Short-term effects of propranolol on portal venous pressure

The present study was designed to investigate the effect of propranolol on portal pressure of patients with alcoholic cirrhosis and portal hypertension and to correlate these effects with clinical and laboratory parameters. The mean baseline hepatic venous pressure gradient in the 50 patients studied was of 18.2 +/- 4.1 mm Hg. It decreased significantly 2 hr after the oral administration of 40 mg of propranolol to 15.7 +/- 4.2 mm Hg (a mean reduction of 13.4 +/- 17%). This reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure. There was no correlation between the decrease in hepatic venous pressure gradient and the decrease in heart rate. When results were analyzed individually, only 15 (30%) showed a large decrease in hepatic venous pressure gradient (greater than 20%), 15 (30%) showed a moderate decrease (10 to 19%), and in 20 patients (40%) there was no reduction or an increase in hepatic venous pressure gradient. Comparison of "responders" (those that reduced hepatic venous pressure gradient greater than 10%) and "nonresponders" (hepatic venous pressure gradient reduction less than 10%) showed no significant differences in baseline laboratory and hemodynamic parameters, in the severity of the liver disease, in the heart rate and blood pressure response to propranolol, nor in the propranolol plasma levels achieved 2 hr after propranolol administration. Propranolol plasma levels correlated with the reduction in heart rate but not with the reduction in hepatic venous pressure gradient. Of 14 nonresponders to 40 mg of propranolol who received additional doses, six showed a reduction in hepatic venous pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Meta analysis of propranolol effects on gastrointestinal hemorrhage in cirrhotic patients

AIM: To assess the effects of propranolol as compared with placebo on gastrointestinal hemorrhage and total mortality in cirrhotic patients by using meta analysis of 20 published randomized clinical trials. METHODS: A meta analysis of published randomized clinical trials was designed. Published articles were selected for study based on a computerized MEDLINE and a manual search of the bibliographies of relevant articles. Data from 20 relevant studies fulfilling the inclusion criteria were retrieved by means of computerized and manual search. The reported data were extracted on the basis of the intention-to-treat principle, and treatment effects were measured as risk differences between propranolol and placebo. Pooled estimates were computed according to a random-effects model. We evaluated the pooled efficacy of propranolol on the risk of gastrointestinal hemorrhage and the total mortality. RESULTS: A total of 1,859 patients were included in 20 trials, 931 in the propranolol groups and 928 as controls. Among the 652 patients with upper gastrointestinal tract hemorrhage, 261 patients were treated with propranolol, and 396 patients were treated with placebo or non-treated. Pooled risk differences of gastrointestinal hemorrhage were -18 % [95 % CI, -25 %, -10 %] in all trials, -11 % [95 % CI, -21 %, -1 %] in primary prevention trials, and -25 % [95 % CI, -39 %, -10 %] in secondary prevention trials. A total of 440 patients died, 188 in propranolol groups and 252 in control groups. Pooled risk differences of total death were -7 % [95 % CI, -12 %, -3 %] in all trials, -9 % [95 % CI, -18 %, -1 %] in primary prevention trials, and -5 % [95 % CI, -9 %, -1 %] in secondary prevention trials. CONCLUSION: Propranolol can markedly reduce the risks of both primary and recurrent gastrointestinal hemorrhage, and also the total mortality.     

卡维地洛与普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度效果的对比分析

目的探讨卡维地洛和普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度(HVPG)的幅度、应答率以及用药后不良反应的差异,对卡维地洛降低门静脉压力的有效性和安全性进行评价。方法收集2010年10月-2012年1月在山东大学附属省立医院确诊的64名肝硬化门静脉高压患者,随机分为2组:普萘洛尔组(n=33)和卡维地洛组(n=31),根据血压和心率调整剂量,疗程7 d,均于治疗前后行HVPG测定及肝肾功能指标检测,比较2组患者HVPG降低的幅度及应答率,并观察患者低血压、腹水、肾损伤等不良反应的发生情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验或Fisher精确概率法。结果卡维地洛组和普萘洛尔组的HVPG均明显降低,降低幅度分别为(28.30±22.19)%和(12.38±24.09)%,其中卡维地洛组降低更明显,差异有统计学意义(t=0.223 4,P=0.032)。2组应答率分别为:卡维地洛组56.7%(17/30),普萘洛尔组41.9%(13/31),2组差异无统计学意义(χ2=1.324,P=0.250)。卡维地洛组平均动脉压的降低较普萘洛尔组明显,差异有统计学意义(t=2.338,P=0.024),但患者未出现明显低血压的不良反应;2组患者胆红素、血肌酐和尿素氮在治疗前后无明显升高,亦无腹水生成或加重的趋势。结论本研究提示在短期内卡维地洛降低HVPG的作用较普萘洛尔显著,且无明显不良反应;其用于肝硬化门静脉高压的治疗是安全有效的。     

Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients

AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient(HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.RESULTS: Subjects comprised patients with a median age of 65(range, 40-82) years. According to the ChildPugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were-1.0 kg(P = 2.04 × 10~(-6)) and-1.3 kg(P = 1.83 × 10~(-5)), respectively. The median HVPG value was 240(range, 105-580) mm H2 O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mm H_2 O in predicting treatment response. The response rate was 87.5%(7/8) in patients with HVPG of 190 mm H2 O or less, whereas it was only 12.5%(2/16) in those with HVPG of greater than 190 mm H2O(P = 7.46 × 10~(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG(P = 0.045) and serum hyaluronic acid(P = 0.017) were detected as useful factors.CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.     

Effects of long-term Irbesartan in reducing portal pressure in cirrhotic patients: comparison with propranolol in a randomised controlled study

BACKGROUND/AIMS: The role of angiotensin II (AT-II) type I receptor antagonists in the treatment of portal hypertension remains controversial. We tested the efficacy of Irbesartan (Irb) vs. Propranolol (Pro) in reducing portal pressure and evaluated its systemic haemodynamic effects. METHODS: Thirty-four patients were randomly assigned to receive either Irb 300 mg/day (19 patients) or Pro 40-120 mg/day (15 patients) for 2 months. RESULTS: Irb was discontinued in five patients (26%). No major side effect occurred in the Pro group. On an average, the portal pressure gradient decreased significantly more in the Pro than in the Irb group (median -19.5%, range -11/-31% vs. -4.8%, +2.5/-10%, P<0.001). A clinically significant decrease was seen in one (7%) of the patients given Irb vs. five (33%) given Pro (P<0.02). The fall in mean arterial pressure was significantly higher with Irb than with Pro (median -29%, range -15/-45% vs. -4.9%, +8/-19%, P<0.02). Irb significantly modified the blood creatinine clearance (median -29 ml/m, range +9/-61 ml/m, -30, -24/-35% P<0.0001 vs. basal). CONCLUSIONS: Irb offers no advantage over Pro in the control of portal hypertension. Moreover, its therapeutic profile is limited by important side effects.     

Effect of early propranolol administration on portal hypertensive gastropathy in cirrhotic rats

AIM： To investigate any protective effect of early propranolol administration in the development of portal hypertensive gastropathy in cirrhotic rats. METHODS： For the development of liver cirrhosis and portal hypertensive gastropathy, 60 rats underwent ligation of the left adrenal vein and complete devascularization of the left renal vein, followed by phenobarbital and carbon tetrachloride （CCl4） administration. After two weeks of CCl4 administration, the rats were randomly separated into two groups. In group A, propranolol was continuously administered intragastrically throughout the study, whereas in group B normal saline （placebo） was administered instead. Hemodynamic studies and vascular morphometric analysis of gastric sections were performed after complete induction of cirrhosis. RESULTS： Vascular morphometric studies showed higher numbers of vessels in all mucosal layers in the control group. Statistical analysis revealed a significantly higher total vascular surface in the control group compared to the propranolol group, but with no statistically significant difference between the mean vascular surfaces between the groups. Our study clearly shows that the increased mucosal blood flow is manifested by a marked increase of vessel count. CONCLUSION： Early propranolol＇s administration in portal hypertensive cirrhotic rats seems to prevent intense gastric vascular congestion that characterizes portal hypertensive gastropathy.     

Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients

Different and contradictory results concerning the use of propranolol in the treatment of portal hypertension have been reported. This study was designed to investigate the hemodynamic effects of short- and long-term administration of propranolol in portal hypertensive patients. Portal pressure, cardiac index, heart rate and blood pressure were obtained in 18 unselected alcoholic cirrhotic patients with esophageal varices before and 60 min after the oral administration of 40 mg propranolol and again after 106 +/- 35 days of continuous oral administration (mean dose = 158 +/- 63 mg per day). Baseline portal pressure was 21.7 +/- 7.2 mm Hg. It decreased after 60 min to 17.2 +/- 5.5 mm Hg (p less than 0.01) and after long-term administration of propranolol to 16.1 +/- 5.7 mm Hg (p less than 0.01). No decrease in portal pressure was noted in 9 of 18 (50%) patients after acute administration and 5 of 17 (30%) patients after long-term administration. Baseline cardiac index was 5.1 +/- 1.2 liters X min-1 X m-2. It decreased after 60 min to 3.9 +/- 1.4 liters X min-1 X m-2 (p less than 0.01) and to 3.6 +/- 1.0 liters X min-1 X m-2 after long-term administration (p less than 0.001). Baseline heart rate was 85 +/- 11 beats per min. It decreased after 60 min to 75 +/- 9 (p less than 0.001) and after long-term administration to 62 +/- 6 (p less than 0.001) beats per min. Baseline mean arterial pressure was 108 +/- 11 Hg. It decreased after 60 min to 97 +/- 14 mm Hg (p less than 0.01) and after long-term administration to 103 +/- 14 mm Hg (not statistically significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension

Abstract Nitroglycerin was administered orally to seven patients with cirrhosis and portal hypertension, to determine whether portal venous pressure (PVP) may be lowered without the systemic effects associated with its intravenous or sublingual use. PVP was measured via direct cannulation of the portal vein transhepatically using a Chiba needle. PVP decreased from 29 (s.d. = 4) to 22.7 (s.d. = 3.7) mmHg (22% mean fall) following 1.2 mg nitroglycerin with onset 7–15 min following ingestion, and the response persisted for up to 150 min. This was not associated with headache in any patient. Although a decrease in blood pressure was seen in most patients, this temporally followed the fall in PVP suggesting that it was a secondary response. Sublingual nitroglycerin was given to two patients without change in PVP yet both experienced severe headache. These findings support the hypothesis that oral nitroglycerin is delivered differentially to the portal venous bed with differential effects on PVP. Further studies are needed to evaluate this agent and this strategy for their potential role in long-term control of portal pressure.     

Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients

BACKGROUND/AIMS: Terlipressin decreases portal pressure. However, its effects on variceal pressure have been poorly investigated. This study investigated the variceal, splanchnic and systemic hemodynamic effects of terlipressin. METHODS: Twenty cirrhotic patients with esophageal varices grade II-III, and portal pressure > or =12 mmHg were studied. Hepatic venous pressure gradient, variceal pressure and systemic hemodynamic parameters were obtained. After baseline measurements, in a double-blind administration, 14 patients received a 2mg/iv injection of terlipressin and six patients received placebo. The same measurements were repeated 60 min later. RESULTS: No demographic or biochemical differences were observed in basal condition between groups. Terlipressin produced significant decreases in intravariceal pressure from 20.9+4.9 to 16.3+/-4.7 mmHg (p<0.01, -21+/- 16%), variceal pressure gradient from 18.9+/-4.8 to 13.5+/-6.0 mmHg (p<0.01, -28+/-27%), estimated variceal wall tension from 78+/-29 to 59+/-31 mmHg x mm (p<0.01, -27+/-22%), and hepatic venous pressure gradient from 19.4+/-4.5 to 16.8+/-5 mmHg (p<0.01, -14+/-12%) at 60 min. The change in variceal pressure after 60 min of terlipressin administration was greater than the change in wedge hepatic venous pressure (-4.7 mmHg vs -0.5 mmHg, respectively, p<0.0001). Terlipressin also caused significant decreases in heart rate and cardiac index and increases in mean arterial pressure and peripheral vascular resistance. CONCLUSIONS: Our results demonstrate that terlipressin produces significant and prolonged decreases in variceal pressure and variceal wall tension and has intrinsic effects on portal pressure and systemic hemodynamics. Variceal pressure provides a better assessment of the effects of terlipressin administration on esophageal varices than hepatic venous pressure gradient.     

