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长期持续输注特利加压素可改善失代偿期肝硬化患者的心脏储备功能。

Long-Term Continuous Terlipressin Infusion Improves Cardiac Reserve in Patients With Decompensated Cirrhosis.

作者信息

Terbah Ryma, Koshy Anoop N, Majumdar Avik, Vaz Karl, Testro Adam, Sinclair Marie

机构信息

Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia.

Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia; Department of Cardiology, Austin Health, Heidelberg, Australia.

出版信息

Clin Gastroenterol Hepatol. 2024 Aug 30. doi: 10.1016/j.cgh.2024.08.010.

Abstract

BACKGROUND AND AIMS

Cardiac dysfunction is a key factor in the pathogenesis of hepatorenal syndrome, for which terlipressin is the recommended first-line treatment. This study investigates whether long-term terlipressin can ameliorate the subclinical cardiac dysfunction observed in decompensated cirrhosis.

METHODS

Twenty-two patients with decompensated cirrhosis and ascites enrolled in a prospective study of home continuous terlipressin infusion were included. Cardiac function was assessed using dobutamine stress echocardiogram before and after 12 weeks of terlipressin. The primary outcome was the impact of terlipressin on cardiac reserve, the change in cardiac output (CO) in response to stress.

RESULTS

The median age was 61 years (interquartile range, 56-64 years), the median Model for End-Stage Liver Disease score was 15 (interquartile range, 12.3-17.0), and 72.7% were male. The increase in CO in response to low-dose dobutamine was significantly higher following terlipressin (↑4.0 L/min [↑57.8%]) as compared with baseline (↑1.8 L/min [21.3%]) (P = .0001). The proportion of patients with impaired cardiac reserve (defined by ΔCO <25% after low-dose dobutamine) reduced from 81.8% at baseline to 40.9% after terlipressin, (P = .02), driven primarily by improvement in inotropic function. Resting CO decreased significantly after terlipressin from 8.9 ± 2.2 L/min to 7.2 ± 1.8 L/min (normal range 5-6 L/min) (P < .001), due to a decrease in stroke volume from 108 to 86 mL/beat (P = .006).

CONCLUSIONS

Long-term continuous terlipressin infusion resulted in a significant increase in cardiac reserve and attenuation of the hyperdynamic state usually observed in decompensated cirrhosis. These data provide important mechanistic insight into the pathogenesis and reversibility of cardiac dysfunction in cirrhosis. Future studies are required to evaluate whether long-term terlipressin can prevent hepatic decompensating events such as hepatorenal syndrome in high-risk individuals. Australian New Zealand Clinical Trials Registry, Number: ACTRN12619000891123.

摘要

背景与目的

心脏功能障碍是肝肾综合征发病机制中的关键因素,特利加压素是推荐的一线治疗药物。本研究旨在探讨长期使用特利加压素是否能改善失代偿期肝硬化患者中观察到的亚临床心脏功能障碍。

方法

纳入22例失代偿期肝硬化腹水患者,进行一项家庭持续输注特利加压素的前瞻性研究。在特利加压素治疗12周前后,采用多巴酚丁胺负荷超声心动图评估心脏功能。主要结局是特利加压素对心脏储备的影响,即应激状态下心输出量(CO)的变化。

结果

中位年龄为61岁(四分位间距,56 - 64岁),终末期肝病模型评分中位数为15(四分位间距,12.3 - 17.0),男性占72.7%。与基线相比,特利加压素治疗后低剂量多巴酚丁胺刺激引起的CO增加显著更高(↑4.0 L/min [↑57.8%]),而基线时为↑1.8 L/min [21.3%])(P = .0001)。心脏储备受损(定义为低剂量多巴酚丁胺刺激后ΔCO <25%)的患者比例从基线时的81.8%降至特利加压素治疗后的40.9%,(P = .02),主要是由于心肌收缩功能改善。特利加压素治疗后静息CO从8.9 ± 2.2 L/min显著降至7.2 ± 1.8 L/min(正常范围5 - 6 L/min)(P < .001),原因是每搏输出量从108 mL/次降至86 mL/次(P = .006)。

结论

长期持续输注特利加压素可显著增加心脏储备,并减轻失代偿期肝硬化患者通常观察到的高动力状态。这些数据为肝硬化心脏功能障碍的发病机制和可逆性提供了重要的机制性见解。未来需要开展研究,以评估长期使用特利加压素是否能预防高危个体发生肝肾综合征等肝脏失代偿事件。澳大利亚新西兰临床试验注册中心,注册号:ACTRN12619000891123。

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