Predictors of Adverse Outcome and Transient Neurological Dysfuntion Following Surgical Treatment of Acute Type A Dissections
Predictors of adverse outcome after replacement of the ascending aorta with resection of the intimal tear and open distal anastomosis were analyzed in 167 patients (109 male, median age 56). Median hypothermic circulatory arrest (HCA) time was 30 minutes (range 12 to 113). Eighty-six patients (pts) had surgery within 24 hours and 81 within 72 hours of symptom onset. Thirty-seven pts had only ascending aortic replacement, 128 had hemiarch repair, and in 2 the entire arch was replaced. The aortic valve was replaced in 37 pts, resuspended in 116, and untouched in 14. Either death or permanent neurological dysfunction was considered an adverse outcome (AO). AO occurred in 30.5% (51/167) of patients overall. Multivariate analysis revealed that the only significant (P<0.05) independent preoperative predictor of AO was hemodynamic instability (OR 6.0). Transient neurological dysfunction (TND) occurred in 19 of 116 patients (16.4%). Significant predictors of TND were increasing age >60 (OR 3.4 and 7.0 in the second and third tertile as compared with the lowest tertile) and coronary heart disease (OR 3.4). Cumulative survival of patients (median follow-up 34 months) was 55% at 1, 49% at 5, and 44% at 8 years, indicating an excessive in-hospital mortality, but excellent long term outcome. Surgical treatment of acute type A dissections is still associated with a high incidence of adverse outcome, but results in excellent long-term survival. Earlier diagnosis, before the development of cardiac tamponade and hemodynamic compromise, is critical to improve the operative salvage rate.
Acute type A aortic dissection, represents an emergency situation that requires immediate surgical intervention to prevent mortality from intrapericardial hemorrhage. Surgical therapy consists mainly in replacing the ascending aorta, regardless of the extent of the pathologic process. Acute aortic insufficiency, when present, is generally treated by valve resuspension or replacement.
Mortality rates from these operations have dramatically improved because of recent advances in preoperative recognition, intraoperative techniques, and postoperative surveillance.1–6 Nevertheless, operations for acute type A dissections are still associated with high mortality rates, often related to preoperative compromise necessitating emergency operation, and perioperative complications.
The current study was undertaken to examine both preoperative and procedural predictors of adverse outcome after operations on the ascending aorta with an open distal anastomosis during a period of hypothermic circulatory arrest (HCA). Adverse outcome was defined as either death or permanent neurological disability, since a successful operation should result not only in survival, but a good quality of life. For most patients, the recitation of a series of separate estimates of the risk of various complications and of mortality is relatively meaningless: what they want to know are the odds that they will emerge from the operation more or less as they were before, but without aneurysm-related symptoms or the threat of imminent aortic rupture.
We also examined factors affecting the incidence of temporary neurological dysfunction because this assessment seems to reflect the adequacy of cerebral protection, and therefore can help in determining how further to improve cerebral recovery following aortic surgery.7
Materials and Methods
The prospective aortic dissection registry database of our institution was interrogated to identify all patients who were operated on acute type A aortic dissection during the study period from 1987 to 2001. Data were collected prospectively for our aortic dissection registry database according to a standard protocol including the evaluation of baseline variables, peri-operative factors and postoperative outcome. In particular, mandatory postoperative neurological examinations are recorded in all patients operated for type A dissections at our institution.
There were 109 men and 58 women whose ages ranged from 16 to 87 years (mean 57±15 years); Sixty-nine patients (41%) were older than 60 years at the time of surgery. Of the entire cohort, 81 patients (48.5%) were operated on urgently (within 72 hours after onset of symptoms), and 51.5% on an emergent basis (within 24 hours after onset of symptoms). Only 11 patients in this series had Marfan’s syndrome.
As seen in Table 1, a history of hypertension was the most common preoperative finding, and there was also a relatively high proportion of patients who had preoperative pulmonary dysfunction and coronary heart disease. In addition, almost half of the patients experienced rupture, had a contained hematoma, and had aortic regurgitation, as shown in Table 2.