肝硬化门静脉高压患者门静脉压力与FibroScan检测值相关性分析

目的探讨应用彩色多普勒超声显像仪以及瞬时弹性成像(Fibro Scan)观察和分析肝硬化患者门静脉压力与Fibro Scan之间的关系。方法选择2012年3月-2014年3月中山市第二人民医院收治的乙型肝炎肝硬化门静脉高压患者235例,另选健康人100例作为对照,使用彩色超声多普勒显像仪检测门静脉宽度(PVD)、门静脉平均血流速度(PVVmean)、门静脉血流量(PVQ),利用公式门静脉压力(Ppv)=1.895 1+0.001 1PVQ估算出Ppv。同时进行Fibro Scan检测。计量资料以均数±标准差(x±s)表示,组间比较采用t检验,各参数与Ppv关系采用双变量相关分析。结果肝硬化门静脉高压患者PVD、PVQ、Ppv和Fioro Scan值分别为(1.42±0.12)cm、(1238±145.23)ml/min、(3.28±0.17)k Pa和(27.81±7.52)k Pa,明显高于正常对照组(P值均0.05),Fibro Scan值和PVQ与肝硬化患者Ppv呈正相关,相关系数r分别为0.52、0.61,P值均0.001。结论 Fibro Scan测值可作为无创性评估肝硬化Ppv参考指标。     

Effects of propranolol on gastric mucosal perfusion and serum gastrin level in cirrhotic patients with portal hypertensive gastropathy

Gastric mucosal hyperemia associated with elevated serum gastrin level has been suggested in cirrhotic patients with portal hypertensive gastropathy (PHG). Clinical evidence has shown that these patients may benefit from propranolol administration. The aim of this study was to investigate effect of propranolol on gastric mucosal perfusion and serum gastrin level in cirrhotic patients with portal hypertensive gastropathy. Gastric mucosal perfusion was assessed by laser Doppler flowmetry. Measurements were performed under basal conditions and after observer-blind administration of propranolol (30–60 mg/day,N=9) or placebo (N=9) for seven days. Placebo had no effect on either gastric mucosal perfusion or serum gastrin level. In contrast, propranolol administration significantly decreased both antrum gastric mucosal perfusion (from 0.88±0.28 to 0.73±0.26 V,P<0.05) and corpus gastric mucosal perfusion (from 0.94±0.35 to 0.78±0.25 V,P<0.05). However, this drug had no effect on serum gastrin level. We conclude that chronic propranolol administration in cirrhotic patients with portal hypertensive gastropathy may reduce gastric mucosal perfusion without changing serum gastrin level.     

Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding

Background—Height of portalpressure correlates with severity of alcoholic cirrhosis. Portalpressure indices are not however used routinely as predictors of survival.
Aims—To examine the clinical valueof a single portal pressure measurement in predicting outcome incirrhotic patients who have bled.
Methods—A series of 105 cirrhoticpatients who consecutively underwent hepatic venous pressuremeasurement were investigated. The main cause of cirrhosis wasalcoholic (64.8%) and prior to admission all patients had bled from varices.
Results—During the follow up period(median 566 days, range 10-2555), 33 patients died, and 54 developedvariceal haemorrhage. Applying Cox regression analysis, hepatic venouspressure gradient, bilirubin, prothrombin time, ascites, and previouslong term endoscopic treatment were the only statistically independentpredictors of survival, irrespective of cirrhotic aetiology. Thepredictive value of the pressure gradient was much higher if themeasurement was taken within the first or the second week from thebleeding and there was no association after 15 days. A hepatic venouspressure gradient of at least 16 mm Hg appeared to identify patientswith a greatly increased risk of dying.
Conclusions—Indirectly measuredportal pressure is an independent predictor of survival in patientswith both alcoholic and non-alcoholic cirrhosis. In patients with aprevious variceal bleeding episode this predictive value seems to bebetter if the measurement is taken within the first two weeks from thebleeding episode. A greater use of this technique is recommended forthe prognostic assessment and management of patients with chronic liver disease.

Keywords:chronic liver disease; alcoholic cirrhosis; portalpressure

     

Relationship of portal pressure, anorectal varices and hemorrhoids in cirrhotic patients.

In a prospective study of 103 consecutive cirrhotic patients a high prevalence (43%) of anorectal varices was found compared with only 2% in 103 age- and sex-matched control subjects (p less than 0.001). However, there was no significant difference between the prevalences of hemorrhoids in cirrhotic patients and in control subjects (79% vs. 83%, p greater than 0.05). The hepatic venous pressure gradient of cirrhotic patients with anorectal varices was similar to cirrhotic patients without anorectal varices (14 +/- 6 mmHg, n = 22, vs. 16 +/- 7 mmHg, n = 39, p greater than 0.05. There was no significant difference in the hepatic venous pressure gradient between cirrhotic patients with and without hemorrhoids (15 +/- 6 mmHg, n = 47, vs. 16 +/- 8 mmHg, n = 14, p greater than 0.05). The prevalence of anorectal varices and hemorrhoids in cirrhotic patients had no relation to Child-Pugh's grading, esophageal varices with and without sclerotherapy and ascites. We conclude that anorectal varices are common in cirrhotic patients. Anorectal varices and hemorrhoids are not related to the degree of portal pressure.     

