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• W2015535570 abstract "Portal hypertension results from increases in portal flow and portal vascular resistance. Factors increasing portal blood flow are predominantly humoral. Resistance to portal flow has a fixed component due to distortion of the vasculature by cirrhotic nodules and a variable component that is related to vasoactive substances. Varices result from an increase in portal pressure. Factors predicting the risk of variceal bleeding include continued alcohol use, poor liver function, large varices, and red wale markings on varices at endoscopy. Octreotide is probably the drug of choice for pharmacologic management of bleeding esophageal varices. Propranolol has an established role in the prevention of variceal hemorrhage, andvariceal band ligation may be the preferred endoscopic technique. Transjugular intrahepatic portosystemic shunts have emerged as an important treatment for patients in whom pharmacologic and endoscopic therapies have failed and are an effective bridge to liver transplantation. Portal hypertension results from increases in portal flow and portal vascular resistance. Factors increasing portal blood flow are predominantly humoral. Resistance to portal flow has a fixed component due to distortion of the vasculature by cirrhotic nodules and a variable component that is related to vasoactive substances. Varices result from an increase in portal pressure. Factors predicting the risk of variceal bleeding include continued alcohol use, poor liver function, large varices, and red wale markings on varices at endoscopy. Octreotide is probably the drug of choice for pharmacologic management of bleeding esophageal varices. Propranolol has an established role in the prevention of variceal hemorrhage, andvariceal band ligation may be the preferred endoscopic technique. Transjugular intrahepatic portosystemic shunts have emerged as an important treatment for patients in whom pharmacologic and endoscopic therapies have failed and are an effective bridge to liver transplantation. The three major and potentially fatal complications of cirrhosis of the liver-namely, variceal hemorrhage, ascites, and encephalopathy—are related to portal hypertension, which is defined as a hepatic venous pressure gradient (HVPG) of greater than 6 mm Hg. The elevation of portal pressure in cirrhosis results from increased resistance to flow of portal venous blood at the presinusoidal, sinusoidal, or postsinusoidal level. With increasing portal pressure, a portosystemic collateral circulation develops, the consequences of which include variceal hemorrhage, ascites, and portosystemic encephalopathy. Herein we review the pathophysiology of portal hypertension in patients with cirrhosis of the liver and discuss, in particular, the management of the major consequence of portal hypertension—variceal hemorrhage. As in all vascular systems, pressure within the portal system is a product of flow and resistance; thus, portal pressure equals portal flow × resistance to portal flow. Increases in portal flow, resistance, or both result in increased portal venous pressure.1Bosch J Pizcueta P Feu F Fernandez M Garcia-Pagan JC Patho-physiology of portal hypertension.Gastroenterol Clin North Am. 1992 Mar; 21: 1-14PubMed Google Scholar Cirrhosis of the liver is characterized by systemic and splanchnic vasodilatation. This increased state causes a hyperdynamic circulation with a high cardiac output, tachycardia, and relative hypotension in the systemic circulation and increased mesenteric and portal blood flow in the splanchnic circulation. This state of vasodilatation has been recognized for more than 40 years,2Abelmann WH Hyperdynamic circulation in cirrhosis: a historical perspective [editorial].Hepatology. 1994; 20: 1356-1358Crossref PubMed Scopus (88) Google Scholar The factors believed to be responsible for the vasodilatation include nitric oxide.3Bomzon A Blendis LM The nitric oxide hypothesis and the hyperdynamic circulation in cirrhosis.Hepatology. 1994; 20: 1343-1350Crossref PubMed Scopus (164) Google Scholar, 4Groszmann RJ Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences [editorial].Hepatology. 1994; 20: 1359-1363Crossref PubMed Scopus (333) Google Scholar In contrast, resistance to portal flow is related both to mechanical factors distorting the liver microcirculation and to vasoactive substances modulating flow through the liver. Systemic vasodilatation has been demonstrated in animal models of both prehepatic portal hypertension (portal vein-ligated rats) and intrahepatic portal hypertension (rats with cirrhosis of the liver induced by carbon tetrachloride). In these animals, there is hyporesponsiveness of the mesenteric arterial bed to vasoconstrictors such as norepinephrine7Kiel JW Pitts V Benoit JN Granger DN Shepherd AP Reduced vascular sensitivity to norepinephrine in portal-hypertensive rats.Am J Physiol. 