Risk factors for cerebral complications after type A aortic dissection surgery: single center’s experience

Introduction

Cerebral complications (CC) are severe postoperative complications of type A aortic dissection (TAAD) surgery. The rate of CC has been reported be as high as 10–30% and will increase the rate of mortality 2- to 3-fold (1,2). Previous retrospective studies found that the methods of aortic arch surgery, arterial cannulation, hypothermic strategy and cerebral perfusion were risk factors of CC (3).As results from different studies were controversial, there are no standards of cerebral protection during TAAD surgery. And no prospective randomized trial is available for TAAD surgery, thus we retrospective reviewed the data from our center with a large cohort to analyze the risk factors for CC after TAAD surgical repair.

We present the following article in accordance with the STROBE reporting checklist (available at https://dx.doi.org/10.21037/apm-20-2365).

Methods

Patients

From January 2010 to December 2017, 746 patients diagnosed with Stanford TAAD underwent surgery in our center. Among them, 711 patients had not developed CC (non-CC group), and 35 patients were diagnosed with CC (CC group) after surgery. Six patients had intra cranial hemorrhage, and 29 patients had ischemic infarct stroke. All patients in the CC group received head CT scans, and positive intracranial lesions were identified. CC referred to those of a focal (stroke) or global (parkinsonism, coma, gait disturbance) nature that persisted at discharge from the hospital (4).

The clinical preoperative, operative, and postoperative characteristics were collected through the electronic charts of all patients. We retrieved the data retrospectively by a review of hospital records, and individual consent for this retrospective analysis was waived. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of Nanjing Drum Tower Hospital (No. 2020-185-01).

Surgical approach

The surgical approaches were reported in our previous articles on TAAD. We chose different methods for aortic arch repair according to the patients’ anatomic indications (5-7). Partial aortic arch replacement was defined as conservative arch repair (CAR), and total arch replacement and arch stent procedures were defined as total arch repair (TAR). In a subsequent propensity-score matching analysis, the TAR group was divided into two subgroups: the Total-arch group and the Arch-stent group. Root repair was performed with the reinforcement reconstruction method as previously reported (8,9). The Bentall procedure was performed as described in the literature.

Cannulation and cerebral perfusion method

The right axillary artery and femoral artery were the first choices for arterial cannulation. Based on the expected duration of the circulatory arrest and the intended surgical procedure, we decided to use antegrade cerebral perfusion (ACP), retrograde cerebral perfusion (RCP) or no cerebral perfusion. Intraoperative cerebral oxygen testing was used to assess the effectiveness of intraoperative cerebral perfusion. When the value was below 20% of the baseline, we considered the cerebral perfusion to have had an effect and obtained additional measurements. For an expected arrest time of more than 30 minutes, the target value of cerebral temperature (Nasopharyngeal temperature) was 18–20 °C. For an arrest time of less than 30 minutes, the target value was 20–22 °C. Only a very small number of patients were assigned a cerebral temperature of 25 °C. In the ACP subgroup, before December 2015, we used an ACP perfusion rate of 6–10 mL/kg/min. After January 2016, we have further reduced the flow rate to 3–5 mL/kg/min.

Statistical analysis

Continuous variables are presented as the mean ± standard deviation (after verifying the normality of the distribution of the data). Categorical variables are presented as absolute numbers and proportions. Data analysis was performed using SPSS 23 Statistics software (IBM, Herrenberg, Germany). Differences in categorical variables were analyzed using the χ² test. Differences in continuous variables were tested using the t-test, or the Mann-Whitney U test, respectively. Multivariable analysis was performed using a binary logistic regression model to discriminate independent risk factors for 30-day mortality and CC. Kaplan-Meier survival analysis was used to compare the long-term follow-up survival rate between the non-CC and CC groups in terms of the odds ratio (OR) and the 95% confidence interval (CI). A value of P<0.05 was considered statistically significant. In the propensity-score matching step, sex, age, and other preoperative characteristics were entered into a logistic regression model to estimate the propensity score. The best balance was reflected by a standardized difference below 10%.

