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Effect of ulinastatin on interleukins and pulmonary function in bypass patients: a meta-analysis of randomized controlled trials

Wirkung von Ulinastatin auf Interleukine und die Lungenfunktion von Bypasspatienten: Eine Metaanalyse randomisierter kontrollierter Studien

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Abstract

Background

Our aim was to evaluate the effect of urinary trypsin inhibitors (UTI) on interleukin, tumor necrosis factor-α (TNF-α), and polymorphonuclear neutrophil elastase (PMNE) levels as well as on pulmonary function in patients undergoing cardiopulmonary bypass.

Materials and methods

We searched the following databases for relevant studies: PubMed, Medline (Ovid SP), Cochrane Library, Wanfang Data, China Biology Medicine Database, Chinese Periodical Database, China Knowledge Resource Integrated Database, and Chinese Clinical Trial Registry. Two investigators independently collected the data and assessed the quality of each study. RevMan 5.3 was used for the meta-analysis.

Results

In total, 15 randomized controlled trials (646 patients) met the inclusion criteria. There was a significant decrease in TNF-α, interleukin-6 (IL-6), IL-8, and PMNE levels at 6 h and 24 h after UTI treatment and an increase in IL-10 levels; additionally, there was a decrease in respiratory index and an improvement in the oxygenation index. Nevertheless, UTI treatment did not affect the length of intensive care unit stay, alveolar–arterial oxygen partial pressure difference, adverse lung events, or hospital mortality. Because of the high heterogeneity of the included trials, the results should be assessed carefully.

Conclusion

UTI treatment can suppress proinflammatory cytokine elevation and upregulate the release of anti-inflammatory mediators, thereby reducing pulmonary injury and improving pulmonary function after cardiopulmonary bypass.

Zusammenfassung

Hintergrund

Ziel der vorliegenden Studie war die Beurteilung der Wirkung des Urin-Trypsininhibitors (UTI) auf die Werte für Interleukin, Tumornekrosefaktor-α (TNF-α) und Elastase aus polymorphkernigen Neutrophilen („polymorphonuclear neutrophil elastase“, PMNE) sowie auf die Lungenfunktion von Patienten, bei denen eine kardiopulmonale Bypassoperation erfolgte.

Material und Methoden

Folgende Datenbanken wurden nach relevanten Studien durchsucht: PubMed, Medline (Ovid SP), Cochrane Library, Wanfang Database, China Biology Medicine Database, Chinese Periodical Database, China Knowledge Resource Integrated Database und Chinese Clinical Trial Registry. Unabhängig voneinander sammelten 2 Untersucher die Daten und bewerteten die Qualität jeder Studie. Die Software RevMan 5.3 wurde für die Metaanalyse eingesetzt.

Ergebnisse

Insgesamt erfüllten 15 randomisierte kontrollierte Studien (646 Patienten) die Einschlusskriterien. Es fanden sich eine signifikante Abnahme der Werte von TNF-α, Interleukin-6 (IL-6), IL-8 und PMNE 6 h und 24 h nach UTI-Therapie und ein Anstieg der IL-10-Werte; zusätzlich bestand eine Verminderung des respiratorischen Index und eine Verbesserung des Oxygenierungsindex. Trotzdem wirkte sich die UTI-Therapie nicht auf die Länge des Aufenthalts auf der Intensivstation, die alveoloarterielle Sauerstoffpartialdruckdifferenz, unerwünschte Lungenereignisse oder die Krankenhausmortalität aus. Wegen der großen Heterogenität der eingeschlossenen Studien sollten die Ergebnisse sorgfältig geprüft werden.

Schlussfolgerung

Durch eine UTI-Therapie kann die Erhöhung proinflammatorischer Zytokinwerte unterbunden und die Freisetzung antiinflammatorischer Mediatoren heraufreguliert werden, dies kann zur Verminderung von Lungenschädigungen sowie zur Verbesserung der Lungenfunktion nach kardiopulmonalem Bypass führen.

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Funding

This work was supported by the Health and Family Planning Commission Foundation of Hubei province, China (Grant No. WJ2015MB260) and Research Fund for Excellent Dissertation of China Three Gorges University (Grant No. 2018SSPY094).

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Authors and Affiliations

  1. Department of Respiratory Medicine, The First College of Clinical Medical Sciences, Yichang Central People’s Hospital, China Three Gorges University, Yiling Road 183, 443000, Yichang, Hubei, China

    G. He, W. Li, Y. Ruan, X. Xiong, X. Song & F. Zeng

  2. Department of Cardiology, The First College of Clinical Medical Sciences, Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, Hubei, China

    Q. Li

  3. Institute of Evidence-Based and Translational Medicine, China Three Gorges University, Yichang, Hubei, China

    G. He, Q. Li, W. Li, Y. Ruan, X. Xiong, X. Song & F. Zeng

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Correspondence to F. Zeng.

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Conflict of interest

G. He, Q. Li, W. Li, Y. Ruan, X. Xiong, X. Song, and F. Zeng declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

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Authors’ contributions

Guiyuan He and Qi Li contributed equally to this paper. The identification of titles and abstracts and extracting of data were independently carried out by Guiyuan He and Qi Li. Wenxin Li and Yushu Ruan were responsible for resolving potential disagreement between Guiyuan He and Qi Li. Xiaoqi Xiong and Xinyu Song performed the literature review. All authors contributed to the writing of the draft and approved the final manuscript. The corresponding author, Fanjun Zeng, contributed to the development of the protocol and prepared the manuscript.

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He, G., Li, Q., Li, W. et al. Effect of ulinastatin on interleukins and pulmonary function in bypass patients: a meta-analysis of randomized controlled trials. Herz 45, 335–346 (2020). https://doi.org/10.1007/s00059-018-4732-0

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