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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Portal and systemic hemodynamic responses to a very low dose of nitroglycerin were studied in patients with portal hypertension and cirrhosis, and compared with those to a high dose of this compound. A 0.15 mg dose of nitroglycerin was given sublingually to 10 patients (LDG), and 0.3 mg to another 10 (HDG). Hemodynamic measurements were performed by means of hepatic venous and right cardiac catheterization before and 5 min after nitroglycerin administration. The wedged hepatic venous pressure decreased after dosing by 7.9% (p < 0.01) in LDG, and by 15.3% (p < 0.01) in HDG. Hepatic blood flow with ICG did not change in either group. In LDG, azygos blood flow remained unchanged, in contrast to a significant decrease by 10.1% (p < 0.05) in HDG. Mean arterial pressure fell by 3.6% (p < 0.05) in LDG and by 18.6% (p < 0.01) in HDG. Cardiac index did not change in LDG, but decreased by 11.4% (p < 0.05) in HDG. In both groups, mean pulmonary arterial pressure and pulmonary capillary wedge pressure fell significantly by the same amount. In HDG, a significant correlation between changes in wedged hepatic venous pressure and azygos blood flow (r = 0.70, p < 0.05) was observed. This suggested that splanchnic vasoconstriction mediated by a high-pressure, rather than a low-pressure, baroreceptor reflex was the main contributor to a decrease in portal venous blood flow, resulting in a reduction in wedged hepatic venous pressure; whereas a slight but significant fall of wedged hepatic venous pressure induced by a very low dose of nitroglycerin might have been due to venodilatation in the portal system and the hepatic vascular bed. These data suggest that, even with a very low dose of nitroglycerin, partial improvement of the hepatic circulation can be expected with minimal change in the systemic circulation in patients with cirrhosis and portal hypertension.
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PMID:Portal and systemic hemodynamic responses to a very low dose of nitroglycerin in cirrhotic patients with portal hypertension. 772 74

Torsade de pointes is an unusual life-threatening ventricular arrhythmia that has been associated with vasopressin, neuroleptic drugs, and electrolyte imbalances, including hypokalemia and hypomagnesemia. Over a 9-month period, we observed torsade de pointes in three patients with cirrhosis and bleeding esophageal varices who did not have prior cardiac disease. All had received endoscopic sclerotherapy and continuous infusions of vasopressin and nitroglycerin. For sedation, two patients received haloperidol and one droperidol. In addition, two patients had either hypokalemia or hypomagnesemia. In all three patients, there was prolongation of the electrocardiographic QT interval and a "long-short" initiating sequence followed by ventricular tachycardia with torsade de pointes morphology. All were successfully cardioverted; there was one late death due to aspiration and septicemia. We conclude that cirrhotics with variceal hemorrhage may be at increased risk of developing this arrhythmia in the setting of treatment with vasopressin, sedation with neuroleptic drugs, and electrolyte abnormalities. We urge close monitoring of these patients for cardiac arrhythmia and recommend that neuroleptics be used cautiously, if at all.
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PMID:Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. 773 96

The task of pharmacotherapy in acute haemorrhage from oesophageal varices in patients with cirrhosis of the liver and portal hypertension is to arrest bleeding by reducing the blood pressure and blood flow in the oesophageal varices. The mechanism of action of the majority of drugs used is vasoconstriction of the arterioles in the splanchnic region. Somatostatin seems to be more effective and in particular safer than vasopressin, terlipressin or their combination with the vasodilatator nitroglycerin. Initial pharmacotherapy for rapid control of haemorrhage is simple and effective treatment, however, it cannot be considered an alternative of sclerotherapy, which remains the method of choice in acute haemorrhage from oesophageal varices and is effective in 90-95%. Pharmacotherapy is useful also in the prevention of relapsing haemorrhage from oesophageal varices. A combination of sclerotherapy with somatostatin or nitrates to reduce early relapses of haemorrhage is particularly effective. The effectiveness of beta-blockers to reduce the risk of relapsing haemorrhage is less clear. Prophylactic treatment for the prevention of the first haemorrhage from oesophageal varices (pharmacological, but also endoscopic or surgical) is justified only in strictly selected patients with a high risk of haemorrhage.
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PMID:[Pharmacotherapy of portal hypertension]. 776 77

Cirrhosis of the liver is associated with altered cardiovascular regulation. Patients with cirrhosis often have decreased total peripheral vascular resistance despite increased sympathetic activity. To determine whether this reduction in effective sympathetic activity may be caused by an alteration in vascular adrenergic responsiveness, we studied nine patients with biopsy-proven cirrhosis and 12 age-matched control subjects. To assess human vascular adrenergic responsiveness, we used dorsal hand vein linear variable differential transformer techniques. Sensitivity for phenylephrine-mediated vasoconstriction was significantly reduced in patients with cirrhosis (median effective dose [ED50] for phenylephrine: cirrhosis, 1514 ng/min; control subjects, 282 ng/min; p = 0.026). In contrast, the effect of isoproterenol did not differ (cirrhosis: 89% +/- 15% of maximal nitroglycerin effect; control subjects 79% +/- 6%; ED50 for isoproterenol: cirrhosis, 38 ng/min; control subjects, 20 ng/min). These studies indicate that vascular alpha-adrenergic responsiveness in patients with cirrhosis is decreased, whereas beta-adrenergic responsiveness remains intact. A selective decrease in vascular alpha-adrenergic responsiveness may contribute to the decreased peripheral vascular resistance in cirrhosis.
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PMID:Vascular alpha-adrenergic responsiveness is reduced in cirrhosis. 799 9

