Hypoxemia refers to a pathological state in which the arterial partial pressure of oxygen (PaO₂) is lower than normal levels due to an insufficient oxygen content in the blood. The mechanism through which hypoxemia develops is mainly related to damage to the alveolar epithelium and microvascular endothelial cells, which can reduce oxygen partial pressure and oxygen saturation. The diagnostic criteria for hypoxemia refer to the Berlin criteria for acute respiratory distress syndrome and literature research [3, 6], specifically an oxygen index $\le$200 mmHg.

The pulmonary pathophysiological alterations induced by chronic tobacco smoke exposure arise from complex mechanisms. Cigarette-derived toxicants, including polycyclic aromatic hydrocarbons, carbon monoxide, and reactive oxygen species (ROS), directly induce apoptosis in airway epithelial cells and initiate neutrophilic inflammation. This process is mediated through a crosstalk between macrophages and T lymphocytes, characterized by elevated interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-$\alpha$) levels, which perpetuate a proinflammatory microenvironment [12]. Long-term smoking also leads to structural changes in the airway walls, including smooth muscle proliferation, fibrosis, and goblet cell hyperplasia, resulting in airway wall thickening and lumen narrowing, causing airflow limitations [13]. Additionally, fibrosis and stenosis of small airways increase airway resistance, particularly during exhalation, significantly affecting lung function [14]. Furthermore, smoking inhibits ciliary motor function and reduces mucus clearance, thereby increasing the risk of respiratory infections [15]. Numerous studies have confirmed that a history of smoking is an independent risk factor for postoperative hypoxemia [8, 16, 17]. As shown in Table 1.

Obesity, defined as a body mass index (BMI) $>$30 kg/m², represents an important risk factor for postoperative hypoxemia [9, 18]. In addition to serving as an energy storage organ, the adipose tissue in obese individuals secretes various inflammatory factors (such as TNF-$\alpha$ and IL-6) and adipokines (such as leptin and adiponectin), which contribute to a systemic inflammatory response that adversely affects lung function and gas exchange [19]. Meanwhile, fat accumulation in the chest wall and abdomen of obese individuals reduces chest wall compliance and limits diaphragm movement, thereby increasing respiratory work, causing postoperative atelectasis, disrupting the ventilation-to-blood flow ratio, and raising the incidence of hypoxemia [20]. Furthermore, the lung volume and functional residual capacity (FRC) in obese individuals are often reduced, especially in the supine position, while alveolar atrophy exacerbates gas exchange disorders [21]. As shown in Table 1. Obesity is frequently associated with metabolic syndrome, hypertension, diabetes, and cardiovascular diseases, all of which increase the likelihood of hypoxemia. Cardiovascular conditions in obese patients, such as coronary heart disease and heart failure, may reduce cardiac output and affect oxygen delivery and tissue oxygenation [22]. Studies indicate that the incidence of postoperative pneumonia in obese patients is significantly higher than in non-obese patients, possibly due to impaired immune function and decreased clearance of respiratory secretions [23]. Additionally, obese patients typically require prolonged mechanical ventilation support after surgery, heightening the risk of ventilator-associated lung injury (VILI) and hypoxemia [24].

The inflammatory response plays a crucial role in the pathological process of ATAAD. When AD occurs, an intimal tear triggers local inflammatory reactions, which subsequently evoke systemic inflammatory responses, including the release of cytokines and other inflammatory mediators. Studies have shown that the levels of inflammatory markers, such as C-reactive protein (CRP), IL-6, and TNF-$\alpha$, in the serum of TAAD patients are significantly elevated and are closely associated with the severity and prognosis of the disease [25]. Endothelial cells serve as a critical barrier for maintaining vascular permeability. Inflammatory mediators, such as TNF-$\alpha$ and IL-1$\beta$, reduce the expression of connexins between endothelial cells, including tight junction proteins, and increase vascular permeability by activating signaling pathways, including NF-$\kappa$B [26]. This increased permeability allows for the infiltration of plasma proteins and fluid into the alveolar space, resulting in pulmonary edema and impaired gas exchange. As shown in Table 1.

