Burroughs A K, McCormick P A
Hepato-biliary and Liver Transplantation Unit, Royal Free Hospital, Hampstead, London, United Kingdom.
Surg Clin North Am. 1990 Apr;70(2):319-39. doi: 10.1016/s0039-6109(16)45084-x.
Beta-blockers modify splanchnic hemodynamics in cirrhotic patients. Nonselective beta-blockers are more effective than selective beta-blockers. Azygos blood flow, as a measure of collateral circulation, including that through varices, is always reduced, but the effects on portal pressure, whether measured directly or by the wedged hepatic venous pressure, are variable. The initial reported correlation between a 25% reduction of resting pulse rate and similar percentage reduction in the wedged free hepatic venous gradient has not been reproduced in subsequent studies. Therefore, to study the effect of changes in hemodynamic indices and the likelihood of variceal bleeding, direct measurements of such indices need to be made in clinical trials. At present, only one primary-prevention trial of propranolol suggests that a hemodynamic index can be used to identify patients given propranolol who will not bleed. Some clinical factors may be important in identifying nonresponders in trials of secondary prevention, but these are not universally recognized. The results of secondary-prevention studies are very heterogeneous, and it is difficult to understand why this is so. However, comparative studies versus sclerotherapy suggest that reductions in rebleeding and mortality are similar. Pharmacologic treatment, including beta-blockade, is ideal for primary prevention of variceal bleeding. The initial results from randomized studies are more homogeneous regarding the benefit of beta-blockers than in the secondary-prevention studies, although there is still doubt about the response in cirrhotics with ascites. No fatal complications due to propranolol administration have been reported in cirrhotic patients, and the complications are reversible. The future of pharmacologic therapy for portal hypertension lies in combination therapy. The addition of vasodilators to beta-blockers appears to potentiate their effect on portal pressure reduction. The results of clinical trials are awaited with great interest.
β受体阻滞剂可改变肝硬化患者的内脏血流动力学。非选择性β受体阻滞剂比选择性β受体阻滞剂更有效。奇静脉血流量作为侧支循环的一种测量指标，包括通过静脉曲张的血流量，总是会减少，但对门静脉压力的影响，无论是直接测量还是通过肝静脉楔压测量，都是可变的。最初报道的静息心率降低25%与肝静脉楔压自由梯度降低相似百分比之间的相关性在后续研究中并未得到重现。因此，为了研究血流动力学指标变化的影响以及静脉曲张出血的可能性，需要在临床试验中直接测量这些指标。目前，只有一项普萘洛尔的一级预防试验表明，血流动力学指标可用于识别服用普萘洛尔后不会出血的患者。在二级预防试验中，一些临床因素可能对识别无反应者很重要，但这些因素尚未得到普遍认可。二级预防研究的结果非常不一致，很难理解为何如此。然而，与硬化疗法的比较研究表明，再出血和死亡率的降低相似。包括β受体阻滞剂在内的药物治疗是预防静脉曲张出血的理想方法。随机研究的初步结果显示，β受体阻滞剂的益处比二级预防研究中的结果更具同质性，尽管对于腹水型肝硬化患者的反应仍存在疑问。在肝硬化患者中，尚未有因服用普萘洛尔而导致致命并发症的报道，且这些并发症是可逆的。门静脉高压药物治疗的未来在于联合治疗。在β受体阻滞剂中添加血管扩张剂似乎可增强其降低门静脉压力的效果。人们对临床试验的结果拭目以待。
