Measurement of azygos venous blood flow by a continuous thermal dilution technique: an index of blood flow through gastroesophageal collaterals in cirrhosis

A method to quantitate blood flow through the gastroesophageal collaterals in portal hypertensive patients was developed. Since gastroesophageal collaterals drain into the azygos system, it is postulated that measurement of blood flow in the azygos vein should provide a quantitative measurement of gastroesophageal collateral blood flow changes in portal hypertensive patients. Azygos blood flow was measured using a double thermodilution catheter directed under fluoroscopy to the azygos vein. Ten patients with alcoholic cirrhosis were studied. Five of these patients had a history of repeated bleeding from gastroesophageal varices (Group I). The azygos blood flow in these patients was 596 +/- 78 ml per min. The other five patients all had decompressive surgery of the portal system (Group II). In these patients the azygos venous blood flow was 305 +/- 29 ml per min (p less than 0.01). The coefficient of variation of repeated baseline measurements was of 4.4 +/- 0.6%. The azygos venous blood flow measurement is a rapid, simple and sensitive method to evaluate blood flow changes in the vessels involved in gastroesophageal bleeding due to portal hypertension.     

Influence of the sclerosing of esophageal varices on portal pressure and azygos venous blood flow

Endoscopic sclerotherapy is widely employed for esophageal variceal hemorrhage. However it has side effects and can aggravate portal hypertension by suppression of portosystemic shunt. The purpose of the present investigation was to study the effect of variceal thrombosis on hepatic venous pressure gradient and azygos blood flow. Eight alcoholic cirrhotic patients with a first variceal hemorrhage were included. According to Child Pugh's classification, 4 patients were group A, 2 group B and 2 group C. At each session 40 to 60 ml of 1 p. 100 polidocanol were injected into the varices. A hemodynamic study was performed in each patient before and about one week after variceal obliteration (mean 3.3 procedures). Mean value of hepatic venous pressure gradient was 16.6 +/- 5.5 mm Hg and 17.0 +/- 3.8, respectively, before sclerotherapy and after eradication of varices; azygos blood flow 663 +/- 506 ml/mn before and 682 +/- 522 after; cardiac, output was 6.5 +/- 0.7 ml/min before and 6.5 +/- 0.8 after. None of these differences were significant. These results suggest that endoscopic sclerotherapy using polidocanol does not change hepatic venous pressure gradient and azygos blood flow, and does not lower blood flow through the gastroesophageal collaterals draining into the azygos vein. This is consistent with the hypothesis that thrombosis remains localized.     

Superior portosystemic collateral circulation estimated by azygos blood flow in patients with cirrhosis. Lack of correlation with oesophageal varices and gastrointestinal bleeding. Effect of propranolol

In patients with cirrhosis, superior portosystemic collateral circulation was evaluated by the continuous thermodilution method in the azygos vein. Azygos blood flow was 5 times higher in a group of patients with cirrhosis (alcoholic in 27, cryptogenic in 8, post-hepatitic in 2 and primary biliary cirrhosis in 1), than in a group of patients without portal hypertension (steatosis in 2, granulomatous hepatitis in 2, persistent chronic hepatitis in 2 and Hodgkin's disease in 1). Azygos blood flow was not different in cirrhotic patients with no visible, in those with small-sized, and in those with large sized oesophageal varices. Azygos blood flow was not different in cirrhotic patients with and without a previous episode of gastrointestinal bleeding. Fifteen min after intravenous administration of 15 mg of propranolol, azygos blood flow significantly decreased whereas azygos blood flow did not change after placebo. The decrease in azygos blood flow was significantly more marked than the reduction in cardiac output. It is concluded that superior portosystemic collateral blood flow is elevated in patients with cirrhosis and that the reduction in this collateral circulation might explain the efficiency of propranolol in the prevention of recurrent gastrointestinal bleeding.     

