David Kravetz

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.

Measurement of azygos venous blood flow in the evaluation of portal hypertension in patients with cirrhosis: Clinical and haemodynamic correlations in 100 patients*

Blood flow in the azygos vein, an index of blood flow through gastro-oesophageal collaterals, was measured by continuous thermal dilution in 100 patients with cirrhosis. Azygos blood flow was directly related to portal pressure (r = 0.54, P less than 0.001). Patients with portal hypertension had very high azygos blood flow (692 +/- 32 ml/min) in comparison with controls (n = 11, 174 +/- 29 ml/min). Patients with previous oesophageal bleeding had similar azygos blood flow as those without, but azygos blood flow was significantly greater in patients with massive or recurrent bleeding than in those with less severe haemorrhage, suggesting that the magnitude of collateral flow may influence the course of variceal bleeding. Patients with grade III varices had higher azygos blood flow than those with grades II or I. In addition, both oesophageal tamponade and vasopressin infusion, procedures of known value in variceal bleeding, markedly reduced azygos blood flow (-40% and -25%, respectively). Measurement of azygos blood flow allows evaluation of haemodynamic changes in the oesophageal collaterals of patients with portal hypertension, and provides useful information on the effect of therapeutic procedures aimed at arresting or preventing variceal haemorrhage.

Effects of prostaglandin inhibition on systemic and hepatic hemodynamics in patients with cirrhosis of the liver

The role of prostaglandins in the pathogenesis of the circulatory abnormalities of cirrhosis was investigated by studying the effects of prostaglandin inhibition with indomethacin (50 mg/8 h for 24 h) on the systemic and splanchnic hemodynamics in 13 patients with cirrhosis of the liver. Indomethacin administration significantly reduced cardiac output (from 7.44 +/- 0.7 to 6.78 +/- 0.7 L/min, p less than 0.05) and increased peripheral vascular resistance (from 990 +/- 104 to 1155 +/- 140 dyn X s X cm-5, p less than 0.05). Arterial pressure was not modified. These changes in systemic hemodynamics were associated with a significant reduction in hepatic blood flow (from 1.88 +/- 0.43 to 1.48 +/- 0.3 L/min, p less than 0.05) and with a slight decrease of portal pressure (from 18.8 +/- 1.3 to 17.5 +/- 1.4 mmHg, p less than 0.05). These results suggest that endogenous prostaglandins contribute to the increased cardiac output and diminished vascular resistance observed in cirrhosis of the liver. In addition, by promoting splanchnic vasodilation, prostaglandins may contribute to increased portal pressure in these patients.

Plasma Renin Activity and Urinary Sodium Excretion as Prognostic Indicators in Nonazotemic Cirrhosis with Ascites

Azotemia is an ominous prognostic sign in cirrhosis with ascites. To investigate whether other renal disturbances are also prognostically significant, we studied the renin-aldosterone system and sodium excretion (UNaV) in 75 patients who had nonazotemic cirrhosis with ascites and related these to survival. On the basis of plasma renin activity patients were classified in two groups. Group I included 34 patients with normal renin activity (1.13 +/- 0.69 ng/mL . h) and Group II, 41 patients with high renin activity (7.46 +/- 3.86 ng/mL . h). The two groups differed significantly (p less than 0.001) in plasma aldosterone, UNaV, and wedged hepatic venous pressure but not in clinical features, liver function, glomerular filtration, and renal plasma flow. Patients of Group I lived significantly longer than those of Group II (the 50% survival rates were 28 months and 6 months, respectively). Survival curves obtained after grouping the patients according to UNaV (higher and lower than 10 meq/d) were almost identical to those obtained according to renin activity. The study results indicate that plasma renin activity and UNaV are of prognostic value in nonazotemic cirrhosis with ascites.

Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites: Results of a randomized study

Forty-one patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g for each 1000 ml of ascites removed) (group I = 20 patients) or paracentesis with albumin (6 g for each 1000 ml of ascites) (group II = 21 patients). The basal clinical features, laboratory data, and plasma renin activity were similar in both groups. The volume of ascites removed was 12.9 +/- 4.4 and 10.9 +/- 3.7 liters in group I and II, respectively (n.s.). No significant changes were observed in liver and renal function tests, KPTT, platelet count, factor VIII, serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups, except for a decrease in bilirubin in group I and a transient increase of serum albumin in group II. Four patients developed complications in each group, mainly hyponatremia, while one patient in each group developed renal impairment. One patient from group I died with hepatic encephalopathy. Moreover, the probability of survival and readmission to the hospital because of tense ascites were similar in both groups of patients during the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient treated. These results indicate that repeated large volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites. However, due to its reduced cost, paracentesis with Dextran 70 may be considered the treatment of choice in cirrhotic patients with tense ascites without liver cancer and renal failure.

Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis

The effects of beta-blockade with propranolol and of alpha-adrenergic stimulation with methoxamine, a powerful alpha-agonist, on azygos blood flow and on systemic and hepatic haemodynamics were investigated in 26 cirrhotic patients with portal hypertension. Beta-adrenergic blockade with propranolol (n = 12), evidenced by a significant reduction of heart rate (-17 +/- 1%, P less than 0.001) and cardiac index (-17 +/- 2%, P less than 0.001), caused a mild but significant decrease of hepatic venous pressure gradient (-10 +/- 2%, P less than 0.05) and a marked fall of azygos venous blood flow (-31 +/- 5%, P less than 0.05). Alpha-adrenergic stimulation with methoxamine (n = 14), manifested by a significant increase of mean arterial pressure (19 +/- 2%, P less than 0.001), mimicked the effects of propranolol on hepatic venous pressure gradient (-10 +/- 4%, P less than 0.05) and cardiac index (-11 +/- 2%, P less than 0.001). However, azygos blood flow was not significantly reduced by methoxamine (0.7 +/- 0.1 vs 0.6 +/- 0.1 l/min). On the contrary, hepatic blood flow was significantly reduced by methoxamine (-19 +/- 4%, P less than 0.01) but not by propranolol (-7 +/- 7%, ns). Similarly, in 8 patients who received methoxamine after being beta-blocked by propranolol, azygos blood flow, that was markedly reduced by beta-blockade, did not experience a further reduction but increased slightly by alpha-adrenergic stimulation, while hepatic blood flow, that was not reduced by propranolol, decreased significantly during the subsequent methoxamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Somatostatin in Patients with Portal Hypertension

Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.