pituitrin and Liver-Cirrhosis--Alcoholic

A 73-year-old man with alcoholic liver cirrhosis was admitted to our hospital because of massive hematemesis. He was treated with continuous intravenous infusion of vasopressin of 0.2 U/min. 22 hours after the infusion, he complained of myalgia, muscle weakness and skin mottling in the extremities. The skin lesion extended to the back. The serum CK and myoglobin levels were elevated to 52,280 IU/L and 84,400 ng/ml respectively. The urinary myoglobin level was elevated to 732,000 ng/ml. On the fifth hospital, he died of bleeding from the esophageal varices. Autopsy examination demonstrated necrosis of the skeletal muscle cells and myoglobin casts in the renal tubules. Our patient was probably hypersensitive to vasopressin because of underlying liver dysfunction. The massive myonecrosis might be induced from the following conditions; overreactive vasopressin-induced vasoconstriction resulted in ischemic muscle damage, and hypersensitive sarcoplasmic reticulum released excessive Ca2+ followed by muscle hypercontraction as seen in malignant syndrome or malignant hyperthermia.

Topics: Aged; Esophageal and Gastric Varices; Humans; Infusions, Intravenous; Liver Cirrhosis, Alcoholic; Male; Muscle, Skeletal; Necrosis; Rhabdomyolysis; Vasopressins

We describe the case of a patient with hepatic cirrhosis treated with an intravenous infusion of vasopressin to control an upper digestive hemorrhage, who developed distance cutaneous necrosis and rhabdomyolysis. We review the other cases published in the international scientific literature and we discuss the possible pathogeny of these complications.

Topics: Gastrointestinal Hemorrhage; Humans; Infusions, Intravenous; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Necrosis; Rhabdomyolysis; Skin; Vasopressins

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephal

Topics: Acute Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Portacaval Shunt, Surgical; Radiography; Recurrence; Sclerosing Solutions; Vasopressins

Topics: Adrenocorticotropic Hormone; Brain; Calcifediol; Calcium; Chronic Disease; Estradiol; Estrogens; Female; Follicle Stimulating Hormone; Glucose; Growth Hormone; Hormones; Humans; Hypothalamo-Hypophyseal System; Hypothyroidism; Insulin; Liver Cirrhosis, Alcoholic; Liver Diseases; Luteinizing Hormone; Male; Melatonin; Neurotransmitter Agents; Parathyroid Hormone; Phosphorus; Pituitary Gland; Prolactin; Renin-Angiotensin System; Somatomedins; Testosterone; Thyroid Hormones; Thyrotropin-Releasing Hormone; Vasopressins; Vitamin D

Topics: Blood Transfusion; Central Venous Pressure; Cimetidine; Emergencies; Esophageal and Gastric Varices; Esophagoscopy; Esophagus; Fluid Therapy; Gastrointestinal Hemorrhage; Hemostasis, Surgical; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Prognosis; Sclerosing Solutions; Vasopressins; Vitamin K

In order to evaluate the activation of the sympathetic nervous and renin-angiotensin systems and antidiuretic hormone release in the setting of chronic liver disease, we studied 30 patients with cirrhosis who presented normal renal function. The cirrhotic patients were divided into two groups according to Child's score: 20 were Child A and 10 Child B. The control group consisted of 10 normal subjects. Blood samples were collected for determination of norepinephrine (NE), dopamine (DA), angiotensin I and II (AI and AII), and antidiuretic hormone (ADH), using the method of high-performance liquid chromatography (HPLC). No significant differences (p < 0.05) were found in the plasma levels of NE, DA, AI, and AII between the cirrhotic patients and the controls, although the absolute values observed in both groups of cirrhotics were clearly higher than in controls. The ADH levels were higher in Child B in comparison to Child A patients and controls, though this difference was not significant as well. Our results suggest a hormonal activation in cirrhotic patients, even in the early stages of hepatic disease (without ascites). We also noted an increase in ADH levels in Child B patients in relation to Child A and controls, although there was no difference in osmolality, suggesting a non-osmotic ADH release.