Oxygen and bile acid content in the azygos blood. Clues to the azygos derivation in patients with portal hypertension

In patients with cirrhosis, elevation of azygos blood flow has been attributed on indirect grounds to cephalad portosystemic collaterals. To gather more information on the origin of the azygos blood, we studied the oxygen and bile acid content of the azygos and mixed venous blood in patients with portal hypertension. Azygos oxygen saturation was 59.6 +/- 6.0% in 8 controls, and significantly higher in 35 patients with cirrhosis (76.7 +/- 7.6%; P less than 0.01) as well as in 6 patients with noncirrhotic portal hypertension (84.0 +/- 8.2%; P less than 0.01). High oxygen saturation, however, was not correlated to azygos blood flow in patients with cirrhosis. In cirrhotic patients, total bile acid concentrations were 28.1 +/- 20.4 mumol/l in the pulmonary artery and 25.9 +/- 17.6 mumol/l in the azygos vein, giving an azygos to mixed venous ratio of 0.95 +/- 0.18. These results provide new evidence that elevated azygos blood flow in patients with portal hypertension is derived from the portal system, and perhaps predominantly from the splenic territory.     

Noninvasive measurement of the pressure of esophageal varices using an endoscopic gauge: comparison with measurements by variceal puncture in patients undergoing endoscopic sclerotherapy

Measurements of variceal pressure with a noninvasive endoscopic pressure gauge and by direct variceal puncture were performed in 20 cirrhotic patients with portal hypertension in the course of the first session of therapeutic sclerotherapy following an episode of variceal bleeding. Endoscopic gauge measurements of the pressure of esophageal varices gave similar values (15.5 +/- 2.7 mm Hg) than measurements by variceal puncture (15.4 +/- 2.4 mm Hg; not statistically significant), and there was a highly significant linear correlation between both measurements (r = 0.9, p less than 0.001). Azygos blood flow, that was markedly increased in these patients (852 +/- 399 ml per min), was directly related to variceal pressure (r = 0.73, p less than 0.01). Variceal pressure was significantly lower than portal pressure (18.8 +/- 5.0 mm Hg) (p less than 0.05), indicating that measurements of variceal pressure cannot substitute measurements of portal pressure. The study demonstrates that the noninvasive endoscopic gauge technique allows an accurate estimation of variceal pressure in patients with portal hypertension. This technique may provide additional useful information in the evaluation of portal hypertension as well as on the mechanism of variceal bleeding.     

Evaluation of the blood flow of superior portacaval anastomoses by the measurement of azygos blood flow in patients with alcoholic cirrhosis

In patients with portal hypertension the azygos system collects the main part of superior portosystemic shunts; accordingly, azygos blood flow might be a reflection of this collateral circulation. Azygos blood flow, estimated by the continuous thermodilution method with a catheter inserted into the azygos arch, was measured in 20 patients with cirrhosis. The variability of baseline measurements was 6.9 +/- 3.0 p. 100 and the reproducibility was 5.7 +/- 5.8 p. 100. In patients with cirrhosis, azygos blood flow ranged from 0.22 to 1.25 l/min (0.64 /+- 0.30 l/min; mean +/- SD) and was significantly higher than in patients without portal hypertension (0.13 +/- 0.04 l/min). In this series of patients, azygos blood flow was significantly correlated with the hepatic venous pressure gradient but neither with hepatic blood flow nor with cardiac output. This study shows that azygos blood flow may be estimated with the continuous thermodilution method and that azygos blood flow is approximately six times higher in cirrhotic patients than in controls. This result suggests that blood flow through the superior portosystemic shunts is very high.     