1985; 248: G192-G195PubMed Google Scholar and endothelin,8Hartleb M Moreau R Cailmail S Gaudin C Lebrec D Vascular hyporesponsiveness to endothelin 1 in rats with cirrhosis.Gastroenterology. 1994; 107: 1085-1093Abstract PubMed Google Scholar which results in vasodilatation and thus increased mesenteric and portal blood flow. This decreased responsiveness to vasoconstrictors seems to be due to the presence of vasodilatory substances, including prostaglandins,9Bruix J Bosch J Kravetz D Mastai R Rodes J Effects of prosta-glandin inhibition on systemic and hepatic hemodynamics in patients with cirrhosis of the liver.Gastroenterology. 1985; 88: 430-435PubMed Google Scholar glucagon,10Kravetz D Arderiu M Bosch J Fuster J Visa J Casamitjana R et al.Hyperglucagonemia and hyperkinetic circulation after portocaval shunt in the rat.Am J Physiol. 1987; 252: G257-G261PubMed Google Scholar and nitric oxide.5Sieber CC Lopez-Talavera JC Groszmann RJ Role of nitric oxide in the in vitro splanchnic vascular hyporeactivity in ascitic cirrhotic rats.Gastroenterology. 1993; 104: 1750-1754Abstract PubMed Google Scholar, 6Sieber CC Groszmann RJ In vitro hyporeactivity to methoxamine in portal hypertensive rats: reversal by nitric oxide blockade.Am J Physiol. 1992; 262: G996-G1001PubMed Google Scholar Glucagon, the most studied of these substances, accounts for only 30 to 40% of the splanchnic vasodilatation of chronic portal hypertension.10Kravetz D Arderiu M Bosch J Fuster J Visa J Casamitjana R et al.Hyperglucagonemia and hyperkinetic circulation after portocaval shunt in the rat.Am J Physiol. 1987; 252: G257-G261PubMed Google Scholar, 11PakJM, LeeSS Glucagon in portal hypertension.JHepatol. 1994; 20: 825-832Abstract Full Text PDF Scopus (37) Google Scholar Recent evidence indicates that arterial hypotension in cirrhotic rats with ascites may be induced by nitric oxide because nitric oxide inhibitors correct arterial hypotension.12Claria J Jimenez W Ros J Asbert M Castro A Arroyo V et al.Pathogenesis of arterial hypotension in cirrhotic rats with ascites: role of endogenous nitric oxide.Hepatology. 1992; 15: 343-349Crossref PubMed Scopus (190) Google Scholar Tumor necrosis factor (TNF-α) has also been implicated in the vasodilatation of prehepatic portal hypertension. In an animal model of portal hypertension produced by ligation of the portal vein, anti-TNF-α increased arterial pressure, heart rate, and systemic vascular resistance.13Lopez-Talavera JC Merrill WW Groszmann RJ Tumor necrosis factor a: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats.Gastroenterology. 1995; 108: 761-767Abstract Full Text PDF PubMed Scopus (158) Google Scholar The hyperdynamic circulation was almost completely abolished by inhibition of TNF-α. Thus, current evidence points to glucagon, prostaglandins, nitric oxide, and, probably, TNF-α as the candidate substances involved in the vasodilatation of cirrhosis of the liver (Table 1). These vasodilator substances are probably splanchnic in origin and accumulate in the systemic circulation because of either increased production or decreased metabolism by the diseased liver. With progression of liver disease, portosystemic shunting occurs, which further decreases hepatic uptake and increases levels of vasodilator substances in the systemic circulation. Hence, vasodilators may be important not only in the initiation of portal hypertension but also in its propagation.Table 1Pathophysiology of Portal Hypertension Factors increasing portal blood flow Nitric oxideGlucagonProstaglandinsTumor necrosis factor αFactors increasing resistance to portal blood flow Fixed component FibrosisVascular distortion by nodulesVariable component Endothelin Open table in a new tab The major site of resistance within the portal circulation is at the level of the sinusoids. Resistance to blood flow has two components—a fixed component, which is related to distortion of the vessels by cirrhotic nodules, and a variable component, which is related to vasoactive substances (Table 1). The reversible factors that mediate vascular resistance have not been as well studied as the factors that increase portal blood flow. Several years ago, Bhathal and Grossman14Bhathal PS Grossman HJ Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilators.J Hepatol. 