Kaluski Edo, Kobrin Isaac, Zimlichman Reuven, Marmor Alon, Krakov Oscar, Milo Olga, Frey Aline, Kaplan Shoshana, Krakover Rikardo, Caspi Avi, Vered Zvi, Cotter Gad
Cardiology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.
J Am Coll Cardiol. 2003 Jan 15;41(2):204-10. doi: 10.1016/s0735-1097(02)02708-0.
The objective of this study was to evaluate the addition of intravenous (IV) tezosentan to standard therapy for patients with pulmonary edema.
Tezosentan is an IV nonselective endothelin (ET)-1 antagonist that yields favorable hemodynamic effects in patients with acute congestive heart failure (CHF).
Pulmonary edema was defined as acute CHF leading to respiratory failure, as evidenced by an oxygen saturation (SO(2)) <90% by pulse oxymeter despite oxygen treatment. All patients received oxygen 8 l/min through a face mask, 3 mg of IV morphine, 80 mg of furosemide, and 1 to 3 mg/h continuous drip isosorbide-dinitrate according to their blood pressure level and were randomized to receive a placebo or tezosentan (50 or 100 mg/h) for up to 24 h.
Eighty-four patients were randomized. The primary end point, the change in SO(2) from baseline to 1 h, was 9.1 +/- 6.3% in the placebo arm versus 7.6 +/- 10% in the tezosentan group (p = NS). The incidence of death, recurrent pulmonary edema, mechanical ventilation, and myocardial infarction during the first 24 h of treatment was 19% in both groups. Reduced baseline SO(2), lower echocardiographic ejection fraction, high baseline mean arterial blood pressure (MAP), and inappropriate vasodilation (MAP reduction at 30 min of <5% or >30%) correlated with worse outcomes. A post-hoc analysis revealed that the outcome of patients who received only 50 mg/h tezosentan was better than patients in the placebo group whereas patients receiving 100 mg/h had the worst outcomes.
In the present study, tezosentan (an ET-1 antagonist) did not affect the outcome of pulmonary edema, possibly because of the high dose used.
本研究旨在评估在肺水肿患者的标准治疗中加用静脉注射替唑生坦的效果。
替唑生坦是一种静脉注射用非选择性内皮素（ET）-1拮抗剂，对急性充血性心力衰竭（CHF）患者具有良好的血流动力学效应。
肺水肿定义为急性CHF导致呼吸衰竭，尽管进行了氧疗，但经脉搏血氧仪测定氧饱和度（SO₂）<90%可作为证据。所有患者通过面罩接受8升/分钟的氧气、3毫克静脉注射吗啡、80毫克呋塞米，并根据血压水平接受1至3毫克/小时的硝酸异山梨酯持续静脉滴注，然后随机接受安慰剂或替唑生坦（50或100毫克/小时）治疗长达24小时。
84例患者被随机分组。主要终点指标，即从基线到1小时SO₂的变化，安慰剂组为9.1±6.3%，替唑生坦组为7.6±10%（p=无显著性差异）。两组在治疗的前24小时内死亡、复发性肺水肿、机械通气和心肌梗死的发生率均为19%。基线SO₂降低、超声心动图射血分数较低、基线平均动脉血压（MAP）较高以及不适当的血管舒张（30分钟时MAP降低<5%或>30%）与较差的预后相关。事后分析显示，仅接受50毫克/小时替唑生坦治疗的患者的预后优于安慰剂组患者，而接受100毫克/小时治疗的患者预后最差。
在本研究中，替唑生坦（一种ET-1拮抗剂）未影响肺水肿的预后，可能是因为使用的剂量较高。