Topics: Adult; Angiotensin II; Chromatography, High Pressure Liquid; Chronic Disease; Dopamine; Hepatitis, Viral, Human; Humans; Liver Cirrhosis, Alcoholic; Liver Function Tests; Male; Middle Aged; Norepinephrine; Prognosis; Renin-Angiotensin System; Severity of Illness Index; Sympathetic Nervous System; Vasopressins

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephal

Topics: Acute Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Portacaval Shunt, Surgical; Radiography; Recurrence; Sclerosing Solutions; Vasopressins

Vasopressin is often used to treat variceal hemorrhage. However, its efficacy is uncertain, and its portal hemodynamic effects in this setting are unknown. Eleven patients with alcoholic liver disease and bleeding varices were given vasopressin (0.2 U/min for the first hour, then 0.4 U/min for 24 hours). Portal pressure was monitored using an indwelling hepatic vein balloon catheter. Seventeen patients with variceal bleeding who remained stable over 26 hours of initial treatment with crystalloid and blood products served as a comparison group. Vasopressin infusion (0.2 U/min) produced a significant decrease in wedged hepatic venous pressure, hepatic venous pressure gradient (wedged minus free hepatic venous pressure), and heart rate. Increases in the rate of infusion did not produce further decreases in the parameters measured, but the changes were sustained over the course of the infusion. Hemodynamics remained stable in the control group. Portal pressure did not increase when vasopressin was abruptly discontinued in the 3 patients in whom postinfusion measurements were made. Vasopressin retains its portal hypotensive effects in the setting of variceal hemorrhage. Tachyphylaxis does not develop over 26 hours, and a "rebound" increase in portal pressure probably does not occur when the infusion is discontinued.

Topics: Adult; Blood Pressure; Catheterization; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Hepatic Veins; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Vasopressins; Venous Pressure

Topics: Hepatorenal Syndrome; Humans; Kidney Diseases; Kidney Failure, Chronic; Liver Cirrhosis, Alcoholic; Ornipressin; Vasopressins

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8-ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p less than 0.01), urine volume (108 (29)%; p less than 0.05) and sodium excretion (168 (30)%; p less than 0.05). The hyperdynamic circulation of hepatic failure, as characterised by increased cardiac index and heart rate as well as decreased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p less than 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and renin-angiotensin-axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).

Topics: Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Norepinephrine; Ornipressin; Renin; Vasopressins

We evaluated a group of 21 cirrhotic patients with a standard 20 ml/kg water load. The patients segregated into three classes: class I (n = 6) had normal water load excretion, i.e. greater than 80% excretion over 5 h (mean 82.3 +/- 0.8%); class II (n = 8) had 20-80% excretion (mean 38.6 +/- 4.2%); and class III (n = 7) had less than 20% excretion (mean 12.9 +/- 1.2%). The patients in class III, who had profound impairment of water load excretion, were found to have a higher frequency of tense ascites, lower serum sodium concentrations, diuretic resistance, impairment of urinary sodium excretion, lower inulin and p-aminohippurate clearances, and elevations of plasma arginine vasopressin, aldosterone and norepinephrine concentrations. However, class III could only be distinguished from class II on the basis of excretion of a standard water load. No significant differences were found among the classes in liver function tests. We prospectively followed these patients. Classes I and II patients appear to have a good prognosis, if they avoid ethanol (4 of 5 patients still alive 42-56 months after evaluation). Class III patients have a poor prognosis independent of ethanol intake (all lived less than 5 months, except 1 patients who received a peritoneovenous shunt). Class I patients were found to tolerate continued ethanol consumption better than class II patients. Thus, an early intervention, such as the peritoneovenous shunt, may prolong survival among class III patients; however, this possibility needs to be evaluated in a larger prospective study.

Topics: Adult; Aldosterone; Blood Volume; Diuresis; Female; Humans; Kidney; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Norepinephrine; Renin; Sodium; Vasopressins

