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J Thorac Cardiovasc Surg 1998;115:129-133
© 1998 Mosby, Inc.
SURGERY FOR CONGENITAL HEART DISEASE |
From the Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan. Read at the Seventy-seventh Annual Meeting of The American Association for Thoracic Surgery, Washington, D.C., May 4–7, 1997.
Received for publication May 6, 1997; revisions requested June 17, 1997; revisions received Sept. 29, 1997; accepted for publication Sept. 30, 1997. Address for reprints: Yutaka Okita, MD, Department of Cardiovascular Surgery, National Cardiovascular Center 5–7–1, Fujishirodai, Suita, Osaka 565, Japan.
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Abstract |
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Introduction |
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TopAbstractIntroductionPatients and methodsResultsDiscussionConclusionAppendix: DiscussionReferences |
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1 it is a predominant cause of mortality and morbidity after thoracic aortic surgery because of the growing population of elderly patients undergoing such operations. 2–4 Despite recent progress in surgery for thoracic aortic aneurysm, complications involving the central nervous system are still prevalent, especially in patients with aortic arch aneurysm. 1–4 In 1993, Svensson and associates 5 reported that the occurrence of stroke was observed to increase after 40 minutes of circulatory arrest, and the mortality rate increased markedly after 65 minutes of circulatory arrest. In 1994, Ergin and coworkers 3 reported that the safe limit for circulatory arrest was 60 minutes. However, the retrograde cerebral perfusion (RCP) technique added a new idea that can augment cerebral protection during deep hypothermic circulatory arrest (DHCA). 6 The current study deals with our surgical experience and the postoperative neurologic outcome in 148 patients who underwent aortic arch operations in which DHCA combined with RCP (DHCA + RCP) was used. |
Patients and methods |
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TopAbstractIntroductionPatients and methodsResultsDiscussionConclusionAppendix: DiscussionReferences |
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The chest was entered through a median sternotomy in 92 patients and through a left thoracotomy in 56. Intraoperative echography, direct epiaortic scan, and transesophageal echography were routinely used in every patients to locate a safe site for aortic cannulation and clamping. In 117 patients (79%), 2 million units of aprotinin was added to the pump prime. An arterial cannula was inserted in the ascending aorta in 45 patients and in the femoral artery or descending aorta in 103. Soft aortic cannulas were used to prevent thromboemboli.
Through a median sternotomy, 6 RCP was implemented with the use of the bypass bridge connecting the arterial and venous lines of the extracorporeal circuit to reverse the flow into the superior vena cava cannula after the initiation of total DHCA at a nasopharyngeal temperature of less than 18° C. Continuous RCP flow was necessary to maintain an internal jugular vein pressure of 15 to 20 mm Hg. Blood draining into the aortic arch was aspirated. Cardiopulmonary bypass was instituted through a left thoracotomy with left atrial venting. 7 The descending aorta was clamped proximal to the arterial cannula and the distal aortic arch aneurysm was incised after the patient had been cooled to 18° C. RCP was initiated at a central venous pressure of 15 to 18 mm Hg. Proximal anastomosis of a graft with the distal aortic arch was performed during RCP.
Topical external cooling of the brain with an ice jacket is a prerequisite to maintain cerebral hypothermia. Intracranial content of oxygenated hemoglobin was monitored by means of near-infrared spectroscopy. Clamping of the aortic arch was avoided and an open aortic anastomosis technique was used in all patients. Selective cerebral perfusion was available on standby when the duration of DHCA exceeded 80 minutes; however, it was not necessary. After revascularization of cerebral vessels, antegrade perfusion of the brain was initiated as early as possible. Slow rewarming was preferred.
Operative procedures consisted of replacement from the ascending aorta and proximal aortic arch in 28 patients, total arch replacement in 62, distal arch replacement in 38, simultaneous replacement of the distal arch and the descending aortas or thoracoabdominal aorta in 12, and patch repair of the aneurysms in 8. Thirty concomitant procedures consisted of "elephant trunk" installation in 15 patients, aorta-coronary bypass in 7, Bentall's operation in 3, carotid endarterectomy in 2, remodeling of the aortic root in 2, and graft replacement of the infrarenal abdominal aorta in 1.
Postoperative stroke was defined as a newly developed neurologic deficit, new lesions diagnosed by computed tomography, or unresponsiveness 3 days after the operation. Postoperative delirium was defined as a transient disorientation and character change with no neurologic sequelae.