1985; 1: 325-337Abstract Full Text PDF PubMed Scopus (296) Google Scholar demonstrated that resistance to blood flow within the liver could be modified by vasoactive substances. Our studies in bile duct-ligated rats suggest that the reversible component of intrahepatic resistance may be modulated by endothelins and that nitric oxide has less of a role. Endothelins are a family of vasoactive peptides, of which endothelin-1 (ET-1) is a potent constrictor of vascular smooth muscle. ET-1 is increased in the peripheral blood of patients with chronic liver disease and ascites15Asbert M Gines A Gines P Jimenez W Claria J Salo J et al.Circulating levels of endothelin in cirrhosis.Gastroenterology. 1993; 104: 1485-1491PubMed Google Scholar and in those with the hepatorenal syndrome.16Moore K Wendon J Frazer M Karani J Williams R Badr K Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome.N Engl J Med. 1992; 327: 1774-1778Crossref PubMed Scopus (345) Google Scholar ET-1 has been localized to the endothelial cells of the hepatic sinusoids, portal vein, and central vein.17Gondo K Ueno T Sakamoto M Sakisaka S Sata M Tanikawa K The endothelin-1 binding site in rat liver tissue: light- and electron-microscopic autoradiographic studies.Gastroenterology. 1993; 104: 1745-1749PubMed Google Scholar In a rat model, an endothelin blocker decreased intrahepatic resistance toward normal, whereas in control animals, no change was noted.18Kamath PS Grabau C Ward L Tyce GM Miller VM Rorie DK Increased intrahepatic resistance in portal hypertension is mediated by endothelin [abstract].Hepatology. 1993; 18: 282ACrossref Google Scholar This finding suggests that endothelin is at least partly responsible for the increased resistance to portal blood flow in cirrhosis of the liver. The mechanisms underlying this phenomenon must be explored further. Portal pressure can be measured in several ways, the most common of which is measurement of wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) with use of a femoral vein approach. The procedure aims at measuring pressure within the hepatic sinusoids. The most reproducible method for measuring WHVP is by using a balloon catheter. When the catheter is in the wedged position, the pressure tracing is stable, with no reflux of contrast into the portal vein; withdrawal of the catheter results in a precipitous decrease in pressure.19Lebrec D Methods to evaluate portal hypertension.Gastroenterol Clin North Am. 1992 Mar; 21: 41-59PubMed Google Scholar FHVP is measured at the junction of the hepatic vein and the inferior vena cava. WHVP represents hepatic sinusoidal pressure, somewhat akin to pulmonary wedge pressure representing left atrial pressure. The FHVP is the reference for measurement of portal pressure, similar to right atrial pressure being the reference for systemic venous pressure. The difference between WHVP and FHVP is the HVPG, and in normal subjects, it is less than 5 mm Hg. Portal hypertension is diagnosed when the HVPG is greater than 6 mm Hg. The risk of variceal bleeding increases when the HVPG is higher than 12 mm Hg and is insignificant when the HVPG is lower than this level.20Groszmann RJ Bosch J Grace ND Conn HO Garcia-Tsao G Navasa M et al.Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage.Gastroenterology. 1990; 99: 1401-1407Abstract PubMed Google Scholar WHVP best represents sinusoidal pressure in alcoholic liver disease and posthepatic cirrhosis. In cholestatic liver diseases like primary biliary cirrhosis, WHVP is somewhat less than the portal pressure, an indication of a presinusoidal component of portal resistance. Similarly, WHVP underrepresents sinusoidal pressure in venoocclusive disease and is normal in portal venous thrombosis causing portal hypertension. Normal liver hemodynamic values are listed in Table 2.Table 2Normal Liver Hemodynamic ValuesModified from Kamath PS. Haemodynamics of the liver and its alteration in disease. Trop Gastroenterol 1983;4:79-99.MeasurementNormal valuePressures (mm Hg) Hepatic artery100 Portal vein5-8 Inferior vena cava1-2 Wedged hepatic venous pressure (WHVP)5-8 Free hepatic venous pressure (FHVP)1-2 Hepatic venous pressure gradient (WHVP-FHVP)<6Flow rates and volumes (mL/min) Estimated hepatic blood flow1,500 Hepatic artery blood flow350 Portal blood flow1,150 Hepatic blood volume (mL)500Oxygen supply to the liver (%) Through portal vein72 Through hepatic artery28 Open table in a new tab Two other measurements deserve comment—namely, esophageal variceal pressure and azygos