Renal insufficiency not only impairs the excretory function of the kidney but also exacerbates the systemic inflammatory response through various mechanisms, thereby increasing the risk of postoperative hypoxemia [27]. The accumulation of metabolic waste products, such as urea, creatinine, and uric acid, in patients with renal insufficiency activates the inflammatory signaling pathway, NF-$\kappa$B, promoting the release of inflammatory mediators, including TNF-$\alpha$, IL-6, and IL-1$\beta$, which contribute to a systemic inflammatory response. In addition to damaging the kidneys, this inflammatory reaction also harms lung tissue, resulting in increased permeability of pulmonary capillary endothelial cells, which can lead to pulmonary edema and disrupted ventilation-to-blood flow ratios [28]. Furthermore, patients with renal insufficiency often experience acid–base imbalances, electrolyte disturbances, and symptoms such as metabolic acidosis and hyperkalemia. Subsequently, metabolic acidosis can reduce the oxygen affinity of hemoglobin, impairing oxygen transport and tissue oxygenation. Elevated serum potassium levels may cause arrhythmias, further diminishing cardiac output and oxygen delivery. These metabolic disorders pose significant risks for patients following TAAD surgery, potentially exacerbating the incidence of hypoxemia [29]. As shown in Table 1. Additionally, decreased antioxidant capacity in patients with renal insufficiency leads to excessive accumulation of ROS in the body, which can directly damage lung tissue cells and further activate inflammatory signaling pathways, creating a negative feedback cycle. Studies have shown that oxidative stress plays a critical role in the development of lung injury and hypoxemia following TAAD surgery [11].

Patients with preoperative hypoxemia often exhibit decreased lung compliance and symptoms such as ventilation-to-blood flow (V/Q) imbalance. Meanwhile, V/Q imbalance aggravates hypoxemia and contributes to alveolar ventilation insufficiency. Studies have shown that patients with preoperative hypoxemia require significantly prolonged mechanical ventilation time after surgery and are more prone to developing acute respiratory distress syndrome (ARDS) [30]. As shown in Table 1. Additionally, preoperative hypoxemia is closely associated with the exacerbation of the systemic inflammatory response. Hypoxemia activates the hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) signaling pathway, promoting the release of inflammatory mediators, such as TNF-$\alpha$, IL-6, and IL-1$\beta$, and triggering a systemic inflammatory response. This inflammatory reaction not only damages lung tissue but may also affect other organs, leading to multiple organ dysfunction syndrome (MODS). Studies have indicated that the levels of inflammatory markers in patients with preoperative hypoxemia are significantly elevated and positively correlate with postoperative severity [31]. Furthermore, preoperative hypoxemia can impair the immune function of the body. Hypoxic conditions exert an inhibitory effect on the function of immune cells, such as macrophages and neutrophils, thereby reducing their ability to eliminate pathogens and increasing the risk of postoperative infections. Infections not only exacerbate lung injury but also worsen oxygen delivery, creating a negative feedback cycle. Studies have shown that the incidence of postoperative pneumonia in patients with preoperative hypoxemia is significantly higher than in those without hypoxemia [32].

OSAS is a common sleep-disordered breathing condition characterized by recurrent apnea or hypopnea during sleep, resulting from partial or complete obstruction of the upper airway. These respiratory events can lead to sympathetic activation, increased oxidative stress, and an augmented systemic inflammatory response, resulting in intermittent hypoxemia and hypercapnia. These pathophysiological changes not only affect cardiovascular function but also impair lung function, significantly increasing the risk of hypoxemia following TAAD surgery [33]. Intermittent hypoxemia in patients with OSAS during sleep can cause periodic elevations in pulmonary artery pressure, potentially leading to chronic pulmonary hypertension over time. Subsequently, pulmonary hypertension increases the workload on the right side of the heart, which can lead to right heart dysfunction, ultimately affecting left heart function and cardiac output. Decreased cardiac function can further exacerbate postoperative hypoxemia, particularly in the context of TAAD surgery, where the cardiopulmonary function of patients undergoing surgery and cardiopulmonary bypass is already compromised [34]. As shown in Table 1. Additionally, intermittent hypoxemia in OSAS patients can induce oxidative stress and inflammatory responses. Increased production of ROS under hypoxic conditions leads to direct damage to lung tissue cells and activates the inflammatory signaling pathway, including NF-$\kappa$B, promoting the release of inflammatory mediators, such as TNF-$\alpha$ and IL-6. These mediators can further damage the microvascular endothelial cells in the lungs, and increased vascular permeability contributes to pulmonary edema and disrupted ventilation-to-blood flow ratios, thereby aggravating postoperative hypoxemia [35]. Patients with OSAS often experience increased upper airway resistance and elevated respiratory workload, resulting in increased intrathoracic negative pressure and fatigue of the respiratory muscles. Patients after TAAD surgery may require mechanical ventilation support; meanwhile, those with OSAS are at greater risk of developing VILI and atelectasis, further heightening the risk of hypoxemia [36].

