Introduction
Aortic dissection (AD) refers to the pathological change where blood enters the media through the intimal tear and extends along the long axis of the aorta, peeling off the aortic wall and resulting in the separation of true and false lumens. The disease’s progress leads to the symptoms and signs of the corresponding organ blood supply disorder [
1]. Stanford Type A aortic dissection (TAAD) has a high in-hospital mortality rate of 12.7–27.7% [
2]. The mortality rate increases by 1–2% per hour in early untreated patients, with a mortality rate as high as 60–70% within one week [
3]. Emergency surgery is currently the most effective treatment method, and the postoperative mortality rate has considerably decreased in recent years. However, patients are prone to neurological dysfunction after surgery because of the complexity of the operation, long operation time, and impact on brain tissue perfusion [
4,
5].
Postoperative delirium (POD) is one of the common neurological complications in TAAD patients following surgery. It is an acute and reversible state of confusion characterized by fluctuating consciousness disorder, inattention and thinking disorder [
6]. The incidence of POD in AD is approximately 32.5–52.0% [
2]. Delirium leads to prolonged mechanical ventilation time and ICU stay, increased postoperative readmission possibility. It also increases the psychological pain of caregivers, economic burden, and the work pressure on medical teams [
7,
8]. Furthermore, the occurrence of POD is closely related to increased postoperative mortality, higher medical expenses, long-term cognitive impairment, and decline in quality of life, leading to poor prognosis of patients [
9,
10]. Early screening and management of delirium can reduce hospital mortality and the incidence of postoperative complications; it can also reduce the care burden of caregivers and the treatment and nursing pressure on medical and nursing teams [
11‐
13]. As a result, it is vital to identify its risk factors, as many scholars have analyzed the risk factors of POD in TAAD patients. Common risk factors include cerebrovascular disease history, intubation time, surgery duration, renal insufficiency and hypoxia, etc.[
14,
15]. However, the research results are controversial. For instance, Lv et al. [
14] confirmed that age was a high-risk factor for POD, while Liu et al. [
15] reported that age was not an independent risk factor for POD in TAAD patients. This controversial conclusion has brought some confusion in determining the high-risk factors for POD. Therefore, the purpose of this study is to identify risk factors by integrating and analyzing the existing literature on POD in TAAD patients This will help accurately identify high-risk groups and provide an evidence-based foundation for clinical medical staff to develop targeted perioperative treatment and management measures.
Discussion
Delirium is a serious and complicated neurological complication in patients with TAAD. Cai et al. [
22] found that patients with POD had longer ICU stays by 4.3 days and hospital stays by 5.08 days, respectively, when compared to those without delirium. Therefore, it is of great significance to identify and intervene in the risk factors of POD in patients with TAAD. This study systematically evaluated the risk factors for delirium in TAAD patients through meta-analysis, and ultimately included 9 studies. The literature quality was high, and the meta-analysis results were relatively reliable. The present study found that the incidence of POD fluctuated from 14.03 to 50.4%, and POD was associated with the patient’s ICU stay and hospitalization time. In this meta-analysis, we found 12 influencing factors.
The results of this study showed that age was one of the risk factors for POD in TAAD patients. Katarzyna et al. [
25] reported that the incidence of delirium after cardiac surgery was 21.4% in patients aged over 65 years old, while 33.5% in patients over 80 years old. Mu et al. [
26] found that the incidence of delirium increased by 8% with each year of age. The possible reasons are the continuous deterioration of brain metabolism and central nervous function with the increase in age, the decline of the self-regulation function of cerebral blood flow, and the easy occurrence of insufficient cerebral perfusion during surgery, resulting in damage to the neurotransmitter function [
27]. In addition, elderly patients are mostly accompanied by chronic diseases. Their basic cognitive level is also affected to varying degrees, thereby increasing the risk of POD in the elderly.
Preoperative low hemoglobin levels were regarded as a risk factor for POD in TAAD patients. Preoperative low hemoglobin levels may lead to neurotransmitter imbalances, disruption of the brain barrier, and neuroinflammation due to decreased oxygen carrying capacity of the blood and insufficient oxidative metabolism of the brain. This can result in various levels of mental symptoms and even delirium [
28]. Visser et al. suggested that preoperative low hemoglobin levels may be associated with an increased risk of delirium [
29]. Therefore, the anemia status of TAAD patients with preoperative low hemoglobin levels should be corrected in time. Monitoring and prevention of POD should also be carried out.
BMI, an important index reflecting human nutrition and health status, is considered one of the risk factors for POD in TAAD patients. An abnormal BMI (overweight or obesity) may be linked to hyperlipidemia, which can cause problems with brain microcirculation, as well as ischemia and hypoxia in the brain tissue, which can result in cognitive dysfunction [
30]. In addition, obstructive sleep apnea syndrome is also more severe in obese people, which causes transient hypoxia, inflammation, and oxidative stress in the body. This worsens the condition of nervous system malfunction [
31].
The findings of the present study indicated that history of cardiac surgery is also a risk factor for POD in TAAD patients. Surgery is a serious trauma to the body, and repeated surgeries causes could induce a state of stress. This condition can lead to increased levels of adrenaline and norepinephrine, accelerated cerebral blood flow, increased oxygen consumption, norepinephrine–acetylcholine imbalance, and a series of neurological complications. Furthermore, stress can increase the activity of cholinesterase in the brain, enhance the metabolism of acetylcholine, and reduce the acetylcholine content, thereby inducing delirium [
32].