Univariate statistical analysis was done by 
2 test and Student's t test. Thirty-one perioperative variables that were considered to affect postoperative mortality and morbidity (Table II) were entered for analysis by multivariate logistic regression with stepwise addition of variables. A contingent probability of 0.10 or less was used to enter variables into the logistic models in a forward-stepping manner, and a contingent probability of 0.15 or less was used to remove variables from the model. Postoperative complications were not taken into account as variables in analyzing postoperative brain damage. The estimated relative risk was the likelihood of an event in the presence of a variable compared with its likelihood in the absence of that variable. All statistical significance was assumed at the p < 0.05 level.
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Results |
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TopAbstractIntroductionPatients and methodsResultsDiscussionConclusionAppendix: DiscussionReferences |
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. Significant factors for hospital death by univariate analysis were older age (>70 years), preoperative COPD, ruptured aneurysm, arterial cannulation in the ascending aorta, postoperative stroke, respiratory complication, bleeding, acute renal failure, sepsis, disseminated intravascular coagulation, and gastrointestinal problems (Tables IV and V). Stepwise logistic regression analysis of perioperative variables demonstrated that the significant risk factors for hospital death were ruptured aneurysm, preoperative COPD, arterial cannulation in the ascending aorta, and perioperative stroke (Table VI).
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). Multivariate stepwise logistic regression analysis revealed that risk factors for stroke were ruptured aneurysm and surgery on the distal arch (see ).
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and ).
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Duration of bypass was 187 ± 78 minutes, ranging from 90 to 696 minutes. Duration of the bypass was longer than 180 minutes in 53 patients. Cardiac arrest time was 79 ± 38 minutes, ranging from 22 to 220 minutes, and was more than 120 minutes in 25 patients. Duration of DHCA + RCP was 49 ± 17 minutes, ranging from 21 to 95 minutes, and was more than 60 minutes in 36 patients. Duration of DHCA + RCP did not correlate with incidences of hospital death (p = 0.635), stroke (p = 0.971), or delirium (p = 0.972, Fig. 1).
Patients awoke at a mean of 7.5 ± 8.2 hours (range 1 hour to 49 hours) after the operation. Five patients regained consciousness 24 hours after the operation. Endotracheal extubation was accomplished at 47.1 ± 107.8 hours (range 5 hours to 34 days) after the operation. A delay in extubation (>36 hours after operation) for various reasons occurred in 34 patients. The averaged duration of ICU stay was 6.9 ± 9.8 days, ranging from 1 day to 80 days, and 29 patients had to stay in the ICU 7 days after the operation. Duration of DHCA + RCP did not correlate with length of time before the patient awoke (r = 0.03, p = 0.80), extubation time (r = 0.12, p = 0.92), and ICU (r = 0.11, p = 0.37) or hospital stay (r = 0.05, p = 0.69). The differences in the incidence of mortality (p = 0.39), stroke (p = 0.65), and delirium (p = l.00) were not statistically significant between the two groups of patients (Table XI).
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Discussion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionConclusionAppendix: DiscussionReferences |
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6 used logistic regression analysis to evaluate 656 patients after aortic operations in which DHCA was used. They reported that there were 44 permanent or transient strokes (7%) and that the multivariate determined predictors were a history of cerebrovascular disease, previous aortic surgery distal to the left subclavian artery, and cardiopulmonary bypass time. The occurrence of stroke was observed to increase after 40 minutes of circulatory arrest, and the mortality rate increased markedly after 65 minutes of circulatory arrest. Ergin and associates 3 showed that temporary neurologic dysfunction occurred in 19% of patients and permanent neurologic deficits were seen in 9% of patients who underwent arch operations with DHCA. Strokes occurred in 11% of their patients but were associated with permanent deficits in 6.9%.
