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Efficacy of sivelestat in alleviating postoperative pulmonary injury in patients with acute aortic dissection undergoing total arch replacement: a retrospective cohort study

BMC Cardiovascular Disorders volumeĀ 25, ArticleĀ number:Ā 121 (2025) Cite this article

Abstract

Objective

Sivelestat may reduce postoperative pulmonary injury after total arch replacement (TAR). This study aimed to evaluate whether the preoperative PaO2/FiO2 (P/F) ratio affects the efficacy of sivelestat in reducing postoperative pulmonary injury in patients with acute aortic dissection (AAD) who underwent TAR using deep hypothermic circulatory arrest (DHCA).

Methods

Data of patients with AAD who underwent TAR using DHCA in a tertiary hospital between February 1, 2022, and December 30, 2022, were retrospectively reviewed. The patients were divided into the sivelestat and control groups. Three subgroup analyses were performed based on the postoperative P/F ratio. The primary clinical outcomes were assessed to determine the efficacy and safety of sivelestat in managing postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass.

Results

A total of 187 patients were included, with 95 in the sivelestat group and 92 in the control group. No significant differences were found in the clinical variables between the two groups (all Pā€‰>ā€‰0.05), except for some improvements in the inflammatory biomarker levels (including white blood cell count, neutrophil count, and C-reactive protein). Subgroup analysis revealed that sivelestat treatment significantly increased the P/F ratio on the 4th day and 3rd day after TAR in patients with mild lung injury (Pā€‰=ā€‰0.02) and moderate lung injury (Pā€‰=ā€‰0.03), respectively. Additionally, sivelestat reduced the levels of several postoperative inflammatory biomarkers in both subgroups.

Conclusions

Among patients with AAD with mild or moderate preoperative lung injury, defined by a low P/F ratio, sivelestat significantly improved the postoperative P/F ratio and attenuated inflammatory responses after TAR. These findings suggest an important avenue for further research.

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Introduction

Acute aortic dissection (AAD) is one of the most fatal cardiovascular emergencies, with an in-hospital mortality rate of 22% over the past decade [1, 2]. According to the current guidelines, the primary treatment for AAD is surgery using cardiopulmonary bypass (CPB). CPB is a clinical support technology that plays a dual role in cardiac surgery. It enables cardiac surgeons to perform complex surgeries, such as those involving the heart, ascending aorta, or aortic arch, by providing a blood-free, stable operative field. This is particularly important for patients with AAD who may require total arch replacement (TAR) with deep hypothermic circulatory arrest (DHCA). Moreover, CPB is essential for maintaining patient survival during surgery. By assuming the functions of the heart and lungs, CPB ensures continuous perfusion of oxygenated blood to vital organs during surgery, reducing the risk of organ damage and enhancing the likelihood of a successful surgical outcome. Owing to the inherent complexity of CPB and related cardiac procedures [3, 4], various postoperative complications, including pulmonary injury, commonly occur [5, 6], particularly in patients with AAD who underwent TAR using DHCA. Previous clinical studies have found that 30.0ā€“50.0% of patients with AAD develop postoperative pulmonary injury, primarily characterized by respiratory distress and hypoxemia [7]. This condition can progress to acute respiratory distress syndrome (ARDS), significantly affecting the prognosis of patients with AAD [8, 9]. Therefore, implementing therapeutic measures to prevent pulmonary injury after TAR is crucial.

Several studies have investigated strategies to protect against CPB-induced lung injury. Rhee et al. demonstrated that high-dose ulinastatin improved pulmonary function after CPB in patients undergoing aortic valve surgery [10]. Furthermore, Petak et al. found that dopamine effectively facilitated postoperative respiratory management in patients undergoing TAR using CPB [11]. Sivelestat, a well-known neutrophil elastase (NE) inhibitor developed and manufactured in Japan, has been used to treat acute lung injury, including ARDS, in patients with systemic inflammatory response syndrome [12,13,14]. Sivirastat is clinically used to treat acute lung injury by inhibiting NE activity [15] and was rapidly marketed in China during the coronavirus disease 2019 pandemic in 2020. As a potent NE inhibitor, sivelestat has been shown to reduce the release of inflammatory mediators in pulmonary tissue, thereby alleviating pulmonary injury and improving respiratory function [16, 17]. Recent clinical studies have shown that sivelestat improves pulmonary injury after TAR in patients with AAD [16, 18]. Furthermore, a reduction in the PaO2/FiO2 (P/F) ratio in AAD is closely correlated with the severity of aortic injury [19]. However, whether the preoperative P/F ratio affects the efficacy of sivelestat in preventing postoperative pulmonary injury remains unknown. Therefore, this study aimed to assess the efficacy of sivelestat in preventing postoperative pulmonary injury in patients with AAD who underwent TAR under DHCA based on different preoperative P/F ratios.

Materials and methods

Study design and participants

This single-center, retrospective cohort study was conducted in accordance with the Declaration of Helsinki and approved by the Ethical Committee of Xijing Hospital (KY20242093-C-1). The requirement for written consent was waived owing to the retrospective nature of the study. From February 1, 2022, to December 30, 2022, consecutive patients with AAD who underwent TAR using DHCA at a tertiary hospital were enrolled. Patients (1) aged 18ā€“70 years, (2) with AAD, and (3) who have undergone TAR were analyzed. By contrast, patients (1) with a history of end-stage chronic obstructive pulmonary disease or chronic interstitial pulmonary disease, (2) with a history of end-stage renal disease requiring dialysis, (3) with a history of sivelestat use prior to admission, (4) who were pregnant, (5) who died within 48Ā h after surgery, and (6) with incomplete data were excluded.

Study methods

The decision to administer sivelestat was based on its potential therapeutic effect in preventing pulmonary injury following cardiac surgery in patients with AAD undergoing TAR using DHCA. Previous studies have demonstrated sivelestatā€™s ability to reduce pulmonary inflammation and improve respiratory function [16, 18]. The control group received conventional treatment without sivelestat. The sivelestat group received a continuous infusion of sivelestat after the induction of anesthesia. The initial dose (4.8Ā mg/kg) was diluted with 50Ā ml 0.9% sodium chloride solution and administered intravenously at a rate of 0.2Ā mg/kg/h for 48Ā h after intensive care unit (ICU) admission.

Operative and anesthesia techniques

All patients with type A AAD were admitted to the cardiac ICU. Anti-inflammatory drugs were not administered prior to TAR. After TAR, all patients were transferred back to the ICU and received mechanical ventilation (MV). The tidal volume was calculated using the formula 8ā€“10Ā ml/kg of standard body weight, and positive end-expiratory pressure (PEEP) was maintained at less than 7.5 mmHg. The criteria for ventilator weaning were as follows: (1) clear consciousness, recovery from spontaneous breathing, good cough force, effective airway clearance, and the absence of rapid or strenuous breathing; (2) stable circulation; (3) postoperative drainage of <ā€‰50Ā ml/h or thin drainage fluid characteristics; and (4) stable homeostasis. After surgery, flurbiprofen axetil (a non-steroidal anti-inflammatory drug) was used for analgesia, whereas dexmedetomidine was used for sedation. This protocol was consistently applied in both the sivelestat and control groups.

Definition and data collection

The preoperative P/F ratios in the control and sivelestat groups were divided into subgroups according to the Berlin definition of ARDS [20]. The Berlin definition classifies ARDS based on the P/F ratio measured within 7 days after a known clinical insult, with the patient receiving a minimum of 5Ā cm H2O PEEP. In our study, the following P/F ratio-based classifications were used: moderate lung injury was defined as a P/F ratio of 100 mmHg to ā‰¤ā€‰200 mmHg, mild lung injury as a P/F ratio of 200 mmHg to ā‰¤ā€‰300 mmHg, and normal as a P/F ratio of >ā€‰300 mmHg. These classifications were used to assess the preoperative pulmonary status of the patients and analyze the impact of sivelestat on different levels of preoperative lung injury. The P/F ratio of patients before or after TAR was determined based on the lowest P/F ratio on that day. In this study, patients were followed up for 26.3ā€‰Ā±ā€‰7.6 (median: 30, interquartile range (IQR): 28ā€“30) days, with no patient lost to follow-up. Data on the P/F ratio, white blood cell (WBC) count, neutrophil ratio, absolute neutrophil count (ANC), C-reactive protein (CRP), procalcitonin (PCT), total protein (TP), interleukin-6 (IL-6), and tumor necrosis factor-Ī± levels on postoperative day 1 (POD1), POD2, POD3, POD4, and POD5 were collected from the electronic medical record system.

The primary clinical outcomes included 30-day mortality and use of extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT), and intra-aortic balloon pump (IABP). The secondary clinical outcomes included the incidence of pneumonia, high arterial lactate levels (>ā€‰2 mmol/L) lasting for more than 48Ā h, length of ICU stay, length of hospital stay (LOS), duration of MV, incidence of secondary MV, and postoperative thoracic drainage.

Statistical analysis

Statistical analyses were performed using the Statistical Package for the Social Sciences software (version 24). Continuous data were expressed as the means and standard deviations when normally distributed, or as medians and IQRs when not normally distributed. The Shapiroā€“Wilk test was used to assess normality. Categorical data were expressed as frequencies and percentages. The chi-square test or Fisherā€™s exact test was used to compare categorical data between the two groups. Studentā€™s t-test (normal distribution) or Mann-Whitney U test (non-normal distribution) was used to compare continuous variables. A small amount of missing data was statistically interpolated using mean interpolation. A two-sided Pā€‰value of <ā€‰0.05 was considered significant.

Results

Comparison of baseline characteristics and postoperative outcomes between the sivelestat and control groups

From February 1, 2022, to December 30, 2022, a total of 187 patients (95 in the sivelestat group and 92 in the control group) were included in the study (Fig.Ā 1). The baseline data and perioperative parameters of the patients in the two groups are shown in TableĀ 1. Overall, no significant differences were observed in the baseline characteristics or medical history between the two groups (all Pā€‰>ā€‰0.05). Furthermore, no significant differences were found in 30-day mortality (Pā€‰=ā€‰0.43), ECMO use (Pā€‰=ā€‰0.67), CRRT (Pā€‰=ā€‰0.63), incidence of pneumonia (Pā€‰=ā€‰1.00), the duration of high arterial lactate levels (>ā€‰2 mmol/L for >ā€‰48Ā h) (Pā€‰=ā€‰0.53), length of ICU stay (Pā€‰=ā€‰0.84), LOS (Pā€‰=ā€‰0.34), duration of MV (Pā€‰=ā€‰0.48), incidence of secondary MV (Pā€‰=ā€‰0.44), and postoperative thoracic drainage (Pā€‰=ā€‰0.96) between the sivelestat and control groups (TableĀ 1).

Fig. 1
figure 1

Flow chart showing the participant enrollment process

Full size image
Table 1 Patients characteristics and postoperative outcomes in pre- subgroup treatment
Full size table

P/F ratio and inflammatory biomarker levels of the sivelestat and control groups within the first 5 days after TAR.

As shown in TableĀ 2, all P/F ratios within the first 5 days after TAR were comparable between the two groups (all Pā€‰>ā€‰0.05). Compared with the control group, the sivelestat group had significantly lower WBC at POD3 (Pā€‰=ā€‰0.02), ANC at POD3 (Pā€‰=ā€‰0.04) and POD4 (Pā€‰=ā€‰0.01), and CRP at POD1 (Pā€‰=ā€‰0.04). However, no significant differences were observed in other inflammatory biomarkers between the two groups (Pā€‰>ā€‰0.05).

Table 2 Comparison of lowest P/F ratio and inflammatory markers between two groups within 5 days after surgical treatment
Full size table

Characteristics of patients in different subgroups

To further investigate the efficacy of sivelestat on clinical outcomes across different baseline P/F ratios, three subgroups were analyzed. The baseline characteristics and perioperative conditions of the subgroups are shown in TableĀ 3. In all subgroup analyses, no significant differences were found in the primary and secondary clinical outcomes.

Table 3 Comparison of baseline characteristics and postoperative outcomes between sivelestat group and control group patients with normal, mild, and moderate lung injury
Full size table

Comparison of lowest P/F ratio and inflammation biomarker levels within the first 5 days after TAR between the sivelestat group and control group in different subgroups

The results of the analysis of the lowest P/F ratio and inflammatory biomarkers within the first 5 days after TAR are shown in TableĀ 4. Among patients in the normal group, no significant differences were found in the lowest P/F ratio and inflammatory biomarker levels after 5 days of TAR treatment. Nevertheless, among patients with mild lung injury, the postoperative lowest P/F ratio at POD 4 was significantly improved in the sivelestat group compared with the control group (264.44ā€‰Ā±ā€‰79.90 vs. 215.76ā€‰Ā±ā€‰49.90, Pā€‰=ā€‰0.02). Additionally, the levels of postoperative inflammatory biomarkers, including WBC count on POD1 and POD3; ANC on POD2 and POD3; and TP on POD1, POD3, and POD4, were all significantly reduced in the sivelestat group compared with the control group (all Pā€‰<ā€‰0.05). Among patients with moderate lung injury, the postoperative lowest P/F ratio on POD3 was significantly improved in the sivelestat group compared with the control group (median [IQR]: 195.83 [188.45ā€“231.52] vs. 183.71 [155.80ā€“202.98], Pā€‰=ā€‰0.03). Additionally, the levels of postoperative inflammatory biomarkers, including WBC on POD4, ANC on POD4, TP on POD4, and PCT on POD2 were all significantly reduced compared with the control group (all Pā€‰<ā€‰0.05).

Table 4 Comparison of lowest PaO2/FiO2 ratio and and inflammation biomarkers between sivelestat group and control group patients with normal, mild, and moderate lung injury
Full size table

Discussion

The prevention and treatment of lung injury after cardiac surgery under CPB in patients with AAD is widely recognized as one of the most challenging aspects of patient care in this field. Recently, many patients with AAD present with preoperative ventilatory dysfunction, which increases the risk of adverse postoperative clinical outcomes. Therefore, we designed this retrospective cohort study to classify patients with AAD into different subgroups according to the Berlin definition based on the preoperative P/F ratio. Our study demonstrated that patients with AAD who developed mild (200 to <ā€‰300) or moderate (100 to <ā€‰200) lung injury preoperatively showed significant improvements in postoperative P/F ratios following early treatment with sivelestat after TAR. Additionally, sivelestat significantly reduced the levels of ANC, WBC, and CRP in the mild and moderate lung injury subgroups, indicating that this treatment could improve postoperative inflammatory responses in patients with AAD. Our findings suggest that sivelestat may effectively improve lung injury in patients with AAD after cardiac surgery with CPB, which is consistent with the results of a previous study [18].

The occurrence of pulmonary injury in patients with AAD is often influenced by a variety of factors [20, 21]. Cardiac surgery with CPB, particularly hypothermic aortic arch replacement, is one of the most common causes of such injury and is often unavoidable in the treatment of AAD [20]. The imbalance between NE and its endogenous inhibitors is involved in the pathogenesis of pulmonary injury in patients undergoing CPB-induced cardiac surgery [20, 22]. Sivelestat, a synthetic NE-specific inhibitor, is an effective treatment for ARDS and acute lung injury associated with systemic inflammatory response [23]. In recent years, it has also been used to treat pulmonary injury after cardiac surgery in patients with AAD [11, 16, 24, 25]. The protective effects of sivelestat against lung injury caused by CPB in patients have been confirmed in several clinical studies [18, 26]. However, most of the participants included in the abovementioned clinical studies were patients with AAD undergoing cardiac surgery using CPB, regardless of their preoperative pulmonary function, which may lead to potential overuse of the drug. In this study, the laboratory results indicated that sivelestat could protect against lung injury, improve oxygenation disorders, and mitigate the inflammatory response after cardiac surgery in patients with AAD with mild and moderate pulmonary injury. However, the translation of these beneficial effects into significant improvements in all clinical outcomes, such as the duration of MV and the use of resources like transfusion requirements, IABP, and CRRT, was not as straightforward. Further research is required to fully elucidate the clinical implications of these laboratory improvements. This finding may provide a theoretical basis for the individualized use of sivelestat in clinical practice.

Clinically, the P/F ratio is a valuable tool for assessing the severity of pulmonary injury according to the Berlin definition and provides insights into patient prognosis [24]. Previous clinical studies have shown that approximately 32.2ā€“51% of patients with AAD have pulmonary injury prior to surgery, which substantially increases the risk and severity of lung injury following CPB cardiac surgery [8, 9]. Thus, the prevention and treatment of patients with AAD who developed pulmonary injury prior to surgery is a crucial strategy for reducing pulmonary injury after cardiac surgery using CPB. Although the administration of sivelestat did not lead to significant improvements in postoperative adverse events, pulmonary function, or inflammatory response levels in patients with AAD, notable improvements were observed in pulmonary function and inflammatory response were found in patients with mild or moderate preoperative lung injury based on P/F ratios. These findings emphasize the importance of pulmonary function assessment and early sivelestat treatment.

The finding that only patients with AAD with mild or moderate preoperative lung injury, as determined by the P/F ratio, benefited from sivelestat infusion after TAR is both novel and crucial in this study. Several factors may explain this phenomenon. First, the extent of underlying pulmonary inflammation and tissue damage varied depending on the preoperative P/F ratios. Patients with mild or moderate preoperative lung injury are likely to exhibit an activated inflammatory cascade, with NE being a key mediator of pulmonary injury. In these patients, sivelestat, a potent NE inhibitor, effectively interferes with the NE-mediated inflammatory processes. It also reduces the release of inflammatory mediators, thereby alleviating pulmonary inflammation and improving oxygen saturation. By contrast, patients with normal preoperative P/F ratios tend to have intact pulmonary defense systems, with lower levels of NE-related inflammatory activation. Therefore, the effect of sivelestat on these patients is less evident [27]. Second, the pulmonary microenvironment varies among patients with different preoperative P/F ratios. Factors such as immune cell distribution, cytokine levels, and endothelial function play a role. For patients with mild or moderate lung injury, a disrupted microenvironment provides more favorable conditions for sivelestat to exert its effects [28]. For example, sivelestat may regulate immune cell infiltration and activation, correct imbalances in cytokine levels, and improve endothelial function, ultimately reducing pulmonary injury and improving respiratory function.

The results of the present study present an interesting dichotomy between laboratory improvements and clinical outcomes. Although laboratory data demonstrated the potential of sivelestat to protect against lung injury and modulate the inflammatory response in patients with AAD with mild and moderate pulmonary injury, the expected significant improvements in clinical outcomes were not uniformly observed. One possible explanation for this discrepancy is the relatively small sample size of our study. A larger sample size may have been more likely to detect subtle differences in clinical outcomes that were not evident in the current analysis. Additionally, the complexity of AAD surgeries, often involving deep hypothermic circulatory arrest and TAR, along with the presence of multiple comorbidities, could introduce confounding factors that influence the clinical course. These factors may have overshadowed the beneficial effects of sivelestat on clinical outcomes. Future research with larger patient populations and better control of confounding variables is necessary to clarify the true clinical impact of sivelestat in this patient group.

Our study has some limitations. First, this was a single-center retrospective cohort study. Second, the limited sample size in each subgroup may be insufficient to observe improvements in clinically relevant outcomes and may introduce bias. Third, due to the non-normal distribution of most outcome data, including the P/F ratio, we were unable to calculate Cohenā€™s D to assess the effect size. Cohenā€™s D is commonly used under the assumption of normality, and its application to non-normal data would yield inaccurate results. Finally, treatment and selection variability cannot be avoided as the decision to administer sivelestat was made by the treating physician. Further clinical studies with a larger sample size, a multicenter design, and a robust statistical method to address potential biases are needed to confirm our findings.

Conclusion

In conclusion, sivelestat can improve the P/F ratio and significantly reduce the levels of inflammatory biomarkers in patients with AAD with mild to moderate lung injury after cardiac surgery. These findings demonstrate the potential protective effect of sivelestat against CPB-induced lung injury and its role in mitigating the inflammatory response in patients undergoing TAR.

Data availability

Availability of data and materials: The datasets generated and analysed during the current study are not publicly available due patient privacy and scales copyright but are available from the corresponding author on reasonable request.

References

  1. Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, Evangelista A, Fattori R, Suzuki T, Oh JK, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA. 2000;283(7):897ā€“903.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  2. Su IM, Huang HK, Liu PP, Hsu JY, Lin SM, Loh CH. Mortality risk from acute aortic dissection among hospital admissions during weekends and holiday season. PLoS ONE. 2021;16(9):e0255942.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  3. Malaisrie SC, Szeto WY, Halas M, Girardi LN, Coselli JS, Sundt TM 3rd, Chen EP, Fischbein MP, Gleason TG, Okita Y, et al. 2021 the American Association for Thoracic Surgery expert consensus document: surgical treatment of acute type a aortic dissection. J Thorac Cardiovasc Surg. 2021;162(3):735ā€“e758732.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  4. Gao J, Yan J, Duan Y, Yu J, Li W, Luo Z, Yu W, Xie D, Liu Z, Xiong J. Aortic arch branch-prioritized reconstruction for type A aortic dissection surgery. Front Cardiovasc Med. 2023;10:1321700.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  5. Nteliopoulos G, Nikolakopoulou Z, Chow BHN, Corless R, Nguyen B, Dimarakis I. Lung injury following cardiopulmonary bypass: a clinical update. Expert Rev Cardiovasc Ther. 2022;20(11):871ā€“80.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  6. Dong P, Xue FS, Liu SH. Identification of risk factors for acute kidney injury after pulmonary endarterectomy with cardiopulmonary bypass. J Cardiothorac Surg. 2020;15(1):99.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  7. Wang Q, Feng W, Kuang J, Wu J, Yang J, Li C, Fan R. Prediction model for postoperative severe acute lung injury in patients undergoing acute type a aortic dissection surgery. J Card Surg. 2022;37(6):1602ā€“10.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  8. Zhao X, Bie M. Preoperative acute lung injury and oxygenation impairment occurred in the patients with acute aortic dissection. BMC Cardiovasc Disord. 2022;22(1):129.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  9. Zhao X, Bie M. Predictors for the development of preoperative oxygenation impairment in acute aortic dissection in hypertensive patients. BMC Cardiovasc Disord. 2020;20(1):365.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  10. Rhee KY, Sung TY, Kim JD, Kang H, Mohamad N, Kim TY. High-dose ulinastatin improves postoperative oxygenation in patients undergoing aortic valve surgery with cardiopulmonary bypass: a retrospective study. J Int Med Res. 2018;46(3):1238ā€“48.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  11. PetĆ”k F, Balogh ƁL, Hankovszky P, Fodor GH, Tolnai J, SĆ¼dy R, KovĆ”cs BN, MolnĆ”r A, Babik B. Dopamine reverses lung function deterioration after cardiopulmonary bypass without affecting gas exchange. J Cardiothorac Vasc Anesth. 2022;36(4):1047ā€“55.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  12. Crocetti L, Giovannoni MP, Cantini N, Guerrini G, Vergelli C, Schepetkin IA, Khlebnikov AI, Quinn MT. Novel sulfonamide analogs of sivelestat as potent human neutrophil elastase inhibitors. Front Chem. 2020;8:795.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  13. Aikawa N, Ishizaka A, Hirasawa H, Shimazaki S, Yamamoto Y, Sugimoto H, Shinozaki M, Taenaka N, Endo S, Ikeda T, et al. Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study. Pulm Pharmacol Ther. 2011;24(5):549ā€“54.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  14. Kumagai K, Saikawa Y, Takeuchi H, Suda K, Fukuda K, Nakamura R, Takahashi T, Kawakubo H, Wada N, Miyasho T, et al. The neutrophil elastase inhibitor sivelestat suppresses accelerated gastrointestinal tumor growth via peritonitis after cecal ligation and puncture. Anticancer Res. 2013;33(9):3653ā€“9.

    CASĀ  PubMedĀ  Google ScholarĀ 

  15. Pu S, Wang D, Liu D, Zhao Y, Qi D, He J, Zhou G. Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. BMC Pulm Med. 2017;17(1):148.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  16. Ryugo M, Sawa Y, Takano H, Matsumiya G, Iwai S, Ono M, Hata H, Yamauchi T, Nishimura M, Fujino Y, et al. Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: findings of a double-blind randomized study. Surg Today. 2006;36(4):321ā€“6.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  17. Hagiwara S, Iwasaka H, Hidaka S, Hasegawa A, Noguchi T. Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Research: Official J Eur Histamine Res Soc [et al]. 2009;58(4):198ā€“203.

    ArticleĀ  CASĀ  Google ScholarĀ 

  18. Pan T, Tuoerxun T, Chen X, Yang CJ, Jiang CY, Zhu YF, Li ZS, Jiang XY, Zhang HT, Zhang H, et al. The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass. Front Immunol. 2023;14:1082830.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  19. Kurabayashi M, Okishige K, Azegami K, Ueshima D, Sugiyama K, Shimura T, Maeda M, Aoyagi H, Isobe M. Reduction of the PaO2/FiO2 ratio in acute aortic dissectionā€“ relationship between the extent of dissection and inflammationā€“. Circ J. 2010;74(10):2066ā€“73.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  20. Xing Z, Han J, Hao X, Wang J, Jiang C, Hao Y, Wang H, Wu X, Shen L, Dong X, et al. Immature monocytes contribute to cardiopulmonary bypass-induced acute lung injury by generating inflammatory descendants. Thorax. 2017;72(3):245ā€“55.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  21. Duan XZ, Xu ZY, Lu FL, Han L, Tang YF, Tang H, Liu Y. Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection. J Thorac Dis. 2018;10(3):1628ā€“34.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  22. Ji Q, Lai H, Sun Y, Luo Z, Liu L, Liu C, Gu J, Wang Y, Ding W, Wang C. Impact of presurgical mild acute respiratory distress syndrome on surgical mortality after surgical repair of acute type A aortic dissection. Int Heart J. 2017;58(5):739ā€“45.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  23. Ding Q, Wang Y, Yang C, Tuerxun D, Yu X. Effect of sivelestat in the treatment of acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Intensive Care Res. 2023:1ā€“10. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s44231-023-00032-9

  24. Nomura N, Asano M, Saito T, Nakayama T, Mishima A. Sivelestat attenuates lung injury in surgery for congenital heart disease with pulmonary hypertension. Ann Thorac Surg. 2013;96(6):2184ā€“91.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  25. Zhou Y, Li X, Chen H, Zhong X, Ren H. Efficacy and safety of sivelestat sodium for the treatment of inflammatory response in acute Stanford type A aortic dissection: a retrospective cohort study. J Thorac Dis. 2022;14(10):3975ā€“82.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  26. Dekker NAM, van Leeuwen ALI, van de Ven PM, de Vries R, Hordijk PL, Boer C, van den Brom CE. Pharmacological interventions to reduce edema following cardiopulmonary bypass: a systematic review and meta-analysis. J Crit Care. 2020;56:63ā€“72.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  27. Tang YX, Fan ZW, Li J, Pan HD, Su WX, Matniyaz Y, Zhang HT, Luo YX, Lv ZK, Wang WZ, Gao YX, Pan T, Xu WZ, Wang DJ. Sivelestat in patients at a high risk of postoperative acute lung injury after scheduled cardiac surgery: a prospective cohort study. J Inflamm Res. 2024;17:591ā€“601.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  28. Hagio T, Kishikawa K, Kawabata K, Tasaka S, Hashimoto S, Hasegawa N, Ishizaka A. Inhibition of neutrophil elastase reduces lung injury and bacterial count in hamsters. Pulm Pharmacol Ther. 2008;21(6):884ā€“91.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (82370273, 82241204, 82070420, and 82070503), the Development Program of Shanxi Province (2019ZDLSF01-01-02, 2021XC032, and 2022ZDLSF02-01), and the Research Program of Xijing Hospital (XJZT23XG28).

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Author notes

  1. Zhiyan Mai, Xudong Liu and Weixun Duan contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xiā€™an, 710032, China

    Zhiyan Mai,Ā Weixun Duan,Ā Chen Yang,Ā Yenong Zhou,Ā Tao Chen,Ā Jincheng LiuĀ &Ā Zhenxiao Jin

  2. Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, China

    Zhiyan MaiĀ &Ā Xudong Liu

  3. Department of Clinical Laboratory, Tangdu Hospital, Fourth Milittary Medical University, Xiā€™an, 710032, China

    Zheng Su

  4. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xiā€™an, 710069, China

    Yang Yang

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  10. Zhenxiao Jin
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Contributions

ZJ, WD, JL, YYand YW designed the clinical study. ZM, CY, and YZ collected clinical data and specimens. TC, CY, and ZS analyzed the data. ZJ, WD, CY, and YW wrote the article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhenxiao Jin.

Ethics declarations

Ethics approval and consent to participate

This was a single-center retrospective cohort study. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethical Committee of Xijing Hospital (KY20242093-C-1). The requirement for written consent was waived owing to its retrospective nature.

Competing interests

The authors declare no competing interests.

Clinical trial number

Not applicable.

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Mai, Z., Liu, X., Duan, W. et al. Efficacy of sivelestat in alleviating postoperative pulmonary injury in patients with acute aortic dissection undergoing total arch replacement: a retrospective cohort study. BMC Cardiovasc Disord 25, 121 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12872-025-04527-9

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12872-025-04527-9

Keywords

BMC Cardiovascular Disorders

ISSN: 1471-2261

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