged operating room time may be costly. Is that a consideration? What conclusions have you made about the use of aprotinin with hypothermic arrest? I wonder whether we might find a better or more efficient way to cool only or mostly the spinal cord and viscera. I compliment Dr Kouchoukos and his colleagues on this very excellent presentation. DR SULAIMAN B. HASAN (Charleston, WV): I congratulate Dr Kouchoukos for an excellent presentation. It appeared that most of your patients were cannulated by the femoral route, and yet the stroke rate was low. Do you have any thoughts about that? In the case of large atherosclerotic aneurysms, I have always been concerned about running the arterial perfusate retrograde. How many patients had concomitant coronary artery disease, and how do you deal with it? DR KOUCHOUKOS: Dr Cooley, thank you for your comments. As most of you know, Dr Cooley pioneered the use of hypothermia for spinal cord protection in the mid-1950s, and I am pleased to hear that he is reevaluating it clinically as a method for reducing the incidence of spinal cord ischemic injury. In regard to the selection of patients, no patient with an extensive descending thoracic aortic resection or Crawford type I, II, or III thoracoabdominal disease was treated by any other method during the study interval. Patients with disease confined to the proximal or middle third of the descending thoracic aorta were managed with femoral-femoral bypass using a pumpoxygenator and mild hypothermia. Patients with Crawford type IV disease were managed with simple clamping. We use this technique on all patients who meet our criteria irrespective of size. The mean duration of rewarming was approximately 70 minutes for the entire series. Rewarming is begun as soon as perfusion of the lower intercostal arteries is established. Thus, when the anastomoses to the visceral and renal arteries and to the distal aorta are being performed, we are already rewarming. Therefore, this is not totally wasted time. Because of an unfavorable experience with aprotinin in patients undergoing circulatory arrest early in our study, we no longer use it intraoperatively. It is occasionally administered after cardiopulmonary bypass has been discontinued and protamine sulfate has been administered if there is evidence of increased thrombolytic activity. Although regional cooling of the spinal cord and viscera might be advantageous, we believe that systemic cooling also has advantages because it provides protection for the brain and the myocardium as well. I agree with Dr Cooley that we should be looking for better ways to cool selectively, and the technique he described is one way to approach that problem. Dr Hasan, as for the issue of femoral artery cannulation and stroke, this is a concern for anyone who cannulates the femoral artery in patients with atherosclerotic aortic disease. Two of the three strokes in this series were associated with clamping of the aorta in the presence of severe atherosclerotic disease in the arch. This was early in the experience, and we no longer place clamps in this area. This is the most likely explanation for embolic stroke with use of this technique. We avoid femoral cannulation in patients who have aneurysms in the iliac artery and in those who have large abdominal aneurysms where there is the potential for retrograde embolization of particulate matter. In that situation, we cannulate either the aorta or the axillary artery. Twenty-nine percent of the patients had coronary artery disease. Nineteen percent had had coronary artery bypass grafting or a percutaneous catheter intervention before the aortic operation. We screen patients who are undergoing elective operation for coronary artery disease and treat the disease aggressively before the aortic procedure.