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A COMMONSENSE APPROACH TO VARICEAL BLEEDING
PORTAL HYPERTENSION
1089-3261/97 $0.00
+ .20
A COMMONSENSE APPROACH TO VARICEAL BLEEDING Douglas R. LaBrecque, MD, FACP
INTRODUCTION Hematemesis due to acute variceal bleeding is the most dramatic and frightening consequence of portal hypertension, and with good reason. As noted in the preceeding articles, up to fifty percent of patients do not leave the hospital alive following their initial variceal bleed. As our understanding of the causes of acute variceal bleeding has increased, the esophageal varix has come to be viewed more and more as a dormant volcano, needing only an appropriate rise in pressure to breach its already stretched and progressively thinning endothelial covering. In the face of such potentially dire consequences, great efforts have been expended to prevent the first bleed, to treat the first bleed more successfully and to prevent future bleeds. Details of the various approaches currently available and those still under investigation, the rationale behind the different therapeutic choices, and extensive bibliographies supporting these choices are contained in the preceeding articles. From a careful reading of these articles one can develop a reasonable, rational, cost effective approach to variceal bleeding in the patient with cirrhosis and portal hypertension. However, the best approach varies depending on the technology and expertise available at a particular location. Ideally, the patient with an acute variceal bleed will be taken to a medical center with excellent emergency facilities and an intensive care unit experienced in the care of acute variceal bleeders where he or she From the Liver Service, University of Iowa Hospitals and Clinics; and the Veterans Administration Medical Center, Iowa City, Iowa
CLINICS IN LIVER DISEASE
-
-
VOLUME 1 NUMBER 1 MAY 1997
121
122
LaBRECQUE
can be rapidly evaluated and resuscitated by a team comprised of a hepatologist, endoscopist, therapeutic radiologist and hepatobiliary/ transplant surgeon. However, many are first taken to a smaller hospital which may lack one or all of the above. This article attempts to summarize a reasonable approach to the patient at the different points of presentation: (1)before the initial bleed; (2) at the time of an acute bleed; and (3) following an acute bleed. Detailed discussions of the procedures recommended and extensive literature supporting the recommendations can be found in the preceeding articles and are not repeated here. PREVENTING THE FIRST BLEED
Varices rarely bleed until the portal pressure equals or exceeds 12 mmHg (see articles by Gupta et a1 and Boyer). This level of portal pressure is not usually reached in the absence of cirrhosis, although there are important exceptions (see article by Lebrec et al). Prophylaxis to prevent variceal bleeding starts with the recognition that the patient has cirrhosis and documentation of the presence of portal hypertension. The importance of recognizing physical findings which suggest portal hypertension or advanced liver disease, historical indications of portal hypertension, and more subtle signs of variceal bleeding, cannot be overemphasized. Minor hematochezia or iron deficiency anemia rather than dramatic, life threatening hematemesis may be the only indication of variceal bleeding. One must first recognize the presence of portal hypertension before one can treat it prophylactically. The patient with chronic liver disease as evidenced by 6 months of elevated transaminases or physical evidence of chronicity (splenomegaly, prominent abdominal collaterals, ascites, hepatic encephalopathy) should have an abdominal ultrasound performed with doppler examination to rule out hepatic, portal or splenic vein obstruction, look for the presence of collaterals or a patent umbilical vein, and rule out hepatic or other intraabdominal masses. This can be complemented by CT examination, which will provide a clearer anatomic evaluation of the liver and is better able to visualize the pancreas and splenic vasculature which are often obscured by stomach gas. A liver biopsy should be performed to document the presence of cirrhosis and attempt to determine the etiology of the underlying liver disease. Appropriate serologic tests should also be performed to rule out viral, autoimmune, inherited, and metabolic causes. Pharmaciologic therapy is clearly beneficial in preventing the first esophageal variceal bleed in patients with Child’s Class A or B cirrhosis. Its value in patients who are Child’s class C is less clear (See article by Grace and Bhattacharya). A portal pressure above 12 mm Hg is probably the best indicator of potential for a variceal bleed but is not routinely available at most centers. Based on the expectation that approximately 50% of cirrhotics will have esophageal varices, the 1996 AASLD Conference on Portal Hypertension recommended routine endoscopy in cir-