Plasma levels of atrial natriuretic peptide (ANP), aldosterone (PA), vasopressin (AVP), and the plasma renin activity (PRA) were examined in 15 vascularly decompensated patients suffering from liver cirrhosis, before and after administration of albumin and after a subsequent administration of furosemide. The initial ANP level was lower in 9 patients (group "A") and higher in 6 patients (group "B") than in healthy controls (Group "A": 19.5 +/- 3.0 fmol/ml; group "B": 36.7 +/- 3.9 fmol/ml; control: 25.8 +/- 2.4 fmol/ml). The initial PRA (4.4 +/- 1.0 ng AngI/ml/h) and AVP (8.5 +/- 1.5 pg/ml) activity in group "A" increased significantly compared to group "B" (PRA: 0.44 +/- 0.09; AVP: 4.1 +/- 0.5), indicating an intravascular volume depletion in group "A". Albumin infusion raised the urine and sodium excretion and the plasma concentration of ANP in group "A" but lowered in plasma levels of renin and vasopressin. The same parameters were not changed by albumin in group "B". Furosemide equally raised the urine flow rate and sodium excretion in both groups. Plasma ANP level depends on the intravascular volume, and the secondary change in its plasma concentration plays a considerable role in the retention of fluid and electrolytes in patients with cirrhosis. The increased intravascular volume in these patients depletes the fluid and electrolyte retention via the increase in ANP level.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Creatinine; Diuresis; Female; Furosemide; Hematocrit; Hormones; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Plasma Volume; Potassium; Renin; Serum Albumin; Sodium; Vasoconstriction; Vasopressins

Since 1963, a prospective evaluation of the emergency portacaval shunt procedure has been conducted in 264 unselected patients with cirrhosis and bleeding varices who underwent operation within 8 hours of admission to the emergency department. Of 153 patients who underwent operation 10 or more years ago, 45 (29 percent) have survived from 10 to 22 years and their current status is known. On admission, 40 percent of the long-term survivors had jaundice, 44 percent had ascites, 13 percent had encephalopathy (with an additional 9 percent with a history of encephalopathy), 29 percent had severe muscle wasting, and 82 percent had a hyperdynamic state. There were 9 Child's class A patients, 33 Child's class B patients, and 3 Child's class C patients. At operation, all patients had portal hypertension which was reduced by the shunt to a mean corrected free portal pressure of 18 mm saline solution. The emergency portacaval shunt procedure permanently controlled variceal bleeding. None of the patients bled again from varices, and the shunt remained patent throughout life in every patient. Encephalopathy did not affect 91 percent of the patients, but was a recurrent problem in 9 percent, usually related to the use of alcohol. Lifelong abstinence from alcohol occurred in 58 percent of the long-term survivors, but 11 percent resumed regular drinking and 31 percent consumed alcohol occasionally. Liver function declined compared with preoperative function in only 18 percent of the patients, almost always because of alcohol use. Ten years after operation, 73 percent of the patients were in excellent or good condition, and 68 percent were gainfully employed or engaged in full-time housework. Comparison of the 10 to 22 year survivors with our early group of 180 patients reported previously and our recent group of 84 patients showed no significant differences in preoperative or operative data. The single factor that appeared to influence long-term survival was resumption of regular use of alcohol. We conclude that the emergency portacaval shunt procedure, by preventing hemorrhage from varices, results in prolonged survival and an acceptable quality of life for a substantial number of patients with advanced alcoholic cirrhosis.

Topics: Adult; Aged; Alcohol Drinking; Coma; Emergencies; Esophageal and Gastric Varices; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Portacaval Shunt, Surgical; Postoperative Complications; Prospective Studies; Quality of Life; Time Factors; Vasopressins

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.

Topics: Azygos Vein; Blood Flow Velocity; Blood Pressure; Esophageal and Gastric Varices; Esophagoscopy; Female; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Portacaval Shunt, Surgical; Splenorenal Shunt, Surgical; Vasopressins

An infusion with Ornipressin (8-ornithin vasopressin) in a patient with decompensated alcoholic liver cirrhosis increased urinary volume from 30 ml/h to 500 ml/h, creatinine clearance from 24 to 65 ml/min, and fractional sodium excretion from 0.86% to 11.1%. Free water clearance decreased from -10.2 ml/h to -26.2 ml/h and noradrenaline plasma concentrations dropped from 2.04 to 1.37 ng/ml. After stopping Ornipressin infusion all values returned to initial concentrations. Possible effects are an increase of renal blood flow secondary to an increase in arterial blood pressure, possibly potentiated by the vasodilatory effect of the fall in noradrenaline and/or angiotensin concentration.