blood flow. The risk of a variceal hemorrhage is related to pressure within the varix. Attempts have been made to measure pressure within the varix at endoscopy by using either a needle or a balloon; the balloon technique is safer.21Gertsch P Fischer G Kleber G Wheatley AM Geigenberger G Sauerbruch T Manometry of esophageal varices: comparison of an endoscopic balloon technique with needle puncture.Gastroenterol-ogy. 1993; 105: 1159-1166Google Scholar Measurement of variceal pressure has not been studied extensively enough to determine the pressure level below which variceal hemorrhage is not likely to occur. Azygos blood flow (Fig. 1) is measured by a thermal dilution technique. Most of the portosystemic collateral blood flow is returned to the superior vena cava through the azygos vein, and thus azygos blood flow is a good representation of the amount of collateral circulation. In normal subjects, azygos blood flow is less than 200 mL/min, whereas in patients with portal hypertension, it is increased to 220 to 1,600 mL/min.22Bosch J Groszmann RJ Measurement of azygos venous blood flow by a continuous thermal dilution technique: an index of blood flow through gastroesophageal collaterals in cirrhosis.Hepatology. 1984; 4: 424-429Crossref PubMed Scopus (188) Google Scholar Measurement of azygos blood flow is not helpful in the routine clinical management of variceal hemorrhage, but it is a useful research tool. Variceal hemorrhage, ascites, and portosystemic encephalopathy are the major consequences of portal hypertension. This discussion focuses on the pathogenesis of variceal formation. Normal resistance to portal blood flow is at the level of the hepatic sinusoid. The classification of portal hypertension based on the site of obstruction is depicted in Figure 2. Portosystemic collateral vessels have a high resistance, and thus splanchnic blood normally flows almost entirely into the portal vein. With increased blood flow to the liver due to splanchnic vasodilatation, resistance to blood flow within the portal venous system increases, an outcome that results in the opening of portosystemic collateral channels. Splanchnic blood can now flow either into the portal vein or through the collateral veins. With increasing resistance to blood flow in the portal circulation due to both humoral and mechanical factors, portal flow decreases, and collateral blood flow increases. The collaterals are formed at sites where systemic veins are close to veins that normally drain into the portal system. These collaterals manifest as varicosities at the lower end of the esophagus between the left gastric vein and the azygos vein; in the rectum, between the inferior hemorrhoidal plexus and the middle and superior hemorrhoidal plexus; around the umbilicus; and around the ovaries. Varices also develop at other sites including the small bowel, cecum, and stomal sites, and these are referred to as ectopic varices. The risk of bleeding from varices is minimal when the HVPG is lower than 12 mm Hg. A recent study showed that portal pressure has a circadian variation, in which HVPG is highest shortly after midnight, decreased significantly after 9 AM, and lowest at 7 PM.23Garcia-Pagan JC Feu F Castells A Luca A Hermida RC Rivera F et al.Circadian variations of portal pressure and variceal hemorrhage in patients with cirrhosis.Hepatology. 1994; 19: 595-601Crossref PubMed Scopus (64) Google Scholar This circadian variation might explain why variceal hemorrhage occurs more often during the early hours that at any other time during the day.23Garcia-Pagan JC Feu F Castells A Luca A Hermida RC Rivera F et al.Circadian variations of portal pressure and variceal hemorrhage in patients with cirrhosis.Hepatology. 1994; 19: 595-601Crossref PubMed Scopus (64) Google Scholar When esophageal varices are noted, portal pressure is invariably high, although no clear correlation exists between the development of varices and the degree of portal hypertension.19Lebrec D Methods to evaluate portal hypertension.Gastroenterol Clin North Am. 1992 Mar; 21: 41-59PubMed Google Scholar The most common method of detecting varices is by endoscopy. Transcutaneous ultrasonography demonstrates varices in a large percentage of patients, but its major role is in determining patency of the portal venous system.24Vilgrain V Lebrec D Menu Y Scherrer A Nahum H Comparison between ultrasonographic signs and the degree of portal hypertension in patients with cirrhosis.Gastrointest Radiol. 