Age and the duration of the arrest period were the only determinants for the occurrence of postoperative neurologic dysfunction. A strong correlation between duration of arrest and cerebral injury, especially the rapid rise in the incidence of temporary dysfunction beyond 50 minutes of arrest time, was demonstrated. Using DHCA + RCP, Coselli and associates 8 demonstrated that early mortality was 6.1% and no transient or permanent stroke was detected in 111 patients. Duration of DHCA in their series was less than 40 minutes under condition of electroencephalogram silence. Lytle and associates 9 reported that four hospital deaths, one stroke, and three transient neurologic deficits occurred in 34 patients who had aortic surgery in which DHCA + RCP was used. Periods of DHCA ranged from 4 to 110 minutes (mean 38 minutes) at a bladder temperature of 18° C. For seven patients the period of DHCA was longer than 60 minutes. Lin and associates 10 demonstrated that one of 23 patients died after aortic surgery with DHCA + RCP and no patients had neurologic complications. The DHCA period was 75 ± 12 minutes, ranging from 58 to 104 minutes, at a rectal temperature of 23.3° ± 0.5° C. They also reported that brain cognitive function tests of patients who underwent aortic surgery with DHCA showed no difference compared with a control group 3 months after the operation. In a multicenter study of 228 patients who underwent aortic surgery with DHCA + RCP in 49 institutions in Japan, Usui and associates 11 demonstrated that duration of DHCA was the single predictive factor of a cerebral complication. The incidence of permanent neurologic dysfunction was less than 10% when the DHCA period was shorter than 60 minutes but increased abruptly when this period exceeded 100 minutes, and it remained 15% between 60 and 99 minutes. In the current study, duration of DHCA was 49 ± 17 minutes, ranging from 21 to 95 minutes, and for 36 patients the period of DHCA was longer than 60 minutes. The incidence of hospital death, postoperative stroke, and transient delirium was not correlated to the periods of DHCA. Among six patients with postoperative stroke, only one patient had a stroke as a result of prolonged ischemia and other patients had strokes of a clear embolic origin. We empirically consider that a DHCA + RCP period of up to 80 minutes under a nasopharyngeal temperature of 18° C is safe.
The RCP technique 6 added a new idea that can augment cerebral protection during DHCA, 12 but the actual mechanism by which RCP provides cerebral protection is still obscure. Pagano and associates 13 demonstrated that radioisotope tracers accumulated throughout the white and gray matter of the brain during RCP in human beings. In canine experiments, Watanabe and associates 14 demonstrated that RCP through the sagittal sinus and superior vena cava protected the brain during 90 minutes of DHCA. It is clearly effective in maintaining cerebral hypothermia, providing continuous cooling of the whole head, preventing debris and air from reaching the terminal vessels of the brain, 15,16 and in washing out some metabolites, to delay the onset of acidosis in the ischemic brain. 17
Multiple mechanisms of stroke are speculated as causes, including hypoperfusion or hyperperfusion during or after the operation and embolization from a variety of sources, including the extracorporeal circuit, left side of the heart, aorta itself, iliac artery, or carotid bifurcation. Despite the recent advent of diagnostic modalities, it is often difficult to determine which of these mechanisms are implicated in a particular patient. 18 However, a recent report indicated that the majority of permanent neurologic injuries were due to strokes resulting from embolic phenomena and were not directly related to the method of cerebral protection used. 19
Postoperative transient delirium has been defined as a transient minor neurologic deficit such as disorientation and character change with no neurologic sequelae. However, delirium can result in increased morbidity, delayed functional recovery, and prolonged hospital stay. In a review, Dubin, Field, and Gastfriend 20 concluded that cardiac status, the severity of physical illness, the complexity of the surgical procedure, preoperative anxiety, denial depression, and preoperative organic brain disease were the determining factors in postcardiotomy delirium. Vasquez and Chitwood 21 demonstrated that pathologic brain injuries that were apparently anatomic correlates of neurologic deficits in delirium included anoxic lesions of the hippocampus and infarcted foci. They also showed that contributing physiologic factors included long periods of extracorporeal circulation, arterial hypotension during the operation, emboli, low cardiac output, age, and severity of cardiac dysfunction. In the current study, no significant correlation was demonstrated between incidence of the delirium and type of aortic lesions, duration of cardiopulmonary bypass or DHCA, age, and sex. Usually delirium occurs after patients have left the ICU and continues for a week or so. Prognosis is always benign.