A COMMONSENSE APPROACH TO VARlCEAL BLEEDING
123
rhotics to determine if varices were present. Several findings at endoscopy have been associated with a high risk of variceal hemorrage and are a reasonable substitute for measurement of the portal pressure. These include the presence of large varices, red wale markings and cherry red spots (see article by Boyer). In the presence of such findings in a patient with Child’s Class A or B cirrhosis, the patient should be started on a noncardiac selective beta blocker, typically 40 mg twice daily of propranolol or nadalol 40 mg per day. The dose is adjusted upwards to reduce the resting heart rate by 25 percent or to a rate of 55 to 60 beats per minute. Such a regimen can be expected to reduce the risk of bleeding and increase survival as well.7The cost effectiveness of prophylactic therapy in patients with small varices and none of the risk factors lised above is less clear, although many clinicians will choose to treat any patient with varices, regardless of size. A recent study has documented that propranolol is the only cost effective form of prophylactic therapy to prevent the initial variceal bleed in cirrhotics regardless of the risk of bleeding. Propranolol also increased the quality-adjusted life expectancy. Sclerotherapy was much less cost effective and did not increase life expectancy. And while shunt surgery was quite effective in decreasing the risk of bleeding, it also decreased overall life expectancy due to increased deaths from liver failure and hepatic encephalopathy, and was not cost effective.’O (A more detailed discussion of the overall cost-effectiveness of various strategies of treating the problem of variceal bleeding can be found in the article by Gralnek and Jensen.) When available, portal pressure should be measured prior to treatment and again 2 to 3 months later to document a drop to below 12 mmHg or at least 20% below the pretreatment value. In most centers, however, this will not be practical and the heart rate adjustment referred to above is an acceptable surrogate parameter with which to judge the effectiveness of therapy. Two recent abstracts1,l2 suggest that Doppler ultrasound assessment of portal venous blood flow may also serve as a reliable surrogate marker of a drop in portal pressure. Unfortunately, up to a quarter of patients may not tolerate longterm therapy with propranolol due to underlying cardiac or pulmonary disease, asthma, insulin dependent diabetes or other medical contraindications. For such patients, nadolol may be better tolerated. Another option is the use of long-acting nitrates. Although less well studied, isosorbide-5 mononitrate was found to be as effective as propranolol in one controlled trial.’
MANAGING THE FIRST VARICEAL BLEED
Historically, up to 50% of patients have died at the time of their first variceal bleed and variceal bleeding is the cause of death in about one third of all cirrhotics. Mortality rate increases with Child’s class from about 20% for Child’s class A to over 60% for Child’s class C.
124
LaBRECQUE
Survival is improved with prompt resuscitation and appropriate therapy. Stabilization of the patient with actively bleeding varices is imperative and requires placement of two large bore intravenous lines and rapid replacement of intravascular volume with saline and colloid. The latter is best composed of packed red cells and, if there is severe coagulopathy, fresh-frozen plasma. Care must be taken not to over-expand intravascular volume. Older patients may have cardiac or pulmonary problems, which could rapidly result in complications from fluid overload. In addition, a too rapid expansion of plasma volume can lead to increased portal pressure and reinitiate the variceal bleed?, Excessive saline infusion is likely to produce, or worsen, ascites and edema whereas too much free water in the form of 5% dextrose in water often causes hyponatremia. For actively bleeding patients, antibiotics should also be provided. Up to 25% of patients with variceal bleeds will be bacteremic. However, aminoglycosides should be strictly avoided because of their high propensity for producing renal failure in patients with severe liver disease: This is a particular problem if they also have ascites as the likelihood of spontaneous bacterial peritonitis is greatly increased and these patients are the most sensitive to the renal toxic effects of aminoglyc~sides.