Between 1988 and 1990 an unblinded, randomized trial of terlipressin or vasopressin plus transdermal nitroglycerin, as part of a treatment strategy including emergency sclerotherapy for actively bleeding varices, was conducted during 165 admissions in 137 patients with cirrhosis and upper digestive bleeding. Eighty-four patient admissions were assigned to terlipressin (2 mg every 6 h) and 81 to vasopressin (0.4 to 0.8 unit per min) plus transdermal nitroglycerin (20 to 80 mg). The two groups were comparable for relevant clinical data, but there were slightly more patients with hepatocellular carcinoma or terminal conditions in the terlipressin group. After the 24-h study period, failure to control bleeding was 20/84 (25%) in the vasopressin and 14/81 (17%) in the terlipressin group (p = 0.19). Corresponding figures for patients bleeding from varices (emergency sclerotherapy in 43 and 45, respectively) were 13/55 (24%) and 5/56 (9%; p = 0.035), from other sources 5/16 (31%) and 2/15 (13%; p = 0.23), from undefined sources 2/10 (20%) and 7/13 (54%; p = 0.1). In a logistic multivariate regression model the odds ratio for terlipressin adjusted for prognostic factors was 0.45 (p = 0.07). There were seven major side effects requiring treatment discontinuation in the vasopressin and one in the terlipressin group. These results suggest that terlipressin alone is as effective as vasopressin plus transdermal nitroglycerin, with less severe side effects, in 24-h control of upper gastrointestinal bleeding in patients with cirrhosis.
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PMID:Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis. A randomized clinical trial. Liver Study Group of V. Cervello Hospital. 800 1

We studied 30 patients with cirrhosis to determine the effect of nitroglycerin on portal and gastric mucosal hemodynamics. Systemic hemodynamics, portal venous pressure (PVP), the hemoglobin index (IHB), and the oxygen saturation index (ISO2) of the gastric mucosa were measured before and after a continuous infusion of nitroglycerin. The patients were divided into two groups according to the presence or absence of major portal-systemic collateral routes on portograms. Nitroglycerin caused a reduction in PVP in all patients. Although there was no significant difference in systemic hemodynamic changes between the two groups, the reduction in PVP in patients with major portal-systemic collaterals was significantly higher than in those without major collaterals. A nitroglycerin infusion, at a dose of 1.0 micrograms/kg per min for 10 min, produced a reduction in both IHB (-16%, P < 0.001) and ISO2 (-13%, P < 0.001) in the gastric mucosa, indicating gastric mucosal ischemia secondary to splanchnic vasoconstriction. These findings suggest that the continuous infusion of nitroglycerin reduces PVP in cirrhotic patients, particularly in those with major portal-systemic collaterals, and reduces the congestion of the gastric mucosa in patients with portal hypertension.
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PMID:Influence of nitroglycerin on portal pressure and gastric mucosal hemodynamics in patients with cirrhosis. 801 7

Pharmacological management of acute variceal hemorrhage appears to be effective in patients with liver cirrhosis. Somatostatin and presumably its longer-acting analog, octreotide, are more efficient and safer than other vasoconstrictors like vasopressin, terlipressin or their combination with nitroglycerin. Drug treatment, however, usually represents only a valuable adjunct to other measures to stop bleeding such as endoscopic variceal sclerotherapy. Prophylaxis of first bleeding by beta-blockade appears justified in patients at a high risk of bleeding which still has to be defined more precisely. Prevention of recurrent hemorrhage can be effective in some but not in all of the patients with liver cirrhosis and a first bleeding episode. Treatment of patients with good liver function under direct control of the wedged hepatic vein pressure gradient presumably will reduce the failure rate of prophylaxis with beta-blockade.
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PMID:The role of drug treatment in variceal bleeding. 811 90

We undertook a multicenter randomized trial to compare the efficacy of terlipressin combined with transdermal nitroglycerin and that of octreotide in the emergency control of acute variceal hemorrhage in cirrhosis. Over 16 mo, 87 patients with endoscopically proved active bleeding from esophageal or cardiac varices were enrolled in five centers in France and randomly assigned to receive intravenous terlipressin (2 mg and then 1 mg/4 hr over 24 hr) and transdermal nitroglycerin (10 mg/12 hr over 24 hr) (group 1) or octreotide (continuous intravenous infusion of 25 micrograms/hr over 12 hr and then 100 micrograms at hr 12 and hr 18 subcutaneously) (group 2). Initial control of bleeding was assessed at the end of 12 hr of treatment on the basis of stability of blood pressure and hematocrit level with no further transfusion requirements. At 12 hr, bleeding was controlled in 59% (24 of 41) in group 1 and 78% (36/46) of group 2 patients (Fisher's exact test, p = 0.064). Mean transfusion requirements over this 12-hr period were significantly greater in group 1 (three blood units; range = 0 to 13) than in group 2 (one blood unit; range = 0 to 5) (p = 0.002). After the first 12 hr, 20% of patients (5 of 24) had repeat bleeding in group 1 compared with 27% (10 of 36) in group 2. During the first 48-hr period, five patients (12%) died in group 1, compared with 3 (6%) in group 2. Few side effects were noted in either group. However, in group 1 two patients experienced severe bradycardia; it resulted in death in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Terlipressin plus transdermal nitroglycerin vs. octreotide in the control of acute bleeding from esophageal varices: a multicenter randomized trial. 832 22

We studied the hemodynamic changes following a four-week administration of either low-dose transdermal nitroglycerin (a constant release of 5 mg of nitroglycerin/day) (N = 10) or low-dose transdermal nitroglycerin plus spironolactone (100 mg/day) (N = 9) in patients with cirrhosis and portal hypertension. Two patients in the latter group did not undergo repeat measurements after dropping out because of severe headaches or developing ascites during the study. Transdermal nitroglycerin induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-11.7 +/- 14.9%, P < 0.05), which was associated with a significant reduction of cardiac output (-10.5 +/- 7.3%). Nitroglycerin plus spironolactone induced a significant reduction in the HVPG (-18.3 +/- 16.0%, P < 0.05) associated with a significant reduction of cardiac output (-13.8 +/- 5.6%), right atrial pressure (-35.0 +/- 30.0%), mean arterial pressure (-7.5 +/- 6.8%), and plasma volume (-10.2 +/- 7.0%). The difference of the mean HVPG reduction between the groups was insignificant. A decrease in the HVPG greater than 10% was observed in six of 10 patients (60%) and in five of seven patients (71.4%), defined as "responders," at four weeks. The difference in percentage of responders between the groups was insignificant. We found that in some cirrhotic patients, low-dose transdermal nitroglycerin is potentially useful in the treatment of portal hypertension. Spironolactone as an adjunct to low dose transdermal nitroglycerin did not demonstrate therapeutic advantages in the treatment of portal hypertension in cirrhotics. That there were nonresponders indicates that there are variable responses in splanchnic hemodynamics to these drugs.
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PMID:Chronic splanchnic hemodynamic effects of low-dose transdermal nitroglycerin versus low-dose transdermal nitroglycerin plus spironolactone in patients with cirrhosis. 907 34

The therapy of portal hypertension depends to a significant extent on its clinical manifestation. In cases of acute haemorrhage from oesophageal varices in patients with portal hypertension, the objective of the therapy is to stop the haemorrhage (endoscopically, or by compression by means of a balloon probe) and to decrease the pressure and the reflux within the portal vascular bed. Urgent sclerotisation under the simultanous pharmacologic decrease of portal hypertension is successful in 93-95%. There is an alternative procedure residing in introducing a balloon probe for several hours and subsequent repeated sclerotisation until a complete eradication of varices is achieved regarding the prevention of haemorrhage exacerbation. Urgent surgical solution is on the basis of the results of various investigated studies reserved for patients in whom endoscopic sclerotisation was not successful. Indication of surgical therapy must be also deliberated in candidates for liver transplantation, regarding the possible consequent technical problems after some types of interventions. Endoscopic sclerotisation of oesophageal varices is also an appropriate preparation for transplantation of the liver in patients with liver cirrhosis included into the transplantation programme. TIPS is a perspective new method in the therapy of portal hypertension of both, non-bleeding varices, as well as in other indications. It is also a certain intermediating link in therapy in some patients with liver cirrhosis on the waiting list of candidates for liver transplantation. Pharmacotherapy is a significant part of the portal hypertension therapy. It is appropriate to combine the endoscopic treatment with pharmacotherapy of portal hypertension in both, cases of acute haemorrhage, as well as in the prevention of haemorrhage exacerbation. In cases of acute haemorrhage, the combination of glypressin with nitroglycerin is justified, as well as the therapy by somatostatin. The prevention of haemorrhage exacerbations uses a whole series of vasoactive substances, especially nitrates, beta-blockers and ACE inhibitors. The prevention of the first bleeding includes the prophylactic therapy (endoscopic, pharmacologic, or surgical) recommended only in a selected group of patients under high risk of bleeding. The possible perspective option will reside especially in the combined pharmacological therapy, the fact of which will have to be proven in the future. (Fig. 1, Ref. 25.)
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PMID:[Treatment of portal hypertension]. 958 83


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