All patients had replacement of the ascending aorta with an open distal anastomosis during an interval of hypothermic circulatory arrest. In patients with cardiac tamponade, the left femoral vein was used for venous access. The extent of operation was variable: the site of the tear was resected whenever possible. All patients received low dose aprotinin (1×106 KIU). The surgical technique and the application of profound HCA throughout the study period were standard: the implementation of HCA has previously been described in detail.8 Briefly, it consists of core cooling during cardiopulmonary bypass to an average core temperature of 12° to 15°C measured in the esophagus. The part of the procedure that requires interruption of cerebral blood flow is then done during the period of circulatory arrest. The head is packed in ice to prevent warming of the central nervous system during prolonged circulatory arrest. In patients where retrograde cerebral perfusion was implemented (98 patients) during the period of PHCA, a bypass bridge connecting the arterial and venous lines of the extracorporeal circuit was used to reverse the flow into the superior vena cava cannula. RCP flow rates were adjusted to maintain a mean central venous pressure of 20 mm Hg.
Thirty-seven patients (22.1%) had only ascending aorta replacement; 128 (76.6%) had a hemiarch replacement and 2 patients had ascending aorta plus total arch replacement. The aortic valve was replaced in 43 patients (25.7%). In 104 patients (62.3%) the aortic valve could be resuspended, and it remained untouched in 20 patients (12%). Coronary bypass grafting was the most common concomitant procedure and was performed in 17 patients (10.2%) overall. Other additional procedures such as mitral valve replacement were done in 6.6% of the patients.
Table 3 shows important intraoperative variables. Median circulatory arrest time (HCA) in this series was 30 minutes (range, 11 to 113). Circulatory arrest time was kept below 40 minutes in 73% of all patients: only 45 patients had HCA intervals exceeding 40 minutes.
Assessment of Neurological Complications
The presence of neurological dysfunction at the time of discharge from the hospital, whether focal injury (stroke) or global (coma), was considered permanent neurological injury. Temporary neurological dysfunction, which could only be assessed on operative survivors without permanent neurological dysfunction, was defined as the occurrence of postoperative confusion, transient motor weakness, seizure, agitation, or transient delirium. Computed tomography (CT), when performed on patients with temporary dysfunction, was usually normal.
Continuous data are given as the median and interquartile range (range from the 25th to the 75th percentile) or as the mean and standard deviation (SD), as appropriate. Counts and percentages are given for discrete data. All pertinent risk factors for operative or hospital mortality were examined by chi-square tests, or by Mann Whitney U tests, as appropriate. The univariate analysis was followed by stepwise logistic regression to determine independent risk factors for poor outcome and adjust for confounding factors. Variables that were imbalanced between patients with and without poor outcome as indicated by a probability value of <0.2 were considered for the multivariate analysis. We used a hierachical modeling strategy: preoperative factors were entered first. Those that were significant or significantly added to the model fit were retained in the model and intraoperative factors were then entered. Log likelihood ratio tests, multiplicative interaction terms and the Hosmer Lemeshow test were used to test for interactions between the variables and assess the goodness of fit of the multivariate model. The logit assumption was checked for continuous variables, otherwise continuous variables were categorized into tertiles. The Kaplan Meier method was used to estimate long-term survival rates for all patients. A two tailed probability value of <0.05 was considered statistically significant. Calculations were performed using SPSS for Windows (Version 10.0).
Adverse outcome—death or permanent neurological deficit—occurred in 51 out of 167 patients overall (30.5%). There was no difference in adverse outcome in patients operated urgently (25/51), than in emergency procedures (26/51). Adverse outcome, however, was significantly lower in patients in whom only the ascending aorta or hemiarch was replaced than in those with resection including the total arch (29.7% versus 50%, P=0.03, Table 4B).
Variables that were considered as possible risk factors for an adverse outcome are presented in Tables 4A and 4⇑B. Univariate analysis of the group as a whole revealed a number of preoperative, intraoperative and immediate postoperative factors, which were associated with adverse outcome, Tables 4A and 4⇑B. The preoperative risk factors were: preoperative pulmonary dysfunction, previous aortic surgery and hemodynamic compromise.
Among the intraoperative factors predicting a poor outcome in the group as a whole, only extent of resection emerged as a statistically significant factor.