~~ Several additional caveats should be kept in mind. Measurement of central venous pressure or even wedged pulmonary pressure may give a misleading indication of volume status due to the marked peripheral vasodilitation and splachnic pooling typical of cirrhotics. (See article by Gupta et al.) Conversely, a patient can lose up to 25% of his or her blood volume without a fall in blood pressure or rise in heart rate and a variceal bleed may present with simple hematochezia or melena. Orthostatic (upright) blood pressure and heart rate must always be taken in the suspected variceal bleeder and urine output strictly monitored. Failure to recognize the degree of blood loss and volume compromise can delay institution of necessary therapy and adversely affect the outcome. Adequacy of replacement is best judged by lack of hypotension and tachycardia, even on standing, and return of good urine output, rather than achievement of a preconceived level of hemoglobin. Similarly, the prothrombin time need not be completely corrected so long as the bleeding has been controlled. One should not "chase" the PT, trying to keep it in some arbitrary normal range. The latter is more likely to produce fluid overload and ultimately pulmonary edema with subsequent death of the patient rather than prevent rebleeding. Once the patient has been stabilized, usually in an intensive care unit, the patient should be evaluated for the cause of bleeding. If qualified personnel are not available, this may also be the window of opportunity to transfer the patient to a hospital with more sophisticated facilities. Even before the cause of bleeding has been identified, it may be appropriate to start pharmacological therapy empirically if a variceal bleed seems most likely. Octreotide (50 microgram bolus intravenously followed by a 50 microgram infusion per hour) is currently the most
A COMMONSENSE APPROACH TO VARICEAL BLEEDING
125
popular vasoactive regimen in the United States due to its apparent effectiveness in stopping bleeding with very few serious side effects. This is in contrast to the previously widespread use of vasopressin which requires concommitant administration of nitroglycerin to counteract the risks of significant ischemia to the heart and other organs. Therapy is usually continued for five days. (see article by Grace and Bhattacharya for a detailed discussion). Because these agents reduce portal pressure, they may be helpful whether the cause of the bleed is esophageal varices, gastric varices or portal hypertensive gastropathy. No technique replaces endoscopy in determining the cause of the bleed. It is critical to remember that 25% to 50% of patients with known varices who present with bleeding will actually be bleeding from sites other than their varices. Gastritis often from alcohol ingestion, use of nonsteroidal anti-inflammatory agents (NSAIDS), or a combination of the two, as well as Mallory-Weiss tears and ulcer disease are frequently the cause of the bleed and treatment must be changed accordingly. Placement of a nasogastric tube will obviate the need for lower GI evaluation if fresh blood, blood clots or coffee ground material is aspirated. Lack of a positive nasogastric aspirate does not rule out an upper GI source because varices may have stopped bleeding and duodenal ulcers sometimes fail to reflux blood into the stomach through a competent pyloric valve. Protection of the airway is essential during endoscopy to prevent aspiration pneumonia. Some advocate short term endotracheal intubation during the initial endoscopy. This is especially important in the patient who has ongoing hemetemesis, is encephalopathic or is unstable despite vigorous resuscitation. Skilled placement of the endotracheal tube is critical to avoid aspiration during intubation. It is always unfortunate if the acute bleed is effectively controlled only to have the patient die of aspiration pneumonia acquired during the procedure. Only endoscopy will accurately identify gastritis and portal hypertensive gastropathy. If the bleed does originate from a varix, treatment can be initiated and directed at the precise site of bleeding at the time of endoscopy. Sclerotherapy or band ligation is effective in stopping the bleed up to 90% of the time. As more physicians become skilled in its use, band ligation is likely to replace sclerotherapy in ail but the most actively bleeding cases due to its apparent equal efficacy with fewer side effects and the need for fewer sessions to completely obliterate the varices (see article by Slosberg and Keefe). While this flurry of diagnostic and therapeutic activity is taking place, the cause of the liver disease and its severity (Child’s class) must be determined. Other complications must be attended to, and plans made as to how future bleeds are to be handled. Such decisions should be made preemptively rather than in the throes of the next emergent bleed. Up to 10% of patients will not be controlled and will require further measures. The options are limited to TIPS, emergent shunt surgery or liver transplantation. Balloon tamponade is reserved as a temporizing measure in patients not controlled by vasoactive drugs and sclero-
