This study aimed to analyze the incidence and risk factors of POD in patients with AAD who underwent novel triple-branched stent graft implantation. A total of 280 cases of AAD patients were enrolled in this research. There were 106 patients were diagnosed with delirium among them, and the incidence of delirium was 37.86%. In this research, we found that APACHE-II score > 20, types of analgesics and sedatives, and hypoxemia were independent risk factors for POD, and the non-manual worker was a protective factor for POD. At the same time, we did not find that aortic cross-clamping time and CPB time affected POD after AAD.
In the past 10 years, many studies have investigated the relationship between work and cognitive complexity. Marengoni et al.[15] and Smyth et al.[16] have shown that people who engage in physical work are more likely to have a risk of cognitive decline and dementia. Grzywacz et al.[17] found that work complexity was positively correlated with the cognitive function of episodic memory, executive function, and self-evaluation ability. The results of this research revealed that the non-manual workers in the delirium group after AAD were significantly less than those in the non-delirium group, and the results of multivariate Cox regression analysis showed that compared with the manual workers, the risk of delirium after the non-manual workers (AHR = .554; P = .015) was reduced. A variety of theories suggest that the nature of work may affect the cognitive function of the brain, among which the recognized cognitive reserve hypothesis indicates that the cognitive stimulation can increase the capacity of neurons, thus promoting the development of cognitive reserve [18]. For those who have been engaged in non-manual work for a long time, environmental stimulation may increase the level of neurotrophins available in brain tissue, protect or repair existing neurons, promote the development of nerves, and the incidence of neurological diseases will be relatively low [18].
Sedative and analgesic drugs work extensively on the central nervous system, including the nerve cell membrane, neurotransmitters, cerebral metabolism, and so on [19]. The main function of the central muscarine cholinergic system is to maintain cognitive function, while a variety of sedative and analgesic drugs act on the central alkaloid receptor [20]. Our study shows that the more analgesic and sedative drugs, the higher the risk of postoperative delirium. Related researches have indicated that the use of analgesics and sedatives is an independent risk factor for delirium after heart surgery. Pandharipande et al.[21] discovered that there was a positive correlation between benzodiazepines and the occurrence of delirium, and the incidence of delirium increased by 20% for every 1mg increase of benzodiazepines. At the same time, the latest DAS-2015 recommendation [22] suggested avoiding benzodiazepines as far as possible, because benzodiazepines are easy to induce deep sedation, induced amnesia, and other side effects. Besides, commonly used opioid analgesics such as morphine can antagonize M1, M2, and M3 receptors at clinical doses [20]. In summary, the types of sedative and analgesic drugs should be reasonably selected according to the patient's condition in clinical work.
According to reports, the incidence of hypoxemia after AD is 20.4%-49.5% [23]. Kazmierski et al. [23] indicated that postoperative hypoxemia (PaO2 < 60mmHg) was an independent risk factor for delirium after cardiac surgery. In this research, we found that the incidence of hypoxemia during and after AD surgery was 24.29%. Multivariate Cox regression analysis showed that hypoxemia increased the risk of delirium (AHR, 1.846; P < .001). AAD patients have accumulated blood and fluid in their chest cavity, and most of them need to undergo surgery under hypothermic circulatory arrest. Therefore, patients are prone to acute lung injury after surgery. Acute lung injury can lead to increased permeability of pulmonary vascular bed, pulmonary interstitial and alveolar edema, alveolar collapse, severe imbalance of ventilation/blood flow ratio, and eventually severe hypoxemia [24]. At the same time, hypoxemia can inhibit the synthesis of acetyl coenzyme A, acetylcholine, and glutamic acid in the citric acid cycle, resulting in decreased brain activity of cholinergic, which ultimately leads to an increased risk of delirium [13]. In addition, studies have shown that hypoxemia and mechanical ventilation time are interrelated. The more severe hypoxemia is, the longer mechanical ventilation time will be, and the risk of POD is increased.
The longer the duration of CPB, the greater the possibility of brain injury[25]. Surface contact between blood and CPB instrument can induce SIRS, which may be involved in the occurrence of delirium after operation through C-reactive protein, IL-1, and IL-10. Liu et al.[11] found that surgery duration (OR = 3.21; P = .002) was risk factors for POD. They speculated that prolonged surgery can lead to wider use of anesthetic drugs, increased blood transfusion, or the disturbance of electrolytes or acid-base balance. CPB time (OR = 1.360; P = .028) was also associated with a higher risk of POD. Prolonged CPB increases the release of inflammatory mediators, which can cause cerebral vasoconstriction, thereby inhibiting cerebral blood flow and changing brain function. However, none of our studies found that operative time and CPB time had an effect on POD. Shi et al.[10] and Liu et al.[11] found that the surgical methods were all Sun's surgery, and this study was a three-branch stent surgery. By comparison, the operation time of delirium group was 288.5 (250.8, 334.3) and that of the non-delirium group was 285.0 (249.5, 333.0), which was 200 minutes shorter than those of Shi et al. [10] and Liu et al. [11] and the CPB time was 40-100 minutes shorter.
Our study was a single-center observational study, and larger sample size and multicenter trials are needed to determine risk factors for delirium after AAD surgery. We only evaluated delirium in ICU patients without long-term follow-up. The effect of dexmedetomidine on delirium was not discussed in this study and will be further explored in future studies.