乙酰半胱氨酸在急性呼吸窘迫综合征治疗中的作用

Role of N⁃acetylcysteine in the treatment of acute respiratory distress syndrome

摘要

目的：分析乙酰半胱氨酸（NAC）在治疗急性呼吸窘迫综合征（ARDS）患者中的作用。方法：采用单中心回顾性队列研究，选取2020年1月至2024年12月在武汉大学人民医院重症医学科住院的ARDS患者65例，其中39名使用了NAC治疗（NAC组），26名未使用（对照组）。比较两组患者在一般资料、重病监护病房（ICU）住院时间（采用同一病情下ICU累计住院时间，修正医保结算导致的非医疗性中转偏倚）、总住院时间、机械通气时间、连续肾脏替代治疗（CRRT）时间、凝血功能、血常规、降钙素原、肝肾功能及血气结果上的差异，运用卡方检验、独立样本t检验、Mann⁃Whitney U检验、配对样本t检验等统计学方法，以P<0.05认为差异有统计学意义。结果：两组患者年龄有差异（P=0.003），其余基线资料、ICU住院时间、总住院时间、机械通气时间、CRRT时间无明显差异（P>0.05）。与对照组相比，NAC组患者治疗后的乳酸水平显著降低（P=0.030）。与基线相比，NAC组患者治疗后的凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）均延长（均P<0.05），动脉二氧化碳分压升高（P=0.001）；对照组患者治疗后的APTT缩短（P=0.017），乳酸明显增加（P=0.037）。两组患者治疗后的红细胞、血红蛋白、血小板均较基线水平显著下降（均P<0.05）。结论：乙酰半胱氨酸的使用可以显著降低ARDS患者动脉血中的乳酸水平，改善组织灌注和氧合状态。

Abstract

Objective: To analyze the therapeutic efficacy of N⁃acetylcysteine (NAC) in the treatment of acute respiratory distress syndrome (ARDS) through a retrospective study. Methods: A single⁃center retrospective cohort study consisted of 65 ARDS patients in the Department of Critical Care Medicine at Renmin Hospital of Wuhan University from January 2020 to December 2024, including 39 patients who received NAC treatment (NAC group) and 26 did not (control group). Differences in general conditions, ICU length of stay (using cumulative ICU length of stay for the same episode of illness to correct bias from non⁃medical transfers attributable to medical insurance settlement policies), total length of hospital stay, mechanical ventilation time, continuous renal replacement therapy (CRRT) time as well as coagulation function, blood routine, inflammatory marker procalcitonin, liver function, renal function, and blood gas results between the two groups were compared by the Chi⁃square test, independent samples t⁃test, Mann⁃Whitney U test, and paired samples t⁃test. Results: Except for age (P=0.003), there was no significant difference in the other baseline indicators, ICU length of stay, total hospitalization time, mechanical ventilation time and CRRT time between the two groups (P>0.05). Relative to the control group, the NAC group exhibited a marked post⁃treatment reduction in lactic acid (Lac) levels (P=0.030). Compared with baseline, patients in the NAC group exhibited prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) (all P<0.05), along with elevated partial pressure of arterial carbon dioxide (P=0.001) following medication administration; whereas control group patients had shortened APTT (P=0.017) and significantly increased Lac levels after treatment (P=0.037). After medication, red blood cell, hemoglobin, and platelet levels in both groups decreased significantly compared to the baseline levels (all P<0.05). Conclusion: The administration of NAC can substantially lower arterial lactate levels and improve tissue perfusion and oxygenation status.

关键词

急性呼吸窘迫综合征 / 乙酰半胱氨酸 / 临床疗效 / 乳酸 / 凝血功能

Key words

Acute Respiratory Distress Syndrome / N⁃Acetylcysteine / Therapeutic Efficacy / Lactic Acid / Coagulation Function

参考文献

[1] MATTHAY M A, ARABI Y, ARROLIGA A C, et al. A new global definition of acute respiratory distress syndrome [J]. Am J Respir Crit Care Med, 2024, 209(1): 37-47.

[2] BELLANI G, LAFFEY J G, PHAM T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries [J]. JAMA, 2016, 315(8): 788-800.

[3] BEITLER J R, THOMPSON B T, BARON R M, et al. Advancing precision medicine for acute respiratory distress syndrome [J]. Lancet Respir Med, 2022, 10(1): 107-120.

[4] THOMPSON B T, CHAMBERS R C, LIU K D. Acute respiratory distress syndrome [J]. N Engl J Med, 2017, 377(6): 562-572.

[5] YANG S C, TSAI Y F, PAN Y L, et al. Understanding the role of neutrophils in acute respiratory distress syndrome [J]. Biomed J, 2021, 44(4): 439-446.

[6] JOFFRE J, HELLMAN J, INCE C, et al. Endothelial responses in sepsis [J]. Am J Respir Crit Care Med, 2020, 202(3): 361-370.

[7] BOS L D J, WARE L B. Acute respiratory distress syndrome: Causes, pathophysiology, and phenotypes [J]. Lancet, 2022, 400(10358): 1145-1156.

[8] RAGHU G, BERK M, CAMPOCHIARO P A, et al. The multifaceted therapeutic role of N—Acetylcysteine (NAC) in disorders characterized by oxidative stress [J]. Curr Neuropharmacol, 2021, 19(8): 1202-1224.

[9] MEYER N J, GATTINONI L, CALFEE C S. Acute respiratory distress syndrome [J]. Lancet, 2021, 398(10300): 622-637.

[10] LIAU L L, RUSZYMAH B H I, NG M H, et al. Characteristics and clinical applications of Wharton's jelly—derived mesenchymal stromal cells [J]. Curr Res Transl Med, 2020, 68(1): 5-16.

[11] MOKRA D, PORVAZNIK I, MOKRY J. N—Acetylcysteine in the treatment of acute lung injury: Perspectives and limitations [J]. Int J Mol Sci, 2025, 26(6): 2657.

[12] JOFFRE J, HELLMAN J. Oxidative stress and endothelial dysfunction in sepsis and acute inflammation [J]. Antioxid Redox Signal, 2021, 35(15): 1291-1307.

[13] ISPOR. Cost—effectiveness analysis of the use of N—acetyl cysteine as part of the treatment to ARDS on the COVID—19 scenario[C].International Society for Pharmacoeconomics and Outcomes Research Annual Meeting, 2022.

[14] SCHLOSS J, LEACH M, BROWN D, et al. The effects of N—acetyl cysteine on acute viral respiratory infections in humans: A rapid review [J]. Adv Integr Med, 2020, 7(4): 232-239.

基金资助

新发突发与重大传染病防控国家科技重大专项(2025ZD01902600)

武汉大学人民医院交叉创新人才项目(JCRCYG⁃2022⁃005)

广东省二十一世纪教育基金会项目(2023HX0074)