126
LaBRECQUE
therapy/variceal ligation. Because of the high failure rate and many complications of balloon placement in unpracticed hands, its use is not recommended in the nonspecialized center. In the recalcitrant bleeder (defined as bleeding that is not controlled or that recurs despite two endoscopic therapeutic sessions and appropriate pharmacologic therapy), transjugular-intrahepatic porto-systemic shunt (TIPS) is the treatment of choice in an increasing number of centers. This is especially true if the patient is considered a candidate for later liver transplantation and the TIPS can be used to control the bleeding and serve as a bridge to stabilize the patient while awaiting availability of an organ. It may also serve as definitive therapy for the Child’s class C patient who is not a candidate for transplant but is at an unacceptably high level of risk for shunt surgery. Shunts are generally reserved for patients who have excellent liver function and whose only complication is uncontrolled or recalcitrant bleeding. Generally, these will be Child’s class A or “good” Child’s class B patients. Obviously, both of these options require the presence of individuals skilled in the performance of such procedures and emphasize the need for appropriate early referral if such options are not available at the center where the patient is initially treated (see articles by Ianitti and Henderson, Faust and Sorrell, and Sudan and Shaw). PREVENTING FUTURE BLEEDS
Once a patient has bled from varices, they are almost certain to bleed again if untreated. Roughly, two thirds of patients will rebleed within the next one to two years with a mortality of over 50% (see article by Boyer). Because of this high risk, preventive therapy is clearly indicated in all patients. Vasoactive drugs (propranolol, nadolol, long acting nitrates) are the first line of therapy and will reduce the risk of rebleeding while probably improving life expectency as In the U.S., most practitioners also continue sclerotherapy or banding every 13 weeks until the esophageal varices are completely obliterated. Band ligation is rapidly becoming the prefered method because it requires fewer sessions and produces fewer complications, especially strictures, and may reduce mortality compared to injection sclerotherapy. Once obliterated, surveillence endoscopy is carried out at progressively longer intervals in order to treat new varices while they are still small. With gastric varices and portal hypertensive gastropathy, only pharmacologic therapy is possible. In difficult cases, and those in which the portal pressure cannot be reduced sufficiently, some will combine the use of a beta blocker (e.g., nadolol 40 mg daily with isosorbide mononitrate 20 mg twice daily).I3 Reducing the portal pressure to less than 12 mmHg appears to produce almost complete protection from future bleeding.” All of these therapies merely treat a complication of the underlying disease process. If the disease itself cannot be arrested, liver failure will ultimately ensue. Patients with alcoholic cirrhosis can significantly
’
A COMMONSENSE APPROACH TO VARICEAL BLEEDING
127
increase their longevity by merely stopping drinking? which not only decreases future damage but can also reduce portal pressure if the portal inflammation and edema associated with alcoholic hepatitis is present. Similarly, reducing the inflammation and continued cell necrosis in chronic viral or autoimmune hepatitis may slow progression and help to prevent further complications. In the patient who continues to bleed, the options are the same as for the acute first time bleeder, TIPS, shunt surgery and transplantation (see articles by Slosberg and Keefe, Ianitti and Henderson, and Sudan and Shaw).
References 1. Albillos A, Paramo MP, Cacho G, et al: Accuracy of the noninvaslve measurements of portal (PBF) and forearm blood flow (FBF) in the assessment of the portal pressure response to propranolol. Hepatology 24:206A, 1996 la. Angelic0 M, Carli L, Piat C, et al: Isosorbide-5-mononitrateversus propranolol in the prevention of first bleeding in cirrhosis. Gastroenterology 104:1460-1465, 1993 2. Bernard B, Lebrec D, Mathurin P, et a1 Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in patients with cirrh&is: a meta-analysis. Hepa tology 25163-70, 1997 3. Boyer JL, Chatterjee C, Iber F et a1 Effects of plasma-volume expansion on portal hypertension. N Engl J Med 275:750, 1966 4. D’Amico G, Pagliaro L, and Bosch J: The treatment of portal hypertension: A metaanalytic review. Hepatology 22:332-354, 