Gastroesophageal variceal bleeding is an unpredictable complication of cirrhosis with an associated mortality of 15 to 30% with each bleeding episode, and about one-third of all deaths in patients with cirrhosis could be directly attributed to acute variceal bleeding. Prevention of first bleeding (primary prophylaxis) is therefore as important as treatment of acute bleeding and secondary prophylaxis. Patients with large varices or red signs, and those with an elevated hepatic venous wedge pressure gradient (> 12 mm Hg), should be treated with nonselective β-blockers to prevent the first bleed. Those who present with acute bleeding should be managed in an optimal fashion to reduce early mortality.
The past decade has seen tremendous progress in the management of acute variceal bleeding. A large number of randomized, controlled studies have been published on this topic comparing various treatment options, but these studies have uniformly lacked the sample size to show an improvement in survival. However, careful observations based on these studies, as well many meta-analyses performed on these studies, have made it possible for the clinicians to devise better strategies to manage these patients.
Resuscitative Measures
Management of acute variceal bleeding includes general resuscitative measures and specific treatment aimed at arresting the variceal bleeding. It is important to protect airways in an encephalopathic patient, particularly during endoscopic procedures and balloon tamponade, since aspiration pneumonia is a major cause of morbidity and mortality in these patients. Measurement of central venous pressure is a sensitive guide to the blood volume status but caution should be exercised in the presence of tense ascites because diaphragmatic compression of the right atrium by the ascites may lead to an overestimation of the readings.
Pulmonary capillary wedge pressure is the most accurate guide to control blood volume and may be invaluable in the presence of major ongoing bleeding. Blood volume restitution should be prompt and as accurate as possible to protect vital organs, particularly renal function. The ideal replacement fluid is blood and colloid is reserved for immediate infusion until blood becomes available. Isovolemic replacement should be the aim with care taken to avoid major overexpansion of the circulation that may precipitate further bleeding due to the associated increase in portal pressure. There is increasing evidence to support routine prophylactic antibiotics in those with ascites and in those with active bleeding. Control of bleeding is slower in patients with bacterial infection. It is therefore important to detect and treat complications, such as aspiration pneumonia and spontaneous bacterial peritonitis, at the earliest opportunity.
Because bleeding from a nonvariceal source is common in chronic liver disease, endoscopy should be performed when patient is stabilized. This may also be the ideal time to perform a therapeutic procedure to stop bleeding or prevent early rebleeding. If variceal bleeding is suspected, pharmacological treatment should be initiated while the patient is resuscitated before endoscopic confirmation of gastroesophageal variceal bleeding. Early pharmacologic treatment may improve the efficacy of endoscopic treatment as well as the survival.
Pharmacologic Treatment
Endoscopic Therapy
Endoscopic Sclerotherapy
Endoscopic sclerotherapy has an efficacy rate of 75 to 90%. Endoscopic band ligation is an alternative to sclerotherapy. Meta-analytical studies have shown that hemostasis rates with band ligation are comparable to sclerotherapy in patients with active variceal bleeding. However, no specific benefits have been shown for this technique over injection sclerotherapy during active bleeding. Band ligation has been found to be safe in children with acute variceal bleeding. Although endoscopic treatment may be marginally better than somatostatin/octreotide in some meta-analytical studies, many carefully performed studies and a recent meta-analysis have failed to show any significant advantage for either form of treatment when used alone. Moreover, sclerotherapy was associated with more adverse events than somatostatin/ octreotide.
Band Ligation, Tissue Adhesives
About 15 to 20% of patients treated with endoscopic sclerotherapy develop complications such as bleeding postsclerotherapy ulcers, esophageal stenosis, or perforation of esophagus. It is likely that the complication rates are lower with band ligation. Tissue adhesives such as n-butyl-2-cyaoacrylate have also been used by intravariceal injection to obliterate varices. Tissue adhesives are not approved for intravariceal injection in the United States, but studies from elsewhere have claimed control of bleeding in approximately 90% of cases.
The specific role for this treatment may be to obliterate fundal varices that respond unreliably to intravariceal injection of sclerosant or band ligation. Cerebral toxicity has been reported with the use of intravariceal injection of tissue adhesives. Currently there is no convincing evidence to recommend routine use of tissue adhesives for esophageal variceal obliteration.
Combination of Endoscopic and Pharmacologic Treatment
A combination of continuous infusion of octreotide for 5 days along With either sclerotherapy or band ligation has been shown to be superior to either sclerotherapy or band ligation alone in reducing early rebleeding and mortality. The combination treatment appears to particularly benefit those patients with shock and ongoing bleeding. In addition, continuous infusion of octreotide also has been shown to be very effective in reducing bleeding from postsclerotherapy esophageal ulceration.
Other combination treatments, such as addition of isosorbide mononi-trate to somatostatin, have not been shown to have any advantage over somatostatin alone. The current evidence favors the use of a combination of endoscopic treatment with either octreotide or somatostatin. These drugs should be started prior to endoscopy and continued for 5 to 7 days after the bleeding episode.
Until recently, it was generally accepted that immediate endoscopic treatment is the optimum treatment for active variceal bleeding, but is critically dependent upon available expertise to attain these high success rates and to minimize complications. The optimum timing of endoscopic treatment with respect to the bleeding episode remains unanswered. The options are immediate treatment with the associated technical difficulties, or delayed treatment after temporary hemostasis is achieved using vasocon-strictive drugs.
Because the efficacy of somatostatin, octreotide or terlipressin is comparable to endoscopic treatment, it is reasonable to postpone endoscopy for treatment, as well as to confirm the diagnosis, until the patient is stabilized with pharmcologic intervention. Immediate endoscopic treatment could be reserved for nonresponders to pharmacologic intervention. To reduce early rebleeding, it is advisable to continue vasoconstrictors, such as somatostatin or octreotide (or terlipressin), for the first 5 to 7 days after the bleeding episode.
Predictors of Failure to Control Acute Variceal Bleeding
Recommendations
Nonselective p-blockers should be used for primary prophylaxis in patients with advanced liver disease and large varices. Optimal resuscitation in a timely fashion is crucial for a better outcome in patients with acute variceal bleeding. Pharmacologic intervention while the patient is resuscitated is safe and beneficial, and pharmacologic treatment should be continued for 5 to 7 days to prevent early rebleeding. Endoscopic diagnosis and therapy should be performed when patient is adequately resuscitated and stabilized. transjugular intrahep-aticportosystemic shunting or shunt surgery should be reserved for nonresponders to a combination of pharmacologic and endoscopic therapy, and should not be delayed when endoscopic therapy has failed on two separate occasions.
Bleeding fundal varices are managed by either early surgery or transjugular intrahep-aticportosystemic shunting, and balloon tamponade should be used to control active bleeding. If tissue adhesives are available, endoscopic treatment with these agents may be an alternate option for bleeding gastric or ectopic varices before considering surgery or transjugular intrahep-aticportosystemic shunting. A combination of p-blockers (+ nitrates) and endoscopic treatment (preferably banding) maybe a logical approach for secondary prophylaxis. transjugular intrahep-aticportosystemic shunting or shunt surgery should be reserved for patients who rebleed despite a combination of endoscopic and pharmacologic therapy. Liver transplantation is the treatment of choice for patients with advanced liver disease and recurrent variceal bleeding.
Inderal
Sandostatin
Corgard
Vasostrict
Jennifer is a clinical pharmacologist. She helps doctors of all medical specialties choose medications. Jennifer consults about drug dosage, interactions, and side effects.