The location of the intimal tear, duration of HCA, use of retrograde cerebral perfusion, whether the aortic valve was untouched, replaced or resuspended all failed to show any impact on hospital mortality.
Multivariate analysis revealed that the only statistically significant independent preoperative predictor of adverse outcome was hemodynamic instability (Table 5).
Transient Neurological Dysfunction
Transient neurological dysfunction, which was evaluated only in patients surviving operation without permanent neurological dysfunction, occurred in 19 of 116 patients (16.4%).
Variables that were considered as possible risk factors for transient neurological dysfunction are presented in Tables 6A and 6⇓B. Univariate analysis showed that none of the preoperative factors, which were important contributors to adverse outcome, were also implicated in the occurrence of transient neurological dysfunction. However, age, coronary artery disease and aortic rupture showed an association with TND, as shown in Table 6A. ⇓
None of the intraoperative factors were associated with a higher risk of TND in this group. Significant predictors of transient neurological dysfunction in multivariate analysis of the group as a whole were increasing age (OR 3.4 and 7.0 in the second and third tertile as compared with the lowest tertile) and any coronary heart disease (OR 3.4) (Table 7).
Cumulative survival rates of all patients (median follow-up 34 months) was 55% at one, 49% at five and 44% at 8 years. (Figure 1). It can be derived from the figure that acute mortality until hospital discharge was excessively high, whereas long term survival in discharged patients was excellent.
Acute type A dissection is a catastrophic event that still represents a formidable surgical challenge. Treated nonoperatively, 90% of all patients with acute dissection will die within 2 weeks.9–11
Therefore, current management philosophy favors immediate surgical intervention, for which results have steadily been improving because of enhanced preoperative diagnosis, development of better prosthetic materials, amelioration of cardiac as well as cerebral protection, and increased surgical experience.4 In this study, an unselected consecutive series of 167 patients with acute type A dissection was analyzed to determine risk factors responsible for adverse outcome and temporary neurological dysfunction. We elected to combine permanent neurological injury and death as adverse outcome to increase our sensitivity in identifying preoperative and procedural risk factors, and because the risk of permanent neurological injury is often as worrisome to prospective patients as the chance of dying, and is often associated with early mortality.12
Furthermore, we also wanted to examine the syndrome “transient neurological dysfunction,” because previous studies have consistently shown TND to correlate with duration of cerebral ischemia, in contrast with permanent neurological injury, which is predominantly focal, and for which prolonged HCA has not invariably emerged as a risk factor.8 In addition to being a reflection of suboptimal cerebral protection, recent evidence has also suggested that TND seems to be a marker of long-lasting but subtle cognitive impairment.7
The overall adverse outcome rate in our study appears to be relatively high on initial inspection. However, Fann and colleagues reported a 26% mortality rate in 174 patients with acute type A dissections.13 Similar results were also found in a series by Bavaria, where the 60-day mortality rate in 41 patients with acute type A dissection was 29%.14 Moreover, changing patient substrate to a higher-risk cohort may provide another explanation for these high adverse outcome rate. Fifty-seven percent of the patients in our study had aortic rupture at the time of surgical intervention and 22% of our patients were hemodynamically unstable preoperatively, which is higher than in most of the other reported cases.13,15
Only hemodynamic instability was found to be a statistically significant independent risk factors for adverse outcome in our patient population. This is not surprising and results reported by others would lead to the expectation that patients with frank rupture and hemodynamic compromise would have a worse outcome than patients who are stable preoperatively.
Although longer HCA times have been associated with neurological dysfunctions, this variable was not a risk factor for adverse outcome in this series, indicating that inadequate cerebral protection was not a major contributor to adverse outcome. This suggests that meticulous attention to the implementation of HCA—thorough cooling and packing the head in ice—results in sufficient protection to avert serious neurological morbidity for the duration of HCA required to resect the intimal tear and perform an open distal anastomosis.