The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis

BACKGROUND: In cirrhosis, repeated flares of portal pressure and collateral blood flow provoked by postprandial hyperaemia may contribute to variceal dilation and rupture. AIM: To examine the effect of the extent of the collateral circulation on the postprandial increase in portal pressure observed in cirrhosis. PATIENTS AND METHODS: The hepatic venous pressure gradient (HVPG), hepatic blood flow and azygos blood flow were measured in 64 patients with cirrhosis before and after a standard liquid meal. RESULTS: Peak increases in HVPG (median+14.9%), hepatic blood flow (median+25.4%), and azygos blood flow (median+32.2%) occurred at 30 min after the meal. Compared with patients with marked postprandial increase in HVPG (above the median, n = 32), those showing mild (<15%, n = 32) increase in HVPG had a higher baseline azygos flow (p<0.01) and underwent a greater postprandial increase in azygos flow (p<0.02). Hepatic blood flow increased similarly in both groups. Postprandial increases in HVPG were inversely correlated (p<0.001) with both baseline azygos flow (r = -0.69) and its postprandial increase (r = -0.72). Food intake increased nitric oxide products in the azygos (p<0.01), but not in the hepatic vein. Large varices (p<0.01) and previous variceal bleeding (p<0.001) were more frequent in patients with mild increase in HVPG. CONCLUSIONS: Postprandial hyperaemia simultaneously increases HVPG and collateral flow. The extent of the collateral circulation determines the HVPG response to food intake. Patients with extensive collateralisation show less pronounced postprandial increases in HVPG, but associated with marked flares in collateral flow. Collateral vessels preserve their ability to dilate in response to increased blood flow.     

Effects of non-shunting operation on azygos venous blood flow in cirrhotic patients.

Azygos venous blood flow and other haemodynamic parameters were measured in 14 cirrhotic patients to investigate the effects of a non-shunting operation, oesophageal transection with paraoesophagogastric devascularisation. Azygos venous blood flow measured by the local continuous thermal dilution method was significantly reduced by 13.8% after the operation (428 (41) v 369 (33) ml/min). Hepatic venous pressure gradient (HVPG) was also significantly decreased from 14.5 (0.8) to 12.8 (0.7) mmHg (-11.8%). Cardiac output and routine liver tests did not change remarkably postoperatively. In this haemodynamic study before and after non-shunting operation, moderate but significant decreases were seen in azygos venous blood flow and portal pressure (HVPG), without substantial changes in systemic circulation. This suggests that blood flow through the portosystemic collaterals other than oesophageal varices may be decreased but still adequate after the operation. Well preserved portosystemic collaterals without oesophageal varices are thus considered an optimally balanced state after non-shunting operation.     

Effect of metoclopramide on portal blood flow in patients with liver cirrhosis, measured by the pulsed Doppler system

The effect of metoclopramide on portal blood flow, the maximal diameter of the portal vein, and some cardiovascular haemodynamic variables was studied in 10 patients with cirrhosis of the liver and portal hypertension. Portal vein haemodynamics were studied by the pulsed Doppler system. Within 15 min of intravenous administration of 20 mg metoclopramide, portal blood velocity and portal blood flow decreased significantly, from 11.2 +/- 1.1 to 10.8 +/- 1.2 cm/sec and from 769.0 +/- 87.7 to 707.9 +/- 84.2 ml/min, respectively (p less than 0.001). Within about 30 min portal blood velocity and portal blood flow returned to basal values (p greater than 0.05). The maximal diameter of the portal vein, systolic and diastolic blood pressure, and heart rate remained unchanged. These results support the hypothesis that metoclopramide, which raises lower oesophageal sphincter pressure and reduces intravariceal blood flow, significantly decreases the portal blood flow in cirrhotic patients with portal hypertension.     

Hyperkinetic circulatory syndrome in patients with presinusoidal portal hypertension : Effect of propranolol

This study evaluates systemic and splanchnic haemodynamics and the effect of propranolol in 15 patients with presinusoidal portal hypertension (portal vein obstruction, n = 11; schistosomiasis, n = 4). These patients exhibited a hyperkinetic circulatory syndrome characterized by high cardiac index (4.4 +/- 1.61.min-1.m-2, mean +/- S.D.) and by low systemic vascular resistance despite normal liver function and sinusoidal pressure. Hepatic blood flow was decreased in half of the patients with portal vein obstruction. Azygos blood flow, an estimate of superior portal-systemic collateral circulation, was markedly increased in all patients (0.46 +/- 0.19 l/min, upper limit of normal: 0.19 l/min). Therefore, in these patients with normal hepatic venous pressure gradient, azygos blood flow measurement provides an index of splanchnic haemodynamic changes. Propranolol administration (15 mg, i.v.) reduced the hyperkinetic circulatory syndrome, with a significant decrease in heart rate (-17 +/- 6%), cardiac index (-25 +/- 12%) and azygos blood flow (-40 +/- 26%) and a significant increase in systemic vascular resistance (+40 +/- 40%). These results suggest that the hyperkinetic circulatory syndrome observed in these patients, could be related to an increase in beta-adrenergic activity. The decrease in azygos blood flow, after propranolol administration, was significantly correlated (r = 0.94) with the increase in right atrial pressure. This finding suggests that propranolol may act through an increase in portal-systemic collateral venous tone. These haemodynamic results justify, in patients with presinusoidal portal hypertension, clinical trials investigating the beneficial effect of beta-blockers on gastrointestinal bleeding caused by portal hypertension.     

Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study.

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.     

Reversal of adrenaline-induced increase in azygos blood flow in patients with cirrhosis receiving propranolol

In patients with cirrhosis, endogenous catecholamines may influence the circulatory effects of propranolol. We intended to evaluate the interaction of adrenaline and propranolol on azygos blood flow, an estimate of blood flow in the superior portosystemic collateral circulation. We investigated 6 patients with cirrhosis, 5 with good liver function, receiving an intravenous infusion of adrenaline (50 ng/kg/min) before and after administration of propranolol. The median value for baseline azygos blood flow was increased from 700 ml/min (range 340-1 470 ml/min) to 1 050 (range 570-1 840 ml/min) with adrenaline alone (P less than 0.05), and decreased to 610 ml/min (range 260-1 190 ml/min) with propranolol alone (P less than 0.05). The infusion of adrenaline given after propranolol further reduced azygos blood flow to a median value of 530 ml/min (range 200-730 ml/min) (P less than 0.05). Thus, following beta-adrenergic blockade, there is a reversal of the effects of adrenaline on azygos blood flow, which corresponds to a potentiation of the effects of propranolol. Similar endogenous adrenaline-propranolol interactions may play a role in preventing recurrent variceal bleeding in cirrhotic patients.     

The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy

In addition to variceal bleeding, haematemesis may occur due to haemorrhagic gastritis in patients with portal hypertension. This has been known as portal hypertensive gastropathy (PHG). We have evaluated the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on portal venous pressure (PVP) and endoscopic gastric mucosal changes observed in patients with portal hypertension. We performed TIPS in 12 patients with complications due to portal hypertension as follows: variceal bleeding in nine patients (bleeding from oesophageal varices in seven and gastric varices in two), refractory ascites in three and haemorrhage from severe PHG in one. Endoscopic examinations were performed before and after TIPS for all patients. Changes of PVP and gastric mucosal findings on endoscopy were analysed. Before TIPS, PHG was seen in 10 patients. Portal venous pressure decreased from an average of 25.1 ± 8.8 to 17.1 ± 6.2 mmHg after TIPS ( P < 0.005). On endoscopy, PHG improved in nine of 10 patients. Oesophagogastric varices improved in eight of 11 patients. In one patient with massive haematemesis, haemorrhage from severe PHG completely stopped after TIPS. Because TIPS effectively reduced PVP, this procedure appeared to be effective for the treatment of uncontrollable PHG.     