1990; 15: 218-222Crossref PubMed Scopus (62) Google Scholar Computed tomography and magnetic resonance angiography can also detect varices. Although no studies have compared these radiologic techniques to endoscopy, they are generally considered inferior for the detection of varices. Angiography is useful for delineation of the portal venous system. The usual technique used for this purpose is venous phase celiac artery angiography. Angiography can also detect fistulas between the arterial system and the portal venous system. The fistula can be between the splenic artery and the splenic vein, but it is usually between a branch of the hepatic artery and the portal vein and may be a consequence of a liver biopsy. Angiography demonstrates not only the venous collaterals but also the site of the fistula. Contrast angiography is essential before a portosystemic shunt surgical procedure is planned because Doppler ultrasonography and magnetic resonance imaging may not always reliably detect thrombosis of the portal venous system. Variceal hemorrhage is associated with high morbidity and mortality. Furthermore, the management of gastrointestinal bleeding due to portal hypertension is associated with substantial economic costs. About 10% of all patients with acute upper gastrointestinal bleeding admitted to hospitals in the United States (an estimated 40,000 patients) have one or more episodes of gastrointestinal bleeding per year due to portal hypertension. The estimated annual cost of treatment of bleeding and bleeding-related complications is $30,000 per patient;25Cello JP Grendell JH Crass RA Weber TE Trunkey DD Endoscopic sclerotherapy versus portacaval shunt in patients with severe cirrhosis and acute variceal hemorrhage: long-term follow-up.NEnglJMed. 1987; 316: 11-15Crossref Scopus (222) Google Scholar thus, gastrointestinal bleeding due to portal hypertension accounts for approximately $1.2 billion in health-care expenditures. In populations of patients with cirrhosis of the liver, the prevalence of esophageal varices is 25 to 70%, depending primarily on the prevalence of end-stage liver disease. Of patients with cirrhosis of the liver, 10 to 15% will have development of varices each year. Esophageal varices and congestive gastropathy will eventually develop in most patients with alcoholic cirrhosis.26Burroughs AK McCormick PA Natural history and prognosis of variceal bleeding.Baillieres Clin Gastroenterol. 1992; 6: 437-450Abstract Full Text PDF PubMed Scopus (56) Google Scholar In a subgroup of patients, however, esophageal varices may stabilize or even regress. This phenomenon is most likely to occur in patients with alcoholic cirrhosis who discontinue drinking, but cessation of alcohol abuse is not a guarantee of variceal regression. One-third of patients with cirrhosis who have documented varices experience an episode of variceal hemorrhage. The incidence of bleeding is related to the severity of the underlying disease, and most bleeding episodes occur within the first 2 years after varices have been discovered.26Burroughs AK McCormick PA Natural history and prognosis of variceal bleeding.Baillieres Clin Gastroenterol. 1992; 6: 437-450Abstract Full Text PDF PubMed Scopus (56) Google Scholar Currently, even with optimal management, 25 to 50% of patients die after their first hemorrhage. During the first 6 weeks after the initial bleeding episode, the risk of rebleeding is increased; the highest risk is during the first few days. The mean mortality associated with subsequent bleeding is about 25% because most high-risk patients die after the first hemorrhage; however, the mortality rate based on the modified Child classification remains the same: class A, 5%; class B, 25% or less; and class C, 50% or more.26Burroughs AK McCormick PA Natural history and prognosis of variceal bleeding.Baillieres Clin Gastroenterol. 1992; 6: 437-450Abstract Full Text PDF PubMed Scopus (56) Google Scholar The risk of death becomes virtually constant about 6 weeks after hemorrhage. Therefore, unless effective therapeutic measures are taken during this high-risk period to prevent rebleeding, survival is unlikely to be affected because all therapeutic measures, except liver transplantation, have no beneficial effect on liver function. Because only a third of patients with varices experience bleeding episodes, the ability to identify those at highest risk of bleeding is of great clinical utility. Factors that seem to increase the risk of both initial and subsequent bleeding include continued alcohol abuse, level of liver decompensation based on the Child classification, large varices, red wale markings on varices at endoscopy, presence of gastric varices,27Kleber G Sauerbruch T Fischer G Geigenberger G Paumgartner G Reduction of transmural oesophageal variceal pressure by metoclopramide.J Hepatol. 