1995 5. Kravetz D, Bosch J, Anderiu M, et al: Hernodynamic effects of blood volume restriction following hemorrhage in rats with portal hypertension due to cirrhosis of the liver: Influence of the extent of portal systemic shunting. Hepatology 9:808, 1989 5a. Lietman P S Liver Disease, aminoglycoside antibiotics, and renal dysfunction. Hepatology 8:96&968,1988 6. Moore RD, Smith CR, and Lietman P S Increased risk of renal dysfunction due to interaction of liver disease and aminoglycosides. Am J Med 801093, 1986 7. Pagliaro L, D’Amico G, SorensenTIA, et al: Prevention of first bleeding in cirrhosis: A a meta-analysis of randomized trials of nonsurgical treatment. AM Intern Med 11759-70, 1992 8. Pinto HC, et al: Long term prognosis of patients with cirrhosis of the liver and upper gastrointestinal bleeding. Am J Gastroenterol84:1239, 1989 9. Powell WJ and Klatskin G: Duration of survival in patients with Laennec’s cirrhosis. Am J Med 44406,1968 10. Teran JC, Imperiale TF, Mullen KD, et a1 Primary prophylaxis of variceal bleeding in cirrhosis: A cost-effectiveness analysis. Gastroenterology 112473-482, 1997 11. Villanueva C, Balanzo J, Novella MT, et al: Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding. N Engl J Med 3341624-1629, 1996 12. Viudez P, Castafio G, Carlevaro 0, et al: Comparative study between duplex-Doppler U.S. and invasive hemodynamic measurements: response to I.V. propanolol in cirrhotic patients with hypertension. Hepatology 24205A, 1996
Address reprint requests to Douglas R. LaBrecque, MD Director, Liver Service Department of Internal Medicine University of Iowa Hospitals and Clinics 4553 JCP Iowa City, IA 52242-1081
1089-3261/97 $0.00
+ .20
A COMMONSENSE APPROACH TO VARICEAL BLEEDING Douglas R. LaBrecque, MD, FACP
INTRODUCTION Hematemesis due to acute variceal bleeding is the most dramatic and frightening consequence of portal hypertension, and with good reason. As noted in the preceeding articles, up to fifty percent of patients do not leave the hospital alive following their initial variceal bleed. As our understanding of the causes of acute variceal bleeding has increased, the esophageal varix has come to be viewed more and more as a dormant volcano, needing only an appropriate rise in pressure to breach its already stretched and progressively thinning endothelial covering. In the face of such potentially dire consequences, great efforts have been expended to prevent the first bleed, to treat the first bleed more successfully and to prevent future bleeds. Details of the various approaches currently available and those still under investigation, the rationale behind the different therapeutic choices, and extensive bibliographies supporting these choices are contained in the preceeding articles. From a careful reading of these articles one can develop a reasonable, rational, cost effective approach to variceal bleeding in the patient with cirrhosis and portal hypertension. However, the best approach varies depending on the technology and expertise available at a particular location. Ideally, the patient with an acute variceal bleed will be taken to a medical center with excellent emergency facilities and an intensive care unit experienced in the care of acute variceal bleeders where he or she From the Liver Service, University of Iowa Hospitals and Clinics; and the Veterans Administration Medical Center, Iowa City, Iowa
CLINICS IN LIVER DISEASE
-
-
VOLUME 1 NUMBER 1 MAY 1997
121
122
LaBRECQUE
can be rapidly evaluated and resuscitated by a team comprised of a hepatologist, endoscopist, therapeutic radiologist and hepatobiliary/ transplant surgeon. However, many are first taken to a smaller hospital which may lack one or all of the above. This article attempts to summarize a reasonable approach to the patient at the different points of presentation: (1)before the initial bleed; (2) at the time of an acute bleed; and (3) following an acute bleed. Detailed discussions of the procedures recommended and extensive literature supporting the recommendations can be found in the preceeding articles and are not repeated here. PREVENTING THE FIRST BLEED
