Ludwig D, Schädel S, Brüning A, Schiefer B, Stange E F
Department of Internal Medicine I, University of Lübeck, Germany.
Dig Dis Sci. 2000 May;45(5):1019-27. doi: 10.1023/a:1005553914878.
Octreotide is effective during 48 h in the treatment of acute variceal bleeding, probably by reducing variceal blood flow and pressure. Its basal and postprandial effects on splanchnic and systemic hemodynamics, and hormonal changes over this time interval have not yet been studied. Twenty-four patients with cirrhosis and portal hypertension were randomized to receive a liquid meal and either octreotide (Oct, 100 microg bolus intravenous, followed after 2 h by a continuous infusion of 25 microg/hr for 20 hr) or placebo (Plac) given at three consecutive days. Splanchnic (Doppler ultrasound) and systemic hemodynamics (noninvasive cardiac monitoring) were assessed on four consecutive days (one control day and three treatment days) during 2 hr. The postprandial increase in mean blood velocity of the superior mesenteric artery (SMA-V(mean) +44%), portal blood velocity (PV-V(mean), +44%) and total hepatic blood flow (HBF, +40%) observed in the placebo group during the control day was abolished during the first day of treatment (SMA-V(mean), +3%, P < 0.01; PV-V(mean), +6%, P < 0.05; HBF, -25%, P < 0.01) and still reduced after 48 hr in the octreotide group (SMA-V(mean) +28%, P < 0.05; PV-V(mean), +22%, P > 0.05; HBF, -8%, P < 0.05). The postprandial increase in cardiac index (CI, + 10%) and decrease in systemic vascular resistance index (SVRI, -6%) were blunted after the initial injection of octreotide only (CI, -8%, P < 0.05; SVRI, +18%, P < 0.01). Endothelin-1-levels, which were increased at baseline (Plac 25 +/- 17, Oct 16 +/- 13 ng/liter, P > 0.05) decreased significantly after 48 hr of treatment with octreotide (Plac 27 +/- 20, Oct 8 +/- 4 ng/liter, P < 0.05). Octreotide is effective during 48 hr in the prevention of postprandial hyperemia in cirrhotics, even if its efficacy is decreasing over time. Moreover it may have positive effects on systemic vasodilation in cirrhotics. These findings suggest a potential role of this drug in the chronic treatment of portal hypertension.
奥曲肽在治疗急性静脉曲张出血的48小时内有效，可能是通过减少曲张静脉的血流和压力。其对内脏和全身血流动力学的基础及餐后影响，以及在此时间段内的激素变化尚未得到研究。24例肝硬化和门静脉高压患者被随机分为两组，连续三天分别接受流食并给予奥曲肽（Oct，静脉推注100微克，2小时后以25微克/小时的速度持续输注20小时）或安慰剂（Plac）。在连续四天（一天对照日和三天治疗日）的2小时内评估内脏（多普勒超声）和全身血流动力学（无创心脏监测）。安慰剂组在对照日观察到的餐后肠系膜上动脉平均血流速度（SMA-V(mean) +44%）、门静脉血流速度（PV-V(mean)，+44%）和肝脏总血流量（HBF，+40%）的增加在治疗第一天被消除（SMA-V(mean)，+3%，P < 0.01；PV-V(mean)，+6%，P < 0.05；HBF，-25%，P < 0.01），奥曲肽组在48小时后仍降低（SMA-V(mean) +28%，P < 0.05；PV-V(mean)，+22%，P > 0.05；HBF，-8%，P < 0.05）。仅在最初注射奥曲肽后，餐后心脏指数（CI，+ 10%）的增加和全身血管阻力指数（SVRI，-6%）的降低受到抑制（CI，-8%，P < 0.05；SVRI，+18%，P < 0.01）。内皮素-1水平在基线时升高（Plac 25 +/- 17，Oct 16 +/- 13纳克/升，P > 0.05），在奥曲肽治疗48小时后显著降低（Plac 27 +/- 20，Oct 8 +/- 4纳克/升，P < 0.05）。奥曲肽在48小时内对预防肝硬化患者餐后充血有效，即使其疗效随时间降低。此外，它可能对肝硬化患者的全身血管舒张有积极作用。这些发现提示该药物在门静脉高压的慢性治疗中可能具有潜在作用。