Our main principle for avoiding postoperative stroke focused on not clamping the arch and performing anastomoses in an open manner. Normal aorta for cannulation is carefully evaluated by direct scan echo in every patient. In patients with severe atheromatous disease of the descending aorta, abdominal aortic aneurysm, and occlusive disease in the iliac arteries, RCP from the femoral cannula is avoided. If femoral cannulation is unavoidable, antegrade cardiac output is maintained at least over the first 10 minutes of bypass to prevent debris from the descending or abdominal aorta from reaching the brain. An additional arterial return line is always inserted for pump rewarming by antegrade flow through a side branch of the arch graft. Cerebral embolization cannot be predicted or prevented by electroencephalography, near-infrared oximetry, or monitoring of oxygen saturation of the jugular vein. The brain is cooled topically with ice packs. If intraoperative echography indicates that a nonaneurysmal portion of the arch is coated with thick atheromatous plaque, the whole arch should be replaced without hesitation. Open aortic anastomosis after complete transection of the aorta is the preferred method for secure anastomosis. A quadritruncated Dacron graft is usually chosen for total arch replacement with reconstruction of the arch vessels. Clearing debris from the suture line by flushing with saline solution and cautious handling of the air and debris are extremely important to prevent brain embolism.
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Conclusion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionConclusionAppendix: DiscussionReferences |
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Appendix: Discussion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionConclusionAppendix: DiscussionReferences |
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The prevalence of this severe and prolonged dysfunctional state in this series of patients leaves me wondering how much of this is related to relatively prolonged periods of DHCA at 18° C. RCP apparently did not prevent it. One could argue that it may in fact have compounded the injury by increasing cerebral edema. We know that effective prolonged RCP invariably is associated with cerebral edema. This should raise a caution flag for all who believe that RCP gives one the luxury of time that one would not have with DHCA alone.
We should concentrate on limiting the arrest time rather than relying on prolonged RCP to extend it, because of the increasing potential for harm with RCP. Limiting arrest times to less than 50 minutes is a readily achievable goal in virtually every case if one plans the operation well.
Prevention of embolic strokes is a daunting problem, and RCP may prove to be more useful in solving that. Dr. Okita reported a low 4% incidence of stroke. In our experience, older age, "dirty" aorta, and descending aortic involvement are the major determinants of postoperative stroke. When we use RCP selectively in this high-risk group for prevention of stroke, RCP emerges as a marker for neurologic injury.
Dr. Okita, I notice that you also reported a substantially higher, 2% versus 7%, stroke rate in patients who were operated on through a left thoracotomy. Your difference would also reach statistical significance if you merely double your sample size.
I would argue that the RCP in this high-risk group has not prevented the occurrence of these strokes. Therefore, I would say that the RCP falls short in just the situation in which it may be most useful and necessary. In my opinion, RCP remains a promise yet unfulfilled.
I have three questions. First, when operating through a left thoracotomy, do you use any additional measures to improve the delivery of RCP?
Second, have you taken active measures to prevent, detect, and treat cerebral edema?
Third, how would you reconcile your current results with the multicenter study of RCP in Japan that Dr. Usui presented last year and in which Dr. Takamoto was a participant? They showed a progressively prohibitive increase in risk between 60 and 99 minutes, whereas you show that there is really no risk in extending the RCP beyond 60 minutes.
Dr. Akira T. Kawaguchi (Isehara, Japan). Since you have been assessing injury to the central nervous system by extubation time, occurrence of delirium, and incidence of stroke, I would like to know whether you have any evidence for the preservation of functional and organic and/or morphologic integrity of the central nervous system, in addition to those clinical parameters.
We found that rats undergoing 80 minutes of total circulatory arrest have learning disability (functional damage) and pyramidal cell loss in the hippocampus and cerebral cortex (organic injury) despite prompt recovery of somatic growth, exercise capacity, and normal behavior. Therefore, one cannot exclude possible functional or organic injuries to the central nervous system by assessing such clinical parameters alone.
Dr. Okita. Thank you very much for your nice comments and your questions, Dr. Ergin. When we use a left thoracotomy, we use the near-infrared spectroscopy oxygen monitoring system during the operation. The incidence of stroke or delirium in patients who had a left thoracotomy was not statistically higher than that in patients with median sternotomy. However, this technique inherently includes the risk of allowing debris to enter the arch and ascending aorta. We are very cautious about that.
We use no special techniques to prevent cerebral edema during RCP. We do try to keep the DHCA time as short as possible.
Dr. Usui's article is a multicenter study including more than 50 institutions in Japan. His conclusion was that more than 60 minutes of DHCA is a significant risk factor for brain dysfunction. I do not know why our single-institution data differed from Dr. Usui's results.