Endoscopic measurement of variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage

This study evaluated the clinical application of a pressure-sensitive gauge that allows the noninvasive measurement of the pressure of esophageal varices at endoscopy. The study was performed in 70 patients with cirrhosis and portal hypertension. Among them, 47 had bled from the varices and 23 had varices but had not bled. In addition to measurements of variceal pressure, the size of the varices was estimated semiquantitatively at endoscopy. This allowed an estimate of the tension on the wall of the varices as the product of the transmural pressure and the estimated radius of the varices. Most patients had a standard hemodynamic evaluation of portal hypertension, with measurements of wedged and free hepatic venous pressures, and of azygos blood flow. These were performed within 24 h of the variceal pressure measurements. Variceal pressure was significantly higher in bleeders than in nonbleeders (15.7 +/- 2.8 vs. 12.1 +/- 2.6 mmHg, p less than 0.001) in spite of a similar portal pressure in both groups (20.1 +/- 5.1 vs. 20.4 +/- 7.6 mmHg, NS). More than 60% of the bleeders, but only 22% of the nonbleeders had a variceal pressure greater than or equal to 15 mmHg (p less than 0.005). Among nonbleeders, variceal pressure was higher in patients with large varices (13.9 +/- 2 mmHg, n = 9) than in those with small varices (10.9 +/- 2.4 mmHg, n = 14) (p less than 0.01). Estimates of variceal wall tension further exaggerated the differences between bleeders and nonbleeders (66.1 +/- 22.6 vs. 32.0 +/- 19.8 mmHg.mm, p less than 0.001). More than 50% of bleeders, but just 9% of nonbleeders had an estimated variceal tension greater than 50 mmHg.mm (p less than 0.001). Our findings support the role of an increased variceal pressure in the pathogenesis of variceal hemorrhage, and suggest that this noninvasive technique can be valuable in assessing the risk of variceal hemorrhage in patients with portal hypertension.     

What's new in portal hypertension?

Portal hypertension is defined as increased pressure in the portal venous system. The most common cause of portal hypertension is cirrhosis. In this setting, there is an increase in intrahepatic resistance leading to an increase in portal pressure. By increasing portal blood flow, splanchnic vasodilation further aggravates portal hypertension. New pathogenic pathways are being established which might result in new therapeutic strategies. The presence of varices at endoscopy and/or other abdominal portosystemic collaterals confirms the diagnosis of portal hypertension. The role of non‐invasive and imaging tests in the diagnosis and prognosis of portal hypertension has been clarified. Non‐selective beta‐blockers decrease both the risk of variceal haemorrhage and hepatic decompensation. Terlipressin, somatostatin or octreotide, in combination with early endoscopic therapy, are recommended for the treatment of acute variceal haemorrhage. Early Transjugular intrahepatic portosystemic shunt (TIPS) is effective as salvage therapy in acute variceal bleeding in selected patients and prevents rebleeding more effectively than endoscopic and medical therapy resulting in an increased survival.     

Longterm outcome after injection sclerotherapy for oesophageal varices in children with extrahepatic portal hypertension.

A consecutive series of 36 children with bleeding from oesophageal varices secondary to extrahepatic portal hypertension was successfully treated by endoscopic injection sclerotherapy and followed up over a mean period of 8.7 years after variceal obliteration. There were no deaths from portal hypertension or its treatment and morbidity related to oesophageal sclerotherapy was minimal. Endoscopic injection sclerotherapy alone proved safe and effective in controlling variceal bleeding from portal hypertension in over 80% of the children. Recurrent variceal bleeding developed in 10 (31%) patients but half of these were effectively treated by further sclerotherapy. Gastric variceal bleeding unresponsive to sclerotherapy necessitated successful portosystemic shunt surgery in four (13%) patients. Two children required splenectomy for painful splenomegaly. In most children injection sclerotherapy is the best treatment for the primary management of bleeding oesophageal varices, reserving portosystemic shunting or other surgical procedures for those with bleeding from gastrointestinal varices.     