1991; 12: 362-366Abstract Full Text PDF PubMed Scopus (27) Google Scholar changes in the velocity or reversal of portal flow as evaluated by Doppler echocardiography,28Gaiani S Bolondi L Li Bassi S Zironi G Siringo S Barbara L Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis: clinical and endoscopic correlation in 228 patients.Gastroenterology. 1991; 100: 160-167PubMed Google Scholar and persistence or development of ascites.29Conn HO Lindenmuth WW May CJ Ramsby GR Prophylactic portacaval anastomosis.Medicine. 1972; 51: 27-40Crossref PubMed Scopus (186) Google Scholar Of these variables, the factors shown to predict independently the risk of first variceal hemorrhage are Child class C, large varices, and red wale markings on the varices.30North Italian Endoscopic Club for the Study and Treatment of Esoph-ageal Varices Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices: a prospective multicenterstudy.NEnglJMed. 1988; 319: 983-989Crossref Scopus (1070) Google Scholar The modalities available to treat variceal hemorrhage are pharmacologic agents, endoscopic therapy, balloon tamponade, transjugular intrahepatic portosystemic shunts (TIPS), surgical intervention, and liver transplantation. Liver transplantation, however, will not be discussed in this review. most commonly used pharmacologic agents for the control of acute variceal hemorrhage are vasopressin, terlipressin, somatostatin, and octreotide; β-adrenergic blocking agents are used in the prevention of bleeding. Vasopressin.—Until recently, vasopressin was the drug most widely used to control acute variceal hemorrhage. Vasopressin causes splanchnic arteriolar constriction, which results in reduced portal venous inflow and a consequent decrease in portal venous pressure of 20 to 30% as measured by the WHVP gradient.31Bosch J Navasa M Garcia-Pagan JC DeLacy AM Rodes J Portal hypertension.Med Clin North Am. 1989 Jul; 73: 931-953PubMed Google Scholar It also decreases azygos blood flow by 25% and reduces intravariceal pressure.32Bosch J Bordas JM Mastai R Kravetz D Navasa M Chesta J et al.Effects of vasopressin on the intravariceal pressure in patients with cirrhosis: comparison with the effects on portal pressure.Hepatology. 1988; 8: 861-865Crossref PubMed Scopus (72) Google Scholar Because vasopressin has a short half-life, it must be given by continuous intravenous infusion. It may be administered as a 20-U bolus intravenously over 20 minutes, followed by a continuous infusion of 0.4 U/min; however, it is frequently administered as a continuous infusion without a bolus dose. Unfortunately, vasopressin causes a high rate of cardiac complications in elderly persons, including coronary vasoconstriction, reduced cardiac output, myocardial ischemia and infarction, and potentially fatal arrhythmias, and thus treatment may need to be discontinued. Vasopressin can cause an increase in blood pressure with reflex bradycardia in the setting of active bleeding, which may lead to a false sense of security because these factors indicate improved hemodynamic stability. Furthermore, vasopressin acts on the kidney to prevent excretion of free water, which results in fluid overload, hyponatremia, and increasing ascites. Vascular complications related to generalized systemic vasoconstriction include mesenteric infarction, limb ischemia, and cerebrovascular accidents. In 25 to 30% of patients, use of vasopressin must be discontinued because of adverse effects, and the mortality related to vasopressin administration is approximately 5%.33Westaby D The management of active variceal bleeding.J Hepatol. 1993; 17: S34-S37Abstract Full Text PDF Scopus (9) Google Scholar Overall, vasopressin has proved to be no better than placebo relative to decreasing the need for emergency surgical treatment or transfusion requirement or in reducing mortality. Thus, enthusiasm for its use in the management of an acute gastrointestinal bleeding episode associated with portal hypertension is declining. Nitroglycerin.