Double-blind investigation of the effects of propranolol and placebo on the pressure of esophageal varices in patients with portal hypertension

This study was aimed at investigating the effects of propranolol on esophageal variceal pressure in patients with portal hypertension. Variceal pressure was measured at endoscopy using a miniature pressure-sensitive gauge in 20 patients with portal hypertension. Measurements were obtained under baseline conditions and 20 min after double-blind administration of propranolol (0.15 mg/kg; n = 10) or an identical amount of placebo (normal saline, 0.3 ml/kg; n = 10). Under baseline conditions, variceal pressure was similar in propranolol and placebo groups (14.1 +/- 5 mm Hg vs. 14.9 +/- 6.6 mm Hg, respectively; not significant). Placebo had no significant effect on variceal pressure (baseline = 14.9 +/- 6.6 mm Hg; placebo = 15.5 +/- 6.6 mm Hg; not significant), and values after placebo administration were closely correlated with baseline values (r = 0.98; y = 1.1 + 0.97 x; p less than 0.0001). In contrast, propranolol caused a significant decrease in the pressure of esophageal varices (from 14.1 +/- 5 mm Hg to 11.3 +/- 4.4 mm Hg; p less than 0.0002). No significant changes in the size of esophageal varices were observed after propranolol or placebo administration. This study shows (a) the endoscopic pressure-gauge technique has a low variability and may be used to assess acute drug-induced changes in variceal pressure; and (b) propranolol causes significant decreases in variceal pressure in patients with portal hypertension and esophageal varices.     

经颈静脉肝内门体分流术对肝硬化门静脉高压症患者血流动力学的影响

[目的]观察经颈静脉肝内门体分流术(Transjugular intrahepatic portosystemic shunt,TIPS)对肝硬化门脉高压症患者门脉血流动力学的影响,探讨TIPS治疗肝硬化门脉高压症的有效性及机制。[方法]30例肝硬化门脉高压症患者,TIPS术前及术后,彩色多普勒超声测量门脉主干压、内径、血流速度及脾静脉内径。放射免疫法测定血浆肾素(PRA)、血管紧张素Ⅱ(ATⅡ)和血管内皮素(ET)浓度。[结果]30例患者术后的门脉压(24.8±3.6)cmH2O(1 cmH2O=0.098 kPa)与术前的(44.6±5.8)cmH2O比较;门脉内径(1.28±0.06)cm与术前的(1.65±0.09)cm比较;门脉血流速度(43.5±13.2)cm/s与术前的(11.6±3.8)cm/s比较;脾静脉内径(0.92±0.06)cm与术前的(1.24±0.04)cm比较,均P<0.01。血浆ET、PRA、ATⅡ浓度分别为(84.52±28.15)、(89.92±35.46)、(159.65±62.42)ng/L,与术前的(126.25±40.36)(、186.32±68.74)、(253.48±106.57)ng/L比较,均P<0.01。术后腹水较术前明显减少。[结论]TIPS能有效降低门脉压,降低血浆ET、PRA及ATⅡ的浓度,改善患者门脉系统及全身的血循环。     

Effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients

This study was undertaken to evaluate the effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients. Sixteen cirrhotics were randomly assigned to metoclopramide (10 mg i.v.) or saline. Metoclopramide significantly decreased transmural variceal pressure (15.7% decrease, p less than 0.05 vs. basal value). In order to evaluate if the metoclopramide-induced drop in transmural variceal pressure was due to an effect on portal haemodynamics, we also measured, by means of real time and pulsed Doppler ultrasonography, portal vein diameter, mean velocity of portal flow, and portal venous flow. No significant change was observed before and after metoclopramide. In conclusion, metoclopramide, which increases lower oesophageal sphincter pressure, significantly decreases transmural variceal pressure in cirrhotic patients. However, it does not have any effect on portal haemodynamics.