Dr. Kawaguchi, thank you for your question. We routinely do preoperative and postoperative computed tomography and electroencephalography to detect lesions for imaging, but we did not find any organic change in the brain. I think something happened in the patient who had postoperative delirium, even though he was well after 1 week or so. A different modality is needed to investigate that.
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K. M. Dossche, W. J. Morshuis, M. A. Schepens, and F. G. Waanders Bilateral antegrade selective cerebral perfusion during surgery on the proximal thoracic aorta Eur. J. Cardiothorac. Surg., April 1, 2000; 17(4): 462 - 467. [Abstract] [Full Text] [PDF]
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N. Shiiya, T. Kunihara, M. Imamura, T. Murashita, Y. Matsui, and K. Yasuda Surgical management of atherosclerotic aortic arch aneurysms using selective cerebral perfusion: 7-year experience in 52 patients Eur. J. Cardiothorac. Surg., March 1, 2000; 17(3): 266 - 271. [Abstract] [Full Text] [PDF]
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 K. Inoue, H. Hosokawa, T. Iwase, M. Sato, Y. Yoshida, K. Ueno, A. Tsubokawa, T. Tanaka, S. Tamaki, and T. Suzuki Aortic Arch Reconstruction by Transluminally Placed Endovascular Branched Stent Graft Circulation, November 9, 1999; 100 (2009): II-316 - II-321. [Abstract] [Full Text] [PDF]
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V. Anttila, K. Kiviluoma, M. Pokela, J. Rimpilainen, M. Makiranta, V. Jantti, J. Hirvonen, and T. Juvonen COLD RETROGRADE CEREBRAL PERFUSION IMPROVES CEREBRAL PROTECTION DURING MODERATE HYPOTHERMIC CIRCULATORY ARREST: A LONG-TERM STUDY IN A PORCINE MODEL J. Thorac. Cardiovasc. Surg., November 1, 1999; 118(5): 938 - 945. [Abstract] [Full Text] [PDF]
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Y. Okita, M. Ando, K. Minatoya, O. Tagusari, S. Kitamura, N. Nakajjma, and S. Takamoto Early and long-term results of surgery for aneurysms of the thoracic aorta in septuagenarians and octogenarians Eur. J. Cardiothorac. Surg., September 1, 1999; 16(3): 317 - 323. [Abstract] [Full Text] [PDF]
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T. Konishi, K. Higuchi, M. Fukata, M. Takeda, S. Akisima, and S. Fukuda Extended aortic replacement in acute dissection by the separated elephant trunk technique Ann. Thorac. Surg., June 1, 1999; 67(6): 1664 - 1668. [Abstract] [Full Text] [PDF]
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Y. Ueda, Y. Okita, S. Aomi, H. Koyanagi, and S. Takamoto Retrograde cerebral perfusion for aortic arch surgery: analysis of risk factors Ann. Thorac. Surg., June 1, 1999; 67(6): 1879 - 1882. [Abstract] [Full Text] [PDF]
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M. A. Ergin, S. Uysal, D. L. Reich, A. Apaydin, S. L. Lansman, J. N. McCullough, and R. B. Griepp Temporary neurological dysfunction after deep hypothermic circulatory arrest: a clinical marker of long-term functional deficit Ann. Thorac. Surg., June 1, 1999; 67(6): 1887 - 1890. [Abstract] [Full Text] [PDF]
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C. H. Wong, S. J. Rooney, and R. S. Bonser S-100{beta} release in hypothermic circulatory arrest and coronary artery surgery Ann. Thorac. Surg., June 1, 1999; 67(6): 1911 - 1914. [Abstract] [Full Text] [PDF]
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S. Westaby, T. Katsumata, and G. Vaccari Arch and descending aortic aneurysms: influence of perfusion technique on neurological outcome Eur. J. Cardiothorac. Surg., February 1, 1999; 15(2): 180 - 185. [Abstract] [Full Text] [PDF]
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Y. Okita, M. Ando, K. Minatoya, S. Kitamura, S. Takamoto, and N. Nakajima Predictive factors for mortality and cerebral complications in arteriosclerotic aneurysm of the aortic arch Ann. Thorac. Surg., January 1, 1999; 67(1): 72 - 78. [Abstract] [Full Text] [PDF]
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