Results

Comparable analysis between the non-CC and CC group

The average age was 52.1±13.0 years, and 75.9% of the patients were male. The mean body mass index (BMI) was 25.6±3.9 (kg/m²). A total of 575 patients (77.1%) had hypertension. Cerebral malperfusion was more common in the CC group (non-CC vs. CC, 9.6 vs. 40.0%, P=0.000). The ratio of permanent preoperative cerebral ischemic events was significantly higher in the CC group (P=0.001). According to the preoperative critical status, more patients in the CC group received emergent or salvage operations, although the difference with the non-CC group was not significant (P=0.060). The total average of operation time was 8.4±2.0 hours, with cardiopulmonary bypass (CPB) and aortic clamp times of 247.3±83.6 and 169.4±64.5 minutes, respectively. The average time of hypothermic cerebral arrest (HCA) was different between the two groups (non-CC vs. CC, 29.3±12.0 vs. 31.1±8.7 minutes, P=0.036). CAR induced significantly lower rates of CC. Access through the axillary artery had the lowest rate of CC. A total of 3.4% of patients with a low flow rate and 7.0% with a normal flow rate experienced CC (P=0.035). The 30-day mortality was 13.3% (99/746); patients in the CC group had significantly higher mortality than those in the non-CC group (non-CC vs. CC, 12.2% vs. 34.3%, P=0.001). The proportion of patients with prolonged mechanical ventilation was higher in the CC group (non-CC vs. CC, 18.3% vs. 37.1%, P=0.006). A total of 1.5% patients of all patients developed paraplegia, which was more common in the CC group (non-CC vs. CC, 1.0% vs. 11.4%, P=0.001). Other morbidities of common complications were nearly similar (Table 1).

Table 1 Characteristics in patient with post operation cerebral complications (CC) and without that (non-CC) in a retrospective analysis
Full table

In multivariable analysis, risk factors for mortality included age, tamponade, end-stage kidney disease (ESKD), operation time, salvage surgery, CC, extracorporeal membrane oxygenation (ECMO) support, continuous renal replacement therapy (CRRT) and re-intubation (Figure 1A). The independent risk factors for CC were preoperative cerebral ischemia, limb ischemia, ESKD, and salvage surgery (Figure 1B). Postoperative risk factors were paraplegia and mechanical ventilation. A low flow rate in ACP was a protective factor both for both mortality and CC, and CAR acted as a protective factor for CC. After adjustment, CAR (P=0.044; odds ratio, 4.587; 95% CI: 1.045–20.130) and a low flow rate in ACP (P=0.046; odds ratio, 2.139; 95% CI: 1.014–4.515) remained protective against CC (Table 2).

Figure 1 The results of the risk factors for postoperative CC and mortality from multivariate logistic regression analysis. (A) Risk factors for postoperative CC from multivariate logistic regression analysis; (B) risk factors for postoperative mortality from multivariate logistic regression analysis. CC, cerebral complications.

Table 2 Results of multivariable logistic regression of postoperative cerebral complications after adjustment
Full table

In the Kaplan-Meier survival analysis, we found that there were no differences between the non-CC and CC groups (P=0.68, Figure 2).

Figure 2 Follow-up results of comparing CC and non-CC patients. CC, cerebral complications.

CAR: propensity-score matching analysis

Three groups with 135 patients in each group were compared. Preoperative risk factors were consistent without differences. The times of CPB, X clamp and HCA were all significantly different. The CPB time was longer in total-arch group (non-arch vs. total-arch vs. arch-stent: 218.5±61.5 vs. 265.3±90.0 vs. 223.7±124.6 minutes, P=0.000); similar observations were made for X clamp and HCA time. The morbidity rate for CC was higher in the Arch-stent group (non-arch vs. total-arch vs. arch-stent, 0.7% vs. 3.0% vs. 8.9%, P=0.000), and the mortality rate was higher in the total-arch group (non-arch vs. total-arch vs. arch-stent, 9.6% vs. 17.0% vs. 11.9%, P=0.175) (Table 3).

Table 3 Among different arch methods group in a perspective study
Full table

Low flow rate in ACP: propensity-score matching analysis

Two separate groups of 148 patients each were compared. No differences were found in baseline demographic data, surgical methods, or intraoperative details. However, both the rate of CC and mortality were higher in the normal flow rate group (normal vs. low flow rate in ACP, CC: 10.8% vs. 5.4%, P=0.067; mortality: 19.6% vs. 8.8%, P=0.012) (Table 4).