Massive blood transfusions (defined as the transfusion of $\ge$10 units of red blood cells within 24 hours or more than 50% of the total blood volume of the patient in a short period) are closely associated with postoperative hypoxemia [37]. Biologically active substances, such as anti-white blood cell antibodies, lipid mediators, and cytokines, which are released during blood transfusion, can activate pulmonary vascular endothelial cells and neutrophils, leading to an inflammatory response. During blood transfusion, activated neutrophils from stored blood adhere to the pulmonary microvascular wall, releasing proteases and ROS, which compromise the alveolar–microvascular barrier and cause non-cardiogenic pulmonary edema. A significant cause of postoperative hypoxemia is TRALI, characterized by clinical manifestations such as acute dyspnea, hypoxemia, and exudative changes on chest imaging [38]. As shown in Table 1. Additionally, microparticles, cell debris, and fibrinogen, which gradually accumulate during storage, can form microthrombi in the pulmonary microvascular network after infusion. These microthrombi not only obstruct pulmonary microvessels, exacerbating the imbalance of ventilation-to-blood flow ratios, but also release proinflammatory factors, such as HMGB1 and histamine, which further damage lung tissue. Studies have shown that the incidence of postoperative pneumonia in patients receiving blood transfusions increases by 3.4 times, with a significant rise in pneumonia incidence for each additional unit of red blood cell transfusion [39].

CPB, an essential technique in ATAAD surgery, provides a blood-free field and a stable hemodynamic environment by temporarily replacing cardiopulmonary function with a mechanical device. However, the prolonged use of CPB has significantly increased the incidence of postoperative hypoxemia [40]. During CPB, blood comes into contact with the artificial conduit, triggering the activation of the complement system and the release of numerous inflammatory mediators from white blood cells, including TNF-$\alpha$, IL-6, and IL-8. These mediators not only directly damage lung tissue but also promote the adhesion and infiltration of white blood cells in the pulmonary microvessels. Increased levels of adhesion molecules (such as ICAM-1 and VCAM-1) contribute to worsening lung injury. Meanwhile, studies have shown that the duration of CPB is positively correlated with the levels of postoperative inflammatory markers, such as CRP and procalcitonin (PCT), while the intensity of the inflammatory response is closely related to the severity of hypoxemia [41]. Ischemia and mechanical stretching of lung tissue during CPB reduce the synthesis and secretion of pulmonary surfactant (PS) and impair the function of alveolar type II epithelial cells. Subsequently, this reduction in PS decreases alveolar stability and increases the risk of alveolar collapse, leading to a V/Q imbalance. Prior research has demonstrated that the PS content in bronchoalveolar lavage fluid from patients after CPB surgery is significantly reduced and positively correlates with the oxygenation index (PaO₂/fraction of inspired oxygen (FiO₂)) [42]. Meanwhile, when blood flow is restored after CPB, the ischemic tissue undergoes reperfusion, producing large amounts of ROS and inflammatory mediators that further exacerbate tissue damage. Alveolar epithelial cell necrosis, increased capillary permeability, and pulmonary interstitial edema promote hypoxemia [43]. As shown in Table 1. Lung tissue is particularly sensitive to ischemia-reperfusion injury. Deep hypothermic circulatory arrest (DHCA) is a specialized technique applied during CPB. During DHCA, lung tissue experiences complete ischemia and hypoxia, remaining in a state of no ventilation for extended periods. This prolonged ischemia can result in alveolar collapse, atelectasis, and reduced lung volume, potentially causing or exacerbating V/Q imbalance and increasing the risk of postoperative hypoxemia [44]. This process is primarily manifested as lung tissue ischemia-reperfusion injury [45]. Numerous studies have shown that CPB and DHCA can exacerbate lung injury and elevate the incidence of postoperative hypoxemia in patients with ATAAD. Liu et al. [45] found that durations of DHCA exceeding 25 minutes significantly increase the risk of postoperative hypoxemia . Furthermore, several studies have confirmed that CPB and DHCA are independent risk factors for postoperative hypoxemia in patients with ATAAD [46, 47, 48, 49, 50, 51].