Varices rarely bleed until the portal pressure equals or exceeds 12 mmHg (see articles by Gupta et a1 and Boyer). This level of portal pressure is not usually reached in the absence of cirrhosis, although there are important exceptions (see article by Lebrec et al). Prophylaxis to prevent variceal bleeding starts with the recognition that the patient has cirrhosis and documentation of the presence of portal hypertension. The importance of recognizing physical findings which suggest portal hypertension or advanced liver disease, historical indications of portal hypertension, and more subtle signs of variceal bleeding, cannot be overemphasized. Minor hematochezia or iron deficiency anemia rather than dramatic, life threatening hematemesis may be the only indication of variceal bleeding. One must first recognize the presence of portal hypertension before one can treat it prophylactically. The patient with chronic liver disease as evidenced by 6 months of elevated transaminases or physical evidence of chronicity (splenomegaly, prominent abdominal collaterals, ascites, hepatic encephalopathy) should have an abdominal ultrasound performed with doppler examination to rule out hepatic, portal or splenic vein obstruction, look for the presence of collaterals or a patent umbilical vein, and rule out hepatic or other intraabdominal masses. This can be complemented by CT examination, which will provide a clearer anatomic evaluation of the liver and is better able to visualize the pancreas and splenic vasculature which are often obscured by stomach gas. A liver biopsy should be performed to document the presence of cirrhosis and attempt to determine the etiology of the underlying liver disease. Appropriate serologic tests should also be performed to rule out viral, autoimmune, inherited, and metabolic causes. Pharmaciologic therapy is clearly beneficial in preventing the first esophageal variceal bleed in patients with Child’s Class A or B cirrhosis. Its value in patients who are Child’s class C is less clear (See article by Grace and Bhattacharya). A portal pressure above 12 mm Hg is probably the best indicator of potential for a variceal bleed but is not routinely available at most centers. Based on the expectation that approximately 50% of cirrhotics will have esophageal varices, the 1996 AASLD Conference on Portal Hypertension recommended routine endoscopy in cir-
A COMMONSENSE APPROACH TO VARlCEAL BLEEDING
123
rhotics to determine if varices were present. Several findings at endoscopy have been associated with a high risk of variceal hemorrage and are a reasonable substitute for measurement of the portal pressure. These include the presence of large varices, red wale markings and cherry red spots (see article by Boyer). In the presence of such findings in a patient with Child’s Class A or B cirrhosis, the patient should be started on a noncardiac selective beta blocker, typically 40 mg twice daily of propranolol or nadalol 40 mg per day. The dose is adjusted upwards to reduce the resting heart rate by 25 percent or to a rate of 55 to 60 beats per minute. Such a regimen can be expected to reduce the risk of bleeding and increase survival as well.7The cost effectiveness of prophylactic therapy in patients with small varices and none of the risk factors lised above is less clear, although many clinicians will choose to treat any patient with varices, regardless of size. A recent study has documented that propranolol is the only cost effective form of prophylactic therapy to prevent the initial variceal bleed in cirrhotics regardless of the risk of bleeding. Propranolol also increased the quality-adjusted life expectancy. Sclerotherapy was much less cost effective and did not increase life expectancy. And while shunt surgery was quite effective in decreasing the risk of bleeding, it also decreased overall life expectancy due to increased deaths from liver failure and hepatic encephalopathy, and was not cost effective.’O (A more detailed discussion of the overall cost-effectiveness of various strategies of treating the problem of variceal bleeding can be found in the article by Gralnek and Jensen.) When available, portal pressure should be measured prior to treatment and again 2 to 3 months later to document a drop to below 12 mmHg or at least 20% below the pretreatment value. In most centers, however, this will not be practical and the heart rate adjustment referred to above is an acceptable surrogate parameter with which to judge the effectiveness of therapy. Two recent abstracts1,l2 suggest that Doppler ultrasound assessment of portal venous blood flow may also serve as a reliable surrogate marker of a drop in portal pressure. Unfortunately, up to a quarter of patients may not tolerate longterm therapy with propranolol due to underlying cardiac or pulmonary disease, asthma, insulin dependent diabetes or other medical contraindications. For such patients, nadolol may be better tolerated. Another option is the use of long-acting nitrates. Although less well studied, isosorbide-5 mononitrate was found to be as effective as propranolol in one controlled trial.’
MANAGING THE FIRST VARICEAL BLEED
Historically, up to 50% of patients have died at the time of their first variceal bleed and variceal bleeding is the cause of death in about one third of all cirrhotics. Mortality rate increases with Child’s class from about 20% for Child’s class A to over 60% for Child’s class C.
124
LaBRECQUE
Survival is improved with prompt resuscitation and appropriate therapy. Stabilization of the patient with actively bleeding varices is imperative and requires placement of two large bore intravenous lines and rapid replacement of intravascular volume with saline and colloid. The latter is best composed of packed red cells and, if there is severe coagulopathy, fresh-frozen plasma. Care must be taken not to over-expand intravascular volume. Older patients may have cardiac or pulmonary problems, which could rapidly result in complications from fluid overload. In addition, a too rapid expansion of plasma volume can lead to increased portal pressure and reinitiate the variceal bleed?, Excessive saline infusion is likely to produce, or worsen, ascites and edema whereas too much free water in the form of 5% dextrose in water often causes hyponatremia. For actively bleeding patients, antibiotics should also be provided. Up to 25% of patients with variceal bleeds will be bacteremic. However, aminoglycosides should be strictly avoided because of their high propensity for producing renal failure in patients with severe liver disease: This is a particular problem if they also have ascites as the likelihood of spontaneous bacterial peritonitis is greatly increased and these patients are the most sensitive to the renal toxic effects of aminoglyc~sides.~~ Several additional caveats should be kept in mind. Measurement of central venous pressure or even wedged pulmonary pressure may give a misleading indication of volume status due to the marked peripheral vasodilitation and splachnic pooling typical of cirrhotics. (See article by Gupta et al.) Conversely, a patient can lose up to 25% of his or her blood volume without a fall in blood pressure or rise in heart rate and a variceal bleed may present with simple hematochezia or melena. Orthostatic (upright) blood pressure and heart rate must always be taken in the suspected variceal bleeder and urine output strictly monitored. Failure to recognize the degree of blood loss and volume compromise can delay institution of necessary therapy and adversely affect the outcome. Adequacy of replacement is best judged by lack of hypotension and tachycardia, even on standing, and return of good urine output, rather than achievement of a preconceived level of hemoglobin. Similarly, the prothrombin time need not be completely corrected so long as the bleeding has been controlled. One should not "chase" the PT, trying to keep it in some arbitrary normal range. The latter is more likely to produce fluid overload and ultimately pulmonary edema with subsequent death of the patient rather than prevent rebleeding. Once the patient has been stabilized, usually in an intensive care unit, the patient should be evaluated for the cause of bleeding. If qualified personnel are not available, this may also be the window of opportunity to transfer the patient to a hospital with more sophisticated facilities. Even before the cause of bleeding has been identified, it may be appropriate to start pharmacological therapy empirically if a variceal bleed seems most likely. Octreotide (50 microgram bolus intravenously followed by a 50 microgram infusion per hour) is currently the most
A COMMONSENSE APPROACH TO VARICEAL BLEEDING
125
popular vasoactive regimen in the United States due to its apparent effectiveness in stopping bleeding with very few serious side effects. This is in contrast to the previously widespread use of vasopressin which requires concommitant administration of nitroglycerin to counteract the risks of significant ischemia to the heart and other organs. Therapy is usually continued for five days. (see article by Grace and Bhattacharya for a detailed discussion). Because these agents reduce portal pressure, they may be helpful whether the cause of the bleed is esophageal varices, gastric varices or portal hypertensive gastropathy. No technique replaces endoscopy in determining the cause of the bleed. It is critical to remember that 25% to 50% of patients with known varices who present with bleeding will actually be bleeding from sites other than their varices. Gastritis often from alcohol ingestion, use of nonsteroidal anti-inflammatory agents (NSAIDS), or a combination of the two, as well as Mallory-Weiss tears and ulcer disease are frequently the cause of the bleed and treatment must be changed accordingly. Placement of a nasogastric tube will obviate the need for lower GI evaluation if fresh blood, blood clots or coffee ground material is aspirated. Lack of a positive nasogastric aspirate does not rule out an upper GI source because varices may have stopped bleeding and duodenal ulcers sometimes fail to reflux blood into the stomach through a competent pyloric valve. Protection of the airway is essential during endoscopy to prevent aspiration pneumonia. Some advocate short term endotracheal intubation during the initial endoscopy. This is especially important in the patient who has ongoing hemetemesis, is encephalopathic or is unstable despite vigorous resuscitation. Skilled placement of the endotracheal tube is critical to avoid aspiration during intubation. It is always unfortunate if the acute bleed is effectively controlled only to have the patient die of aspiration pneumonia acquired during the procedure. Only endoscopy will accurately identify gastritis and portal hypertensive gastropathy. If the bleed does originate from a varix, treatment can be initiated and directed at the precise site of bleeding at the time of endoscopy. Sclerotherapy or band ligation is effective in stopping the bleed up to 90% of the time. As more physicians become skilled in its use, band ligation is likely to replace sclerotherapy in ail but the most actively bleeding cases due to its apparent equal efficacy with fewer side effects and the need for fewer sessions to completely obliterate the varices (see article by Slosberg and Keefe). While this flurry of diagnostic and therapeutic activity is taking place, the cause of the liver disease and its severity (Child’s class) must be determined. Other complications must be attended to, and plans made as to how future bleeds are to be handled. Such decisions should be made preemptively rather than in the throes of the next emergent bleed. Up to 10% of patients will not be controlled and will require further measures. The options are limited to TIPS, emergent shunt surgery or liver transplantation. Balloon tamponade is reserved as a temporizing measure in patients not controlled by vasoactive drugs and sclero-
126
LaBRECQUE
therapy/variceal ligation. Because of the high failure rate and many complications of balloon placement in unpracticed hands, its use is not recommended in the nonspecialized center. In the recalcitrant bleeder (defined as bleeding that is not controlled or that recurs despite two endoscopic therapeutic sessions and appropriate pharmacologic therapy), transjugular-intrahepatic porto-systemic shunt (TIPS) is the treatment of choice in an increasing number of centers. This is especially true if the patient is considered a candidate for later liver transplantation and the TIPS can be used to control the bleeding and serve as a bridge to stabilize the patient while awaiting availability of an organ. It may also serve as definitive therapy for the Child’s class C patient who is not a candidate for transplant but is at an unacceptably high level of risk for shunt surgery. Shunts are generally reserved for patients who have excellent liver function and whose only complication is uncontrolled or recalcitrant bleeding. Generally, these will be Child’s class A or “good” Child’s class B patients. Obviously, both of these options require the presence of individuals skilled in the performance of such procedures and emphasize the need for appropriate early referral if such options are not available at the center where the patient is initially treated (see articles by Ianitti and Henderson, Faust and Sorrell, and Sudan and Shaw). PREVENTING FUTURE BLEEDS
Once a patient has bled from varices, they are almost certain to bleed again if untreated. Roughly, two thirds of patients will rebleed within the next one to two years with a mortality of over 50% (see article by Boyer). Because of this high risk, preventive therapy is clearly indicated in all patients. Vasoactive drugs (propranolol, nadolol, long acting nitrates) are the first line of therapy and will reduce the risk of rebleeding while probably improving life expectency as In the U.S., most practitioners also continue sclerotherapy or banding every 13 weeks until the esophageal varices are completely obliterated. Band ligation is rapidly becoming the prefered method because it requires fewer sessions and produces fewer complications, especially strictures, and may reduce mortality compared to injection sclerotherapy. Once obliterated, surveillence endoscopy is carried out at progressively longer intervals in order to treat new varices while they are still small. With gastric varices and portal hypertensive gastropathy, only pharmacologic therapy is possible. In difficult cases, and those in which the portal pressure cannot be reduced sufficiently, some will combine the use of a beta blocker (e.g., nadolol 40 mg daily with isosorbide mononitrate 20 mg twice daily).I3 Reducing the portal pressure to less than 12 mmHg appears to produce almost complete protection from future bleeding.” All of these therapies merely treat a complication of the underlying disease process. If the disease itself cannot be arrested, liver failure will ultimately ensue. Patients with alcoholic cirrhosis can significantly
’
A COMMONSENSE APPROACH TO VARICEAL BLEEDING
127
increase their longevity by merely stopping drinking? which not only decreases future damage but can also reduce portal pressure if the portal inflammation and edema associated with alcoholic hepatitis is present. Similarly, reducing the inflammation and continued cell necrosis in chronic viral or autoimmune hepatitis may slow progression and help to prevent further complications. In the patient who continues to bleed, the options are the same as for the acute first time bleeder, TIPS, shunt surgery and transplantation (see articles by Slosberg and Keefe, Ianitti and Henderson, and Sudan and Shaw).
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Address reprint requests to Douglas R. LaBrecque, MD Director, Liver Service Department of Internal Medicine University of Iowa Hospitals and Clinics 4553 JCP Iowa City, IA 52242-1081