Topics: Adult; Female; Humans; Kidney; Liver Cirrhosis, Alcoholic; Ornipressin; Vasopressins

Continuous vasopressin infusion has been shown to control bleeding from oesophageal varices in patients with cirrhosis of the liver. The mortality, however, has not been changed. To investigate whether reduction of portal blood flow over a period of hours deteriorates the liver function, we measured the splanchnic blood flow and galactose and oxygen consumption in five cirrhotic patients during liver vein catheterization. Vasopressin was given as a continuous infusion of 0.2 units per min for three h. The splanchnic blood flow was reduced to 70% of control values and remained so throughout the infusion. After three h no impairment of the liver function was found. The wedged hepatic pressure (portal pressure) rose slightly, probably due to the increase of the central venous pressure reflecting impaired cardiac function. The reported beneficial effect of vasopressin on varix bleeding probably depends on the reduced portal flow per se.

Topics: Adult; Blood Pressure; Central Venous Pressure; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Infusions, Parenteral; Liver; Liver Circulation; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Splanchnic Circulation; Vasopressins

Experimental animal studies have suggested that certain vasodilators could minimize the adverse cardiovascular effects of vasopressin. We investigated the hemodynamic effects of isosorbide dinitrate, alone and in combination with vasopressin, in patients with liver cirrhosis. In 10 patients, isosorbide dinitrate, 5 mg sublingually, reduced portal pressure by 21% as assessed by the gradient between wedged and free hepatic venous pressure, but also decreased mean arterial pressure (MAP) by 20%, pulmonary artery wedge pressure (WP) by 50%, and oxygen delivery (DO2) by 13%. In 6 other patients, isosorbide dinitrate, 5 mg sublingually, combined with vasopressin, 0.4 U/min iv, reduced portal pressure by 37%, increased MAP by 13%, and mean pulmonary artery pressure (MPAP) by 70%, and decreased DO2 by 32%. Thus, isosorbide dinitrate reduces effectively portal hypertension in patients with liver cirrhosis, but also decreases DO2 to the tissues as a consequence of a fall in cardiac output due to decreased preload. At the dosage used in this study, isosorbide dinitrate does not prevent the adverse hemodynamic effects of vasopressin.

Topics: Adult; Aged; Blood Pressure; Cardiac Catheterization; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Portal; Isosorbide Dinitrate; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Oxygen; Pulmonary Wedge Pressure; Time Factors; Vasopressins

The fate of 359 consecutive alcoholic cirrhotic male patients with bleeding esophageal varices was determined through chart review and personal interview. Three historical periods (1966-70; 1971-75; 1976-80) were defined based on availability of different therapeutic modalities. Management of acutely bleeding varices by conservative, nonsurgical means, including embolization, was preferable to emergency surgery when considering 30-day mortality rates. Percutaneous transhepatic embolization of esophagogastric varices significantly improved the rate of control of hemorrhage and 30-day survival over previously employed nonsurgical methods. The combination of nonsurgical management of acute variceal hemorrhage followed by selective distal splenorenal shunting resulted in maximum salvage of the alcoholic cirrhotic patient.

Topics: Embolization, Therapeutic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis, Alcoholic; Male; Portasystemic Shunt, Surgical; Prognosis; Recurrence; Retrospective Studies; Splenorenal Shunt, Surgical; Vasopressins

In five hyponatremic, cirrhotic patients, demeclocycline hydrochloride was used to inhibit the hydroosmotic effect of vasopressin. In four, renal impairment developed during the 7 to 20 days of demeclocycline hydrochloride (900 to 1,200 mg/day) administration. In these four patients, creatinine clearance fell (72 to 20 mL/min, P less than .01) as BUN (12 to 47 mg/dl, P less than .02) and serum creatinine (0.9 to 4.2 mg/dl, P less than .01) levels rose. The azotemic effect of the drug could not be accounted for consistently by volume depletion secondary to its natriuretic effect. However, a close correlation between plasma demeclocycline levels and its azotemic effect was observed. We conclude that a nephrotoxic effect of demeclocycline severly limits its usefulness in treating hyponatremia in the cirrhotic patient.

Topics: Adult; Creatinine; Demeclocycline; Glomerular Filtration Rate; Humans; Hyponatremia; Kidney; Kidney Diseases; Liver Cirrhosis, Alcoholic; Male; Natriuresis; Vasopressins

Topics: Demeclocycline; Humans; Kidney Failure, Chronic; Liver Cirrhosis, Alcoholic; Radioimmunoassay; Vasopressins