Age represents a significant risk factor for postoperative hypoxemia [52]. Zhang et al. [53] indicated that age is an independent predictor of early postoperative hypoxemia, with a notable increase in the incidence of hypoxemia as age rises. Additionally, the occurrence of postoperative hypoxemia is related to the time interval from the onset of TAAD to surgery. Studies have shown that delayed surgery can result in prolonged ischemia and elevated blood pressure before the operation, which may further exacerbate damage to the heart and other organs, consequently increasing the risk of postoperative complications [52, 53, 54].

Prone position positive pressure ventilation (PPV) is a crucial strategy for treating ARDS and postoperative hypoxemia [55]. By improving the uniformity of lung ventilation, prone position ventilation can reduce intrapulmonary shunting. Increased blood flow perfusion in the dorsal lung area during the prone position corresponds to enhanced ventilation, allowing for a better match of the V/Q ratio. Clinical studies have demonstrated that prone position ventilation can increase the oxygenation index (PaO₂/FiO₂) by 50% to 100%, particularly in patients with severe ARDS [56]. Additionally, prone position ventilation can reduce the risk of VILI by evenly distributing ventilation pressure, thereby minimizing local alveolar overexpansion and shear stress. As shown in Table 2. Research has shown that prone position ventilation leads to a more uniform distribution of alveolar pressure and reduces the release of markers of alveolar injury, such as IL-6 and TNF-$\alpha$, ultimately decreasing lung injury [57]. However, there is a lack of evidence-based consensus on the balance between PEEP setting and blood pressure stability (PEEP range 5–15 cmH₂O in existing studies, but no established hemodynamic guidance scheme) [58].

Nasal high-flow humidified oxygen therapy (HFNO) combined with nitric oxide (NO) inhalation is an innovative treatment strategy that effectively improves oxygenation function in patients with hypoxemia following TAAD, while reducing the duration of mechanical ventilation and hospitalization. HFNO enhances oxygen binding capacity by delivering high flow rates (up to 60 L/min) of heated and humidified oxygen. The high-flow gas helps to eliminate dead space in the nasopharynx, reducing the re-inhalation of carbon dioxide (CO₂) and increasing ventilation efficiency. Studies have shown that HFNO can reduce anatomical dead space by 30% to 40%, significantly improving oxygenation function [59]. Additionally, HFNO promotes alveolar recruitment by generating a certain level of positive airway pressure (typically 2 to 5 cmH₂O), which helps to reduce atelectasis. As shown in Table 2. Clinical studies demonstrate that HFNO can increase the oxygenation (PaO₂/FiO₂) index by 20% to 30% [60]. Meanwhile, the warming and humidification functions of HFNO also decrease airway dryness and mucus viscosity, enhancing patient tolerance, comfort, and reducing the risk of re-intubation. NO is a selective pulmonary vasodilator that increases cyclic guanosine monophosphate (cGMP) levels by activating soluble guanylate cyclase (sGC), improving the V/Q ratio. Studies have indicated that NO inhalation can increase the oxygenation index by 30% to 50% [61]. Furthermore, NO also reduces intrapulmonary shunting by raising the arterial partial pressure of oxygen (PaO₂). Clinical research has shown that NO inhalation can decrease the intrapulmonary shunt rate by 20% to 30% [62]. The combination of HFNO and NO inhalation significantly reduces postoperative mechanical ventilation time in patients with hypoxemia [58]. The two synergistically improve oxygenation: HFNC provides constant FiO₂ and reduces respiratory work, while NO selectively dilates the pulmonary vessels in the ventilation area and reduces pulmonary artery pressure [63].