Table 4 Low and high flow rate in ACP in a perspective study
Full table

Discussion

Prevalence and risk factors

TAAD is a lethal disease with high mortality and morbidity despite improvements in surgical techniques and organ protection methods. CC are the main complications after surgical repair for aortic dissection. In an STS database review, the operative mortality was 17%, and the incidence of postoperative stroke was 13% (3). The German registry for acute aortic dissection type A reported that the incidence of permanent neurological dysfunction (PND) was 13.4%, the 30-day mortality was 15.9%, and PND patient mortality was 21.5% (2). The Japanese adult cardiovascular surgery database revealed a mortality of 6.1% and a stroke rate of 7.0% among all patients with total arch replacement, but the subgroup of aortic dissection comprised only 22.9% of the total (10). Wang and colleagues investigated the largest group from China, consisting of 1,708 patients with 57.8% of acute aortic dissection, and the overall PND rate was 4.8%, with a mortality of 6.1% (11). Our single-center results were are nearly consistent with these results obtained from a patient database.

Preoperative cerebral ischemia has a strong relationship with postoperative CC and mortality, but the indications for emergent surgery for these patients are not clear. Of the 1,873 patients with type A dissection enrolled in IRAD, 87 (4.6%) presented with cerebrovascular accidents, and 54 (2.9%) presented with coma (12). In our experience, 11.0% (82/746) of patients had preoperative cerebral ischemia, and only 1.3% had preoperative PND. Among them, 14 patients developed CC after surgery, 6 of them with PND before surgery. IRAD found that surgery led to a hospital survival benefit of 49.6% in patients with preoperative neurologic symptoms and 55.6% in those with coma (12). Therefore, we must continue to attempt surgical repair first for these patients with cerebral ischemia.

Brain protections methods: conservative arch repair

In addition to preoperative cerebral ischemia including CC after surgical repair for TAAD, intraoperative brain protection methods are the key factors impacting cerebral outcomes. Ghoreishi listed cannulation strategy, degree of hypothermia, cerebral perfusion method and techniques for arch repair as the main factors that could impact postoperative cerebral complication (3). Among them, hemiarch surgery was shown to play a protective role for the brain. We identified CAR as having a lower rate of CC and mortality than TAR in both the retrospective analysis and propensity-score matching analysis. However, our results are inconsistent with those from retrospective reviews. Rice et al. studied 489 patients who underwent TAAD surgery, and the rate of stroke was not significantly different between the total arch group (8.2%) and the hemiarch group (10.5%) (13). Rylski et al. also found similar neurological outcomes in a cohort, but TAR was a strong predictor for mortality (14). However, Roselli et al. found that the rate of reintervention for patients with hemiarch repair was 38% within 10 years, which suggested more aggressive techniques for arch repair in TAAD (15). In the present study, TAR included arch surgery with arch stents, as described in previous studies (5,6). Arch stents are used to simplify the arch surgery and achieve a reshaping effect with the frozen elephant trunk technique. However, the rate of CC was higher than that of the total arch and CAR groups, while the mortality was lower than that of the total arch group and similar to that of the CAR group. One possible reason for these differences was that the underestimation of the incidence of CC in the case of high mortality in the total arch group. Another was that arch manipulation could not be avoided during the arch stent procedure. During the HCA period, we had to clamp the innominate artery and left common carotid artery, then insert the arch stent system and release it in anatomical proximity to the proximal artificial vessel. Arterial clamping injury and the potential risk for blood flow from a new stent in the arch position are all possible origins of thrombi and low perfusion, respectively. We considered the possibility of aggressive arch repair to reduce the rate of reintervention, but the method of arch stent repair still has limitations and disadvantages for brain protection based on our results. Investigating the indications and optimizing the surgical manipulations are necessary in future studies.

Brain protection methods: cerebral perfusion and flow rate

In our series, we used different perfusion methods, including direct HCA without perfusion, ACP and RCP, but all had similar rates of CC. HCA is a basic method for aortic arch surgery where body temperature is lowered to preserve organ function and reduce metabolic demand (16). The safety duration of HCA ranges between 25–60 min. The researchers found that an HCA duration longer than 40 minutes will increase the risk of postoperative CC and mortality (17). Despite the safe duration, direct HCA have revealed similar risk for CC. Ghoreishi et al. found that 29% of patients in their cohort had not received an adjunct technique for cerebral perfusion, but it was not found to be a risk factor for postoperative stroke (3). However, in our series, the average time for HCA in the TAR group was longer than 30 minutes, which meant for most patients with HCA, no cerebral perfusion was exposed to damage caused by a prolonged HCA time. This is why adjunct methods are necessary. ACP is widely used and can be physiologically adapted when the duration of ACP is longer (18-21). Keeling et al. retrospectively reviewed 342 patients using moderate hypothermic circulatory arrest and selective ACP. The median circulatory arrest time was 38.9 minutes, the mortality was 11.7%, and the rate of PND was 7.3% (19).In a propensity-score matching analysis consisting of 925 elective aortic arch surgery patients with ACP or HCA alone, the mortality and PND rates were all significantly lower in the ACP group (3.8% and 2.9%, respectively) (21).

However, no results on the superiority of ACP in TAAD arch surgery have been confirmed. Angleitner et al. reported on both unilateral and bilateral ACP for TAAD arch surgery. During the average HCA time of 34 minutes, the rate of PND was 19.0%, and the mortality rate was 14.1% (22). This perplexed us in the early stage after the burden of ischemia resolved with the aid of adjunct ACP. The concepts regarding direct HCA and the clinical findings of facial edema after ACP + HCA surgery inspired us to also consider the burden of luxury-over perfusion from ACP. Autoregulation of cerebral circulation is the key physiological function for maintaining the related normal flow for the brain (23,24). However, cerebral autoregulation can become dysfunctional when the body cools to temperatures lower than 22 °C. This means that the resistance of cerebral vessels will not increase to adapt to ischemia, and the blood flow of the cerebral circulation will increase, which may be a potential risk factor for increased intracerebral pressures, cerebral edema, and microvascular damage. The weight of normal human adult brain is 1.5% to 3.0% of that of the whole body, and the normal physiological cerebral blood flow is 55 mL/min/100 g of cerebral matter. This means that a blood flow of nearly 8–16 mL/kg/min is necessary at baseline of physiological demand. However, when the temperature decreases, the physiological demand also decrease, reaching is nearly 30% of the baseline at 22 °C (25). Therefore, we chose 3–5 mL/kg/min as the perfusion flow rate.

An animal model was used to show that a higher perfusion rate in ACP can not only improve cerebral perfusion to improve metabolism, but also cause intracranial edema (26). No clinical trials can be performed to compare the different flow rates applied for ACP for ethical reasons, but the clinical experiences from our center present new proof of the benefit of a low flow rate for ACP. We used NIRS to detect the cerebral metabolism and adjusted the flow rate based on the baseline value and variated value.

Limitations

This article is a retrospective analysis from a single center. Even with a large cohort of cases, the bias of such a study design cannot be ignored. We attempted to adjust for the preoperative factors in two separated propensity-score matching analyses, but the missing data during this processaffeced the real results. Otherwise, TAAD is primarily emergent or urgent surgery, which we cannot compare factors in an RCT. The data from our single center reflect the results from a real-world experience.

Conclusions

In conclusion, our single-center results for TAAD repair, including a mortality of 13.3% and rate of CC of 4.7% were interesting. Preoperative status remained the key factor inducing mortality and adverse cerebral outcomes. Conservative arch repair had lower mortality and morbidity than total arch repair for TAAD, but considering the necessity of TAR, the technique also achieved acceptable results. Low flow rate in ACP may be a safer and potentially better technique for cerebral protection, but it must be compared with traditional methods in the further prospective studies.

Acknowledgments

Funding: This work has been supported by the National Key R&D program of China (2016YFC1000808), National Natural Science Foundation of China (No. 81970401, No. 81670437) and Jiangsu Provincial Key Medical Discipline (ZDXKA2016019).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://dx.doi.org/10.21037/apm-20-2365

Data Sharing Statement: Available at https://dx.doi.org/10.21037/apm-20-2365

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/apm-20-2365). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. We retrieved the data retrospectively by a review of hospital records, and individual consent for this retrospective analysis was waived. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of Nanjing Drum Tower Hospital (No. 2020-185-01).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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