This study found that renal insufficiency before and after surgery was a risk factor for POD in TAAD patients. The patient’s preoperative renal insufficiency may be due to the influence of dissection on kidney perfusion or the patient’s preoperative renal function. Acute renal failure is one of the common complications after TAAD operation, with an incidence rate ranging from 14 to 44% [
33,
34]. Renal insufficiency can cause internal environment disorder, accumulation of toxic substances or inflammatory media, and aggravate tissue edema and brain edema. In addition, the disturbance of electrolyte and acid–base balance can directly affect the recovery of brain metabolism, further increasing the possibility of brain injury [
35]. Therefore, renal protection in patients with TAAD is very important. Special attention should be paid to patients with renal insufficiency before surgery. Moreover, renal function monitoring should be strengthened after surgery. Once renal function deteriorates, hemofiltration therapy should be performed immediately to prevent irreversible damage to the whole body’s organs caused by metabolites and toxins.
CPB duration was associated with a high risk of POD in patients with TAAD. Liu et al. [
15] pointed out that longer CPB durations lead to the release of more inflammatory mediators; this phenomenon can make the cerebral blood vessels contract, eventually inhibit cerebral blood flow, and impair brain function. Prolonged CPB may cause severe pulmonary complications, such as atelectasis, respiratory distress, and hypoxemia; it may also affect the blood supply to brain tissue and induce delirium [
36]. On the one hand, the operation technique should be improved, CPB duration should be shortened, and the blood oxygen supply to the brain should be sufficient. On the other hand, postoperative monitoring should evaluate lung ventilation tolerance timely. Moreover, mechanical-assisted ventilation should be given when necessary to maintain the stability of ventilator parameters and hemodynamics of patients and avoid delirium induced by body ischemia and hypoxia.
This study found that longer operation time was one of the risk factors for POD in TAAD patients. Mu et al. [
26] showed that the risk of delirium increased by 36% every hour of prolonged operation. Prolongation of operation time can extend anesthesia time correspondingly. Fentanyl, propofol and other anesthetic drugs act on cholinergic neuronal receptors for a long time, forming inhibition of the cholinergic nerve effect and easily causing delirium [
37].
Mechanical ventilation was a risk factor for POD in patients with TAAD. Ely et al. [
37] showed that delirium may occur in patients receiving mechanical ventilation; this finding is consistent with the present study. According to earlier research [
38,
39], delirium occurred 20%–50% of the time in patients who did not receive mechanical ventilation and 60%–80% of the time in those who did. Delirium is an independent risk factor for offline difficulties and leads to prolonged mechanical ventilation [
40]. Therefore, a cluster care plan, including daily wake-up and early functional exercise, can be developed to shorten the time of mechanical ventilation as much as possible to reduce the delirium occurrence further.
The results of this study showed that the APACHE II score was closely related to the POD occurrence in TAAD patients. This finding is consistent with the research conducted by Pei et al. [
41]. The APACHE II score is a widely used and authoritative scoring system to evaluate disease severity. The severity of the patient's condition is inversely correlated with their APACHE II score. As the severity of a patient's condition increases, the length of their stay in the ICU after surgery also increases. During the postoperative stay in ICU, patients not only suffered from physical discomfort but also lacked the companionship of their families. Their anxiety and panic increased, leading to delirium.
Electrolyte disturbance was identified as a risk factor for POD in patients with TAAD. Xing et al. [
42] pointed out that metabolic alkalosis affects the central nervous system, causing agitation, insanity and other manifestations. Patients with metabolic acidosis experience not only the effects on the central nervous system but also ion imbalance, thereby weakening heart contraction, decreasing the effective blood volume, and worsening brain dysfunction. Therefore, medical staff should actively correct patients’ acid–base imbalance and electrolyte disturbance to maintain the homeostasis of patients’ internal environment.
Hypoxemia was closely related to POD in TAAD patients. In patients with hypoxemia, the body’s oxygen consumption and supply are unbalanced. Moreover, the metabolic mode of brain cells changes easily under the hypoxia state, leading to nerve cell damage and brain edema. Chronic severe cerebral hypoxia can also affect acetylcholine levels, the electrical activity of brain tissue, sleep patterns and memory; it can also quickly result in delirium [
43]. Therefore, medical staff should pay attention to the oxygen supply of TAAD patients after the operation and provide oxygen therapy to patients with hypoxemia after the operation to improve the brain oxygen supply and reduce the incidence of POD.
Limitation
This study encountered some limitations. At first, the studies included had lower quality than randomized controlled trials. The majority of them were retrospective studies, which could have selection bias. Secondly, a comprehensive study of the elements that the risk of POD in TAAD patients was hampered by the minimal number of studies that could be included in the meta-analysis. Thirdly, the included studies were Chinese and English literature. The works in the literature meeting the inclusion criteria were all from Chinese regional studies, indicating some publication bias. At present, research- and evidence-based medicine must fully understand the risk factors for delirium following TAAD, because the evidence in this area is currently insufficient.
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