Extracorporeal membrane oxygenation (ECMO) is an advanced life support technique that provides in vitro gas exchange to enhance oxygenation and improve carbon dioxide clearance in patients with severe ARDS. For patients with severe hypoxemia following TAAD, ECMO is a critical alternative when conventional mechanical ventilation fails to enhance oxygen absorption effectively. ECMO facilitates oxygenation and CO₂ removal through an extracorporeal circulation system, either replacing or partially supporting lung function. The membrane oxygenator in ECMO effectively eliminates CO₂ from the blood while delivering O₂, significantly improving the arterial PaO₂. Studies have shown that ECMO can increase the oxygenation index (PaO₂/FiO₂) by 50% to 100% [64]. As shown in Table 2. Additionally, ECMO reduces the risk of VILI by lowering the pressure and tidal volume of mechanical ventilation, thereby preventing alveolar overexpansion and shear stress. Clinical studies indicate that ECMO can decrease mechanical ventilation pressure by 30% to 40%, significantly reducing the release of lung injury markers, such as IL-6 and TNF-$\alpha$ [65]. Furthermore, ECMO can provide cardiopulmonary support for patients with cardiac insufficiency by enhancing cardiac output and tissue perfusion in the veno-arterial (VA) mode [66].

Drugs such as ulinastatin (UTI) and methylprednisolone have significant effects on alleviating inflammatory responses and improving lung function, particularly in the treatment of hypoxemia following TAAD. UTI is a broad-spectrum protease inhibitor with anti-inflammatory, antioxidant, and cytoprotective properties. UTI reduces the release of inflammatory mediators by inhibiting signaling pathways such as NF-$\kappa$B, IL-6, and IL-1$\beta$, thereby alleviating systemic inflammatory responses and lung tissue damage [67]. Methylprednisolone is a potent anti-inflammatory and immunosuppressive glucocorticoid that reduces the synthesis and release of inflammatory mediators by inhibiting the NF-$\kappa$B and AP-1 signaling pathways, subsequently diminishing the inflammatory response in lung tissue. Numerous clinical studies have demonstrated that UTI and methylprednisolone are effective in treating hypoxemia after TAAD. A study involving 120 patients following TAAD surgery showed that the oxygenation index in the UTI treatment group was significantly higher than that in the control group (PaO₂/FiO₂: 280 vs. 220 mmHg). Additionally, the duration of mechanical ventilation was reduced by an average of 2.5 days [68]. As shown in Table 2. However, the existing randomized clinical trial (RCT) dose range is too wide (300,000-1 million IU/day). Moreover, there is a lack of phase III dose exploration trials, and no dynamic adjustments are combined with biomarkers (such as the decline in IL-8 levels). The effects of different doses of ulinastatin, the timing of hormone use (preoperative vs. CPB), and the combination of ventilation strategies on hypoxemia should be further investigated.

Hypoxemia is a common serious complication after ATAAD, and its occurrence is related to various risk factors, including smoking history, obesity, inflammatory response, preoperative renal insufficiency, preoperative hypoxemia, obstructive sleep apnea syndrome, age, CPB, DHCA time, and intraoperative blood transfusion. There is a lack of standardized regimen for UTI dose and mechanical ventilation parameters in treatment, no clinical transformation of key biomarkers, and a lack of dynamic data on long-term lung function and neurological prognosis. Future research should focus on conducting biomarker-driven precision intervention trials (such as stratified RCT to verify the optimal dose of ulinastatin); developing a dynamic prediction model for integrating intraoperative real-time monitoring data; meanwhile, we should be simultaneously incorporating interdisciplinary technologies and multi-center collaborative networks to build a closed-loop system of “monitoring-warning-intervention” to promote the transformation of clinical practice to a dynamic and precise model. Hypoxemia not only prolongs the mechanical ventilation and ICU treatment times of patients, but also significantly reduces their survival rate. Therefore, for ATAAD patients with risk factors of postoperative hypoxemia, comprehensive preoperative evaluation and perioperative management should be performed, and appropriate intervention measures should be taken to reduce the incidence of postoperative hypoxemia.