A history of COPD was a predictor of adverse outcome in this study, as was previously shown to be the case for nondissecting thoracic and thoracoabdominal aneurysms.16 COPD was first recognized as being associated with a high risk of rupture of aneurysms in the abdominal aorta by Cronenwett and associates, and it has been speculated that there must be a common, possibly smoking-related defect in connective tissue metabolism that predisposes toward both lung and aortic pathology in susceptible persons.17,18
We were surprised that the use of retrograde cerebral perfusion did not reduce the risk of adverse outcome in this study. Although several authors and our group have reported excellent results using RCP in the past, we were unable to prove any beneficial effect of this technique in this series.19,20
The fact that we saw no impact of retrograde cerebroperfusion on the incidence of adverse outcome in this study may be a result of combining both death and permanent neurological dysfunction as adverse outcome, and of having examined a larger number of patients. We still believe, however, that the major benefit of RCP can be explained by the sustained intracranial cooling during HCA and may therefore, enhance the topical cooling effect of ice-bags around the head.
The occurrence of temporary neurological dysfunction in 16% of patients warrants some concern, given that recent evidence suggests that this syndrome may be associated with permanent although subtle loss of cognitive function in a majority of the patients in whom it occurs. It is clear from a number of studies that the incidence of transient neurological dysfunction climbs steadily with increasing durations of HCA, and that intervals of HCA exceeding 25 to 30 minutes are best avoided.20 Although HCA turned out not to be a statistical significant risk factor in univariate analysis, patients with circulatory arrest time of greater than 40 minutes had a higher incidence of TND than those with HCA times of less than 40 minutes.
The emergence of coronary artery disease as an independent risk factor for the occurrence of TND is interesting. We speculate that the presence of coronary artery disease may be an indicater of cerebrovascular atherosclerosis in these patients, which puts them at higher risk of cerebral dysfunction postoperatively.
The finding that advanced age is a risk factor for transient neurological dysfunction is not unexpected, and is in accord with our own earlier findings and the observations of others.7,8,22
That the location of the intimal tear and the performance of concomitant procedures failed to have any impact on mortality is also reassuring, suggesting that the current approach at our institution, which involves resecting the site of the intimal tear and performing adjunctive procedures when clinically indicated, is a reasonable way to deal with acute dissections in a setting in which aneurysm surgery is a routine procedure. A Bentall procedure was almost invariably carried out, but various different approaches to the aortic valve—leaving it untouched, replacing it, or resuspending the valve leaflets—also had no impact on mortality. It is possible, however, that some aspects of these results may not easily be extrapolated to institutions with less experience with dissections and aneurysms. It must be emphasized that the principal object of emergency surgery for acute dissection must be the immediate survival of the patient, and more limited operations may be more appropriate under particular circumstances.
In conclusion, surgical treatment of acute type A dissections with resection of the intimal tear and use of hypothermic circulatory arrest for distal anastomosis is still associated with a high incidence of adverse outcome. The aim in the treatment of this very sick cohort of patient is earlier recognition of the underlying pathology (diagnosis of hypertension, annual CT-scans) and elective surgery.
Limitations of the Study
The study accumulated data from a single institution over a rather long period of 15 years, and surgical technique, patient monitoring, and acute therapeutic techniques certainly evolved during the recent years. However, we believe that the main risk factors remained unchanged during this time period and that our data therefore allow relevant conclusions.
Miller DC, Mitchell RS, Oyer PE, Stinson EB, Jamieson SW, Shumway NE. Independent determinants of operative mortality for patients with aortic dissections. Circulation. 1984; 70 (suppl I): 153–164.
Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi HJ. Dissection of the aorta and dissecting aortic aneurysms. Circulation. 1990; 82 (suppl IV): IV24–IV38.
Fann JI, Smith JA, Miller DC, Mitchell RS, Moore KA, Grunkemeier G, Stinson EB, Oyer PE, Reitz BA, Shumway NE. Surgical management of aortic dissection during a 30-year period. Circulation. 1995; 92 (suppl II): II113–II121.
Bavaria JE, Woo JY, Hall RA, Wahl PM, Acker MA, Gardner TJ. Circulatory management with retrograde cerebral perfusion for acute type A aortic dissection. Circulation. 1996; 94 (suppl II): II173–II176.
Okita Y, Takamoto S, Ando M, et al. Predictive factors for postoperative cerebral complications in patients with thoracic aortic aneurysms. Eur J Cardiothorac Surg. 1996; 10: 826–832.