Pattern of upper gastrointestinal haemorrhage in northern India—An endoscopic study of 316 patients

Three hundred and sixteen patients with acute upper gastrointestinal haemorrhage were studied prospectively and consecutively. The most frequent cause was variceal bleeding due to portal hypertension (36%), followed by peptic ulceration (24%) and gastric erosions (19%). Variceal haemorrhage tended to be severe and had a high individual mortality rate. Associated acute mucosal lesions with portal hypertension were strikingly less frequent when compared with the experience from the West. Seven per cent of patients died of bleeding alone and an equal number of an associated systemic disorder or complication. Splenomegaly was present in all patients with a variceal haemorrhage due to non-cirrhotic portal hypertension. However, in patients with portal hypertension due to cirrhosis splenomegaly was present in 63%. Endoscopy altered the clinical diagnosis in 13.2% of patients. Based on previous experience oesophago-gastro-duodenal endoscopy has been a useful tool in the management of acute upper gastrointestinal haemorrhage.     

Splanchnic Hemodynamics in Idiopathic Portal Hypertension: Comparison with Chronic Persistent Hepatitis

A comparative study of splanchnic hemodynamics was made in 12 patients with idiopathic portal hypertension and in eight patients with chronic persistent hepatitis, but without portal hypertension, who served as the control. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, and organ volume by computed tomography. Splenic artery blood flow was 788 +/- 242 ml/min in idiopathic portal hypertension and about four times that in chronic persistent hepatitis (215 +/- 42 ml/min), whereas there was no difference in superior mesenteric artery blood flow between the former and the latter (408 +/- 142 vs. 389 +/- 32 ml/min). Spleen volume in idiopathic portal hypertension was six times that in chronic persistent hepatitis, and splenic artery blood flow showed a significant linear correlation with spleen volume in idiopathic portal hypertension (r = 0.71, p less than 0.02). The sum of splenic artery blood flow and superior mesenteric artery blood flow in idiopathic portal hypertension was 1195 +/- 294 ml/min, twice that in chronic persistent hepatitis (603 +/- 109 ml/min). Portal vascular resistance and intrahepatic portal vascular resistance were three times and four times those in chronic persistent hepatitis, respectively. These results indicate that both increased intrahepatic portal vascular resistance and increased splenic artery blood flow may play roles in the development of portal hypertension in idiopathic portal hypertension.     

Endoscopic sclerotherapy in children

Thirty-eight children, aged 1-15 years, with portal hypertension and recent variceal bleeding, were treated with repeated endoscopic sclerotherapy. Thirty-six of them had extrahepatic portal venous obstruction. Obliteration of varices was achieved in 35 (92%) patients requiring an average of 5.3 sessions per patient. Major complications occurred in seven patients, three of whom had oesophageal perforations and four had oesophageal stricture. Sclerotherapy significantly reduced the rate of rebleeding after the start of sclerotherapy and more so after variceal obliteration.     

Per rectal portal scintigraphy as a useful tool for predicting esophageal variceal bleeding in cirrhotic patients

AIM： To investigate potential roles of per rectal portal scintigraphy in diagnosis of esophageal varices and predicting the risk of bleeding. METHODS： Fifteen normal subjects and fifty cirrhotic patients with endoscopically confirmed esophageal varices were included. Patients were categorized into bleeder and non-bleeder groups according to history of variceal bleeding. All had completed per rectal portal scintigraphy using ^99mTechnetium pertechnetate. The shunt index was calculated from the ratio of ^99mTechnetium pertechnetate in the heart and the liver. Data were analyzed using Student＇s t-test and receiver operating characteristics. RESULTS： Cirrhotic patients showed a higher shunt index than normal subjects （63.80 ± 25.21 vs 13.54 ± 6.46, P 〈 0.01）. Patients with variceal bleeding showed a higher shunt index than those without bleeding （78.45 ± 9.40 vs 49.35 ± 27.72, P 〈 0.01）. A shunt index of over 20% indicated the presence of varices and that of over 60% indicated the risk of variceal bleeding. CONCLUSION： In cirrhotic patients, per rectal portal scintigraphy is a clinically useful test for identifying esophageal varices and risk of variceal bleeding.