Groszmann R J, Bosch J, Grace N D, Conn H O, Garcia-Tsao G, Navasa M, Alberts J, Rodes J, Fischer R, Bermann M
Veterans Administration Medical Center, West Haven, Connecticut.
Gastroenterology. 1990 Nov;99(5):1401-7. doi: 10.1016/0016-5085(90)91168-6.
In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.
在一项双盲随机试验中，对51例服用普萘洛尔的肝硬化食管静脉曲张患者和51例服用安慰剂的患者的血流动力学事件进行了前瞻性研究。在治疗开始时的基线以及治疗开始后的3个月、12个月和24个月测定肝静脉压力梯度、心率和静脉曲张大小。两组的基线值相似。3个月时，普萘洛尔治疗组的肝静脉压力梯度显著降低（从18.1±4.2降至15.7±3.4 mmHg；P<0.05），而接受安慰剂治疗的患者则未降低（从19.6±6.8降至17.5±5.3 mmHg；无显著性差异）。在随后的时间间隔内，两组的该梯度均从基线值显著降低。普萘洛尔治疗组的心率在所有时间均显著降低（P<0.001）。13例患者发生静脉曲张出血（11例服用安慰剂，2例服用普萘洛尔；P<0.01），所有这些患者的肝静脉压力梯度均大于12 mmHg。21例患者（14例服用普萘洛尔，7例服用安慰剂）的肝静脉压力梯度降至小于或等于12 mmHg；他们均未发生食管静脉曲张出血，死亡率也有所降低。由于大多数出血事件发生在第一年（10例服用安慰剂，1例服用普萘洛尔；P<0.01），普萘洛尔似乎在肝静脉压力梯度下降最大的时期具有保护作用。由于将肝静脉压力梯度降至小于12 mmHg可预防静脉曲张出血并提高生存率，这应是门静脉高压症药物治疗的目标。
