Dig Dis 1992; 10(suppl l):30-37

University Department of Medicine, Hcpato-Biliary and Liver Transplantation Unit, Royal Free Hospital and School of Medicine, London, UK

Keyw ords Nitroglycerin Esophageal varices Drug therapy

Medical Management of Bleeding Esophageal Varices


Vasoactive drug therapy is the only therapy that can be admin­ istered immediately to patients with suspected variceal bleed­ ing. The optimal agent is not yet available, but somatostatin or octreotide, glypressin and vasopressin and nitroglycerin are the best candidates. Somatostatin and octreotide have the best therapeutic index as they have very few side effects. They compare well to the other agents in comparative randomized trials. In addition to being used prior to sclerotherapy, vasoac­ tive agents may show benefit when used in combination with endoscopic methods and in the immediate interval thereafter in order to prevent early re-bleeding. This remains to be tested in clinical trials.


Variceal bleeding is the most serious com­ plication of portal hypertension. Variceal veins in the esophageal and gastric submucosa are part of the portosystemic channels which develop when pressure increases in the portal venous bed. In these sites varices may rupture and bleed, irrespective of the cause of portal hypertension. Variceal bleeding may compli­ cate previously diagnosed cirrhosis or may be the first manifestation of chronic liver dis­ ease. Variceal bleeding should be treated in the context of a gastro-intestinal bleeding team, with intensive nursing care. Ideally, when lo­

cal expertise is not available, liaison with a tertiary centre should be established as soon as possible and transfer arranged if necessary. The goals of therapy are to arrest the haem­ orrhage using specific measures, but also to prevent deterioration of liver function and complications related to bleeding. In addi­ tion, because variceal bleeding is accompa­ nied by early re-bleeding within a few days of admission in at least 50% of patients [1-3] measures used to stop bleeding should also prevent this early re-bleeding. These thera­ peutic strategies should lead to an improved survival. The risk of continued variceal bleeding or early bleeding is related to the severity of liver

Dr. A.K. Burroughs University Department of Medicine Hepato-Biliary and Liver Transplantalion Unit Royal Free Hospital and School of Medicine Pondstrect. Hampstead. London NWj 2QG (UK)

© 1992 S. Karger AG, Basel 0257-2753/92/ 0107-0030$2.75/0

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Andrew K. Burroughs

Management of Acute Bleeding Diagnosis

Endoscopy is mandatory. Endoscopic diagnosis of a bleeding lesion in patients with liver disease allows appropriate management, as not all sources of bleeding are variceal. Endoscopy is performed without sedation once initial resuscitation is satisfactory. Nasal oxygen and pulse oximetry should be used. In difficult patients, or when moderate to severe encephalopathy is present, or indeed coma, endotracheal intubation and light anaesthesia are needed. This may be necessary during alcohