Midterm cerebral outcomes of Stanford type A aortic dissection in patients who underwent novel triple‐branched stent graft implantation combined with intraoperative monitoring of regional cerebral oxygen saturation

Abstract Objective The aim of this study was to evaluate the cerebral outcomes of patients underwent novel triple‐branched stent graft implantation combined with the intraoperative monitoring of regional cerebral oxygen saturation. Methods One hundred thirty‐seven consecutive patients who underwent the surgery of triple‐branched stent graft implantation in our department were enrolled in this retrospective case‐control study. The patients in group A received brain protection based on the intraoperative monitoring of regional cerebral oxygen saturation and the patients in group B received conventional brain protection. The general clinical data, the types of corrective surgeries, the intraoperative situations, the postoperative complications, and the midterm outcomes of the patients were analyzed. Results The incidence of postoperative cerebral dysfunction in the patients of group A was significantly lower than that in the patients in group B (3.2% vs 14.9%, P = .020). We found significant differences in the incubation times (30.3 ± 22.1 vs 42.3 ± 27.9 hours, P = .014), the lengths of intensive care unit stay (58.0 ± 54.3 vs 79.7 ± 55.5 hours, P = .004), and the hospital stays (19.3 ± 6.7 vs 24.9 ± 17.3 days, P = .045). A descending trend in the mortality rates was observed between the patients in the two groups based on the 20 months of observation; however, this trend was not statistically significant (1.6% vs 6.8%, P = .218). Conclusions The novel triple‐branched stent graft implantation procedure combined with intraoperative monitoring of the regional cerebral oxygen saturation was an effective treatment for Stanford type A aortic dissection, with a relatively low incidence of postoperative cerebral dysfunction.

ranging from 8.6% to 10.7%) [1][2][3] It is currently known that the main mechanism of postoperative cerebral dysfunction is the disbalance of oxygen metabolism in the brains of patients. Compared with conventional monitoring methods, regional cerebral oxygen saturation (rcSO 2 ) can provide much earlier warning indications of cerebral hypoxia. The aim of this study was to evaluate the cerebral outcomes of patients who underwent novel triple-branched stent graft implantation with intraoperative rcSO 2 monitoring. 2.1 | Exclusion criteria 1. Patients who were younger than 16-years of age.

2.
Patients who underwent other types of procedures (eg, Sun's procedure).
3. Patients with an abnormal preoperative consciousness.

4.
Patients and/or their relatives who did not agree to participate in this clinical study.

5.
Patients who were lost to the 20-month follow-up.

| Diagnosis criteria of the postoperative cerebral dysfunction
Postoperative cerebral dysfunction included new-onset stroke, syncope, delirium, postoperative cognitive dysfunction (POCD), delayed emergence from anesthesia (DEA), and coma, which were confirmed by two experienced neurologists. Deeply sedated patients, confirmed by the monitoring sedation status system of the Richmond Agitation Sedation Scale (RASS), 4 did not receive any evaluation of cerebral function until they recovered from anesthesia.
The diagnosis of a stroke was based on the National Institutes of Health Stroke Scale. 5 Syncope was defined as a transient loss of consciousness and was characterized by a rapid onset, short duration, and spontaneous complete recovery. 6 The confusion assessment method for the intensive care unit 7 was applied for the evaluation of postoperative delirium (POD) and POCD. The Glasgow Coma Scale 8 was used to objectively define coma in the two groups of patients after their surgeries. The patients whose response to stimulation occurred more than 60 to 90 minutes after the surgeries were recognized as having a DEA, 9 and this diagnosis should exclude the possibility of the other types of cerebral dysfunction mentioned above.

| Protocols of anesthesia
Combined intravenous inhalation anesthesia was applied in the patients.
The nasopharyngeal temperature and the rectal temperature were monitored. Transesophageal echocardiography (TEE) was applied to monitor the intraoperative hemodynamics. Autologous blood transfusion was used to reduce the allogeneic blood transfusion. The balances of cerebral oxygen metabolism of the patients were measured by rcSO 2 with the Regional Oximetry System (INVOS 5100C, Medtronic). The bispectral index (BIS), which was measured by the BIS Monitoring System (VISTA, Covidien), was used to measure the depth of anesthesia.
During the surgery, the values of scSO 2 were maintained at or above 70% of the baseline threshold. Cerebral desaturation was defined as a decrease in the saturation value below the absolute value of 50% or 70% of the baseline for 15 seconds. The mean and minimum values of the rcSO 2 , as well as the area under the curve (AUC) of the rcSO 2 values below the line of the previously mentioned cerebral desaturation values, were collected for further analysis.

| Surgical procedure
During surgery, the arterial pressures of the upper and lower limbs were monitored. A sternal incision was performed. To establish CPB, the arterial cannula was placed in the right axillary artery and the right femoral artery, and the drainage tube was placed in the right atrium. The CPB flow rate was 2.4~2.6 L·kg −1 ·min −1 . Intermittent F I G U R E 1 Flow Chart. The patients were divided into two groups: patients in group A received brain protection based on the intraoperative rcSO 2 monitoring (n = 63), and patients in group B received conventional brain protection (n = 74). Thirty-five patients were excluded from this study according to the exclusion criteria described in detail below cold-blood cardioplegia was perfused through the left and right coronary arteries for myocardial protection. The following procedures, including the triple-branched stent graft implantation, can be found in our previous literature. 2

| Protocol to deal with intraoperative cerebral desaturation
In group A, the positions of the patients were checked first to exclude the compression of the cervical great vessels when intraoperative cerebral desaturation occurred. Then, the parameters of the mechanical ventilator (before or after CPB) or the oxygenator (during CPB) were adjusted to maintain the arterial pressure of CO 2 (PaCO 2 ) above 40 mm Hg. Metaraminol or noradrenaline was used to elevate the mean arterial pressure to above 60 mm Hg. A cardiotonic (eg, epinephrine) was administered if there was a poor cardiac index (below 2.0 L·m −2 ·min −1 ), and adequate blood volume was confirmed by TEE. The BIS value was maintained at or below 50 during the CPB to ensure that patients were in a state of deep anesthesia. Other methods to prevent cerebral hypoxia included increasing the pump flow, increasing the FiO 2 and performing allogeneic blood transfusion. The patients in group B received conventional brain protection strategy without the guidance of intraoperative rcSO 2 monitoring. 1-3

| Follow-up
Telephone contact with the patients was maintained after discharge.
Every month in the first year, the patients received echocardiographies, chest radiographies, and bilateral carotid artery Doppler examinations. At one and 3 months after surgery, the patients received aortic computed tomography angiography examinations which were then performed annually.

| Statistical analysis
SPSS Statistics (version 19.0, IBM) was used for the statistical analyses. Descriptive statistical analyses, as well as Wilcoxon ranksum tests, were used to analyze the measurement data. The χ 2 test or the Fisher exact test was used to analyze the numerical data. The Kaplan-Meier method was used to plot the survival curves. Statistical significance was defined as P < .05.

| General clinical data
Thirty-five patients were excluded from this study, including five cases that were younger than 16 years of age, 18 cases that underwent other types of procedures, 10 cases that were coma before surgeries, and two cases that were lost to the 20-month follow-up.
The primary analyses revealed that there were no significant differences between the patients in the two groups in terms of age, sex, body mass index, personal history, underlying diseases, New York Heart Association class, etiologies, ultrasound cardiogram results, preoperative complications due to aortic dissections, the scales of aortic dissections, the American Society of Anesthesiologists class and EuroSCORE II values ( Table 1).
The χ 2 test revealed that there were no significant differences in the types of surgical procedures between the patients in the two groups. The Wilcoxon rank-sum tests also indicated that the duration of surgery, CPB, aortic cross-clamping, moderate hypothermic circulatory arrest (MHCA) + selective cerebral perfusion (SCP), the mean value of the intraoperative BIS index, the volumes of blood loss, and perioperative allogeneic transfusion had no significant differences in the patients in these two groups ( Table 2).

| Intraoperative rcSO 2 value
The patients in group A received intraoperative rcSO 2 monitoring, and the baseline values of rcSO 2 were in the normal range; the average values during the surgeries were 64.4% ± 6.0% (L) and 61.3% ± 6.9% (R), and the minimum value was 45.8% ± 12.5%. The frequency of the rcSO 2 declined to the level of 70% of baseline (which lasted for at least 15 seconds) was 4.4 ± 2.6 times in a single operation, and the number reached a value of 1.3 ± 1.6 when the level decreased to 50% of baseline. Further analysis of the rcSO 2 value revealed that the AUCs of the rcSO 2 below the level of 70% of baseline were 66.2% ± 39.5% min (L) and 50.5% ± 31.3% min (R), and the AUC changed to 27.1% ± 32.5% min (L) and 25.8% ± 24.8% min (R) when the level decreased to 50% of baseline (Table 2). At the beginning of the induction, an obvious peak value of rcSO 2 could be observed due to the inhalation of 100% oxygen before intubations. Afterward, we observed a slow decline in the rcSO 2 value, which was associated with the establishment of the CPB. The

| Postoperative situation
Thirteen (13 of 137, 9.5%) patients with postoperative cerebral complications were observed. The Wilcoxon rank-sum tests showed that the anesthesia recovery periods of the patients in group A were notably shorter than those of the patients in group B, and the Fisher exact test showed that there were significant differences in postoperative cerebral dysfunction between the patients in the two groups. One case of POD and one case of POCD were discovered in the patients in group A. There were two cases of new-onset stroke, one case of syncope, two cases of delirium, one case of POCD, two cases of DEA, and two cases of coma in the patients in group B. Two patients with postoperative paraplegia were also observed in group B, but no significant differences were found between the two groups. We also discovered significant differences in intubation time, length of stay in the intensive care unit (ICU), and length of hospital stay ( Table 3).
The non-neurological complications observed after the surgeries included reoperations for bleeding, heart dysfunction, myocardial infarction, lethal arrhythmia, renal insufficiency, pulmonary infection, gastrointestinal complications, wound infection, sepsis, acute respiratory distress syndrome, and multiple organ dysfunction syndrome. The rates of the use of intra-aortic balloon pumping and/or extracorporeal membrane oxygenation were confirmed to be proximate between the two groups (Table 3).
Six cases of death were observed in this study, including four cases that occurred in the hospital and two cases that occurred after discharge. The Fisher exact test showed that there was no significant difference in the mortalities of the patients in the two groups, but we observed a decreasing trend in mortality after the surgeries that involved intraoperative rscO 2 monitoring. Wilcoxon rank-sum tests also showed that patients in group A spent markedly less money than the patients in group B (Table 3).

| Follow-up
One patient was lost to the 20-month follow-up and was excluded from this study. Two incidences of death after discharge (both of them occurring in group B) were observed and were attributed to low cardiac output syndrome and recrudescence of the aortic dissection.