—Nitroglycerin has been used in combination with vasopressin in an attempt to attenuate the adverse cardiovascular side effects of vasopressin. Transdermally administered nitroglycerin increases the efficacy of vasopressin in controlling variceal hemorrhage but does not decrease cardiovascular complications. The optimal route of administration of nitroglycerin is intravenous with an initial dose of 40 μg/min, and incremental doses are given if the systolic blood pressure is higher than 100 mm Hg. Although 400 μg/min is considered the upper limit, we have found that it is impossible to increase the dose higher than 100 µg/min without causing profound hypotension. The combination of vasopressin and nitroglycerin results in a reduced rate of cardiac complications and more frequent control of bleeding in comparison with vasopressin alone.34Bosch J Groszmann RJ Garcia-Pagan JC Teres J Garcia-Tsao G Navasa M et al.Association of transdermal nitroglycerin to vasopressin infusion in the treatment of variceal hemorrhage: a placebo-controlled clinical trial.Hepatology. 1989; 10: 962-968Crossref PubMed Scopus (94) Google Scholar Terlipressin.—Terlipressin (glypressin), a synthetic triglycyl-lysine derivative of vasopressin, is slowly cleaved in vivo to release vasopressin. It has a longer duration of action and can be administered as a bolus intravenous injection of 1 to 2 mg every 4 to 6 hours. In controlled trials, terlipressin has been shown to control bleeding much more effectively than vasopressin, and transfusion requirements are lower. Ongoing trials of terlipressin in combination with intravenous nitroglycerin therapy show encouraging preliminary results.35Lin HC Tsai YT Lee FY Chang TT Wang SS Lay CS et al.Systemic and portal haemodynamic changes following triglycllysine vasopressin plus nitroglycerin administration in patients with hepatitis B-related cirrhosis.J Hepatol. 1990; 10: 370-374Abstract Full Text PDF PubMed Scopus (28) Google Scholar Somatostatin.—Somatostatin, a 14-amino acid peptide, decreases splanchnic blood flow by a direct and selective action on mesenteric vascular smooth muscle as well as by reducing glucagon levels. It has a substantial advantage over vasopressin in that it does not produce systemic vasoconstriction. The short half-life of somatostatin (1 to 2 minutes) necessitates administration as an initial intravenous bolus of 250 μg, followed by a continuou" @default.
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• W2015535570 title "Pathophysiology and Treatment of Variceal Hemorrhage" @default.
• W2015535570 cites W125353679 @default.
• W2015535570 cites W1490171983 @default.
• W2015535570 cites W1490907837 @default.
• W2015535570 cites W1502333213 @default.
• W2015535570 cites W155891895 @default.
• W2015535570 cites W1575024810 @default.
• W2015535570 cites W1666404037 @default.
• W2015535570 cites W1798628354 @default.
• W2015535570 cites W1857298692 @default.
• W2015535570 cites W1894472884 @default.
• W2015535570 cites W1951872191 @default.
• W2015535570 cites W1967467373 @default.
• W2015535570 cites W1985939268 @default.
• W2015535570 cites W1992923345 @default.
• W2015535570 cites W1995198271 @default.
• W2015535570 cites W2006306512 @default.
• W2015535570 cites W2007677328 @default.
• W2015535570 cites W2013388826 @default.
• W2015535570 cites W2017924020 @default.
• W2015535570 cites W2018234166 @default.
• W2015535570 cites W2018339974 @default.
• W2015535570 cites W2021835419 @default.
• W2015535570 cites W2021937089 @default.
• W2015535570 cites W2023358953 @default.
• W2015535570 cites W2023491041 @default.
• W2015535570 cites W2024984749 @default.
• W2015535570 cites W2026776095 @default.
• W2015535570 cites W2028647951 @default.
• W2015535570 cites W2038555708 @default.
• W2015535570 cites W2041553454 @default.
• W2015535570 cites W2053569357 @default.
• W2015535570 cites W2059612953 @default.
• W2015535570 cites W2068581673 @default.
• W2015535570 cites W2070381187 @default.
• W2015535570 cites W2071142226 @default.
• W2015535570 cites W2080099185 @default.
• W2015535570 cites W2081843465 @default.
• W2015535570 cites W2092223809 @default.
• W2015535570 cites W2093495401 @default.
• W2015535570 cites W2120274756 @default.
• W2015535570 cites W2121848682 @default.
• W2015535570 cites W2135441431 @default.
• W2015535570 cites W2139021344 @default.
• W2015535570 cites W2144241236 @default.
• W2015535570 cites W2154593257 @default.
• W2015535570 cites W2162113187 @default.
• W2015535570 cites W2166771019 @default.
• W2015535570 cites W2314215304 @default.
• W2015535570 cites W2330258550 @default.
• W2015535570 cites W2339736887 @default.
• W2015535570 cites W2406529504 @default.
• W2015535570 cites W2415183088 @default.
• W2015535570 cites W2432477477 @default.
• W2015535570 cites W2436296430 @default.
• W2015535570 cites W2795638792 @default.
• W2015535570 cites W4246914844 @default.
• W2015535570 cites W4300112778 @default.
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