Perioperative dynamic changes of systemic inflammatory response, gut injury, and hypoxemia in patients with acute type-A aortic dissection: an observational case-control study

Background: The details regarding the pathogenesis of hypoxemia in the presence of acute type-A aortic dissection (ATAAD) remains to be fully elucidated. In this study, we investigated the dynamic changes in systemic inflammatory response, gut injury, hypoxemia, and succinate levels in patients with ATAAD and their impact on perioperative hypoxemia.

Methods: We conducted a single-center, observational, case-control study that enrolled 18 patients with ATAAD who underwent emergency total arch repair (TAR) combined with frozen elephant trunk (FET) procedure under hypothermic lower-body circulatory arrest and antegrade cerebral perfusion. White blood cell (WBC) count, interleukin (IL)6, IL8, tumor necrosis factor α (TNFα), diamine oxidase (DAO), intestinal fatty-acid-binding protein (iFABP), peptidoglycan (PGN), and succinate were assessed preoperatively and 12, 24, and 48 hours after operation. The PaO₂/FiO₂ ratios were evaluated preoperatively and 4, 8, and 12 hours after operation. These variables were compared between different time points. Correlation analyses and multivariate linear regression were performed to evaluate the variables’ impact on 12-hour postoperative hypoxemia.

Results: Compared to controls, patients with ATAAD had a significantly higher preoperative WBC count [(12.18±4.50)×10⁹/L vs. (3.73±1.05)×10⁹/L; P<0.001], IL6 (129.31±12.86 vs. 114.22±14.11 pg/mL; P=0.002), IL8 (147.57±16.03 vs. 127.56±20.23 pg/mL; P=0.002), TNFα (59.29±6.90 vs. 40.51±7.53 pg/mL; P<0.001), DAO activity (17.94±1.54 vs. 13.32±1.82 U/L; P<0.001), and succinate (235.92±48.09 vs. 106.95±27.63 µM; P<0.001) but a lower PaO₂/FiO₂. In patients with ATAAD, postoperative levels of IL6, IL8, TNFα, DAO, iFABP, and PGN were significantly elevated compared to preoperative levels, while the PaO₂/FiO₂ ratio decreased significantly from the preoperative levels. Succinate levels peaked prior to the operation and remained elevated at both the 12- and 24-hour postoperative time points. PGN, iFABP, succinate, and lowest rectal temperature during cardiopulmonary bypass were the risk factors for hypoxemia at 12 hours’ postoperation.

Conclusions: Systemic inflammatory response, gut injury, and hypoxemia had already occurred preoperatively in patients with ATAAD and exacerbated postoperatively following TAR combined with FET procedure under hypothermic lower-body circulatory arrest and antegrade cerebral perfusion. Succinate may play a pivotal role in the development of hypoxemia in patients with ATAAD.

Keywords: Type A aortic dissection; systemic inflammatory response; hypoxemia; gut injury; succinate

 

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Key findings

• In this study, it was found that compared to controls, patients with acute type-A aortic dissection (ATAAD) had significantly higher preoperative white blood cell count, interleukin (IL)6, IL8, tumor necrosis factor α (TNFα), diamine oxidase (DAO), intestinal fatty-acid-binding protein (iFABP), and peptidoglycan (PGN) but a lower PaO₂/FiO₂ ratio. In patients with ATAAD, postoperative IL6, IL8, TNFα, DAO, iFABP, and PGN were significantly increased compared to preoperative levels, while PaO₂/FiO₂ ratio was further decreased. Elevated level of succinate persisted from preoperation to the 12- and 24-hour postoperative time points. PGN, iFABP, succinate, and the lowest rectal temperature during cardiopulmonary bypass were identified as the risk factors for postoperative hypoxemia.

What is known and what is new?

• In previous studies, it was reported that systemic inflammatory response, gut injury, and hypoxemia developed significantly in patients with ATAAD.

• In this study, we investigated the dynamic changes in systemic inflammatory response, gut injury, hypoxemia, and succinate level in patients with ATAAD and their impact on postoperative hypoxemia.

What is the implication, and what should change now?

• Our findings suggest that systemic inflammatory responses, gut injury, and hypoxemia increasingly intensified from preoperation to postoperation following total aortic arch repair combined with frozen elephant trunk procedure under hypothermic circulatory arrest and antegrade cerebral perfusion in patients with ATAAD. Succinate might be implicated in the exacerbation of systemic inflammatory responses and hypoxemia. Our results might be helpful in optimizing the therapeutic strategies for the attenuation of ATAAD-related systemic inflammatory responses in terms of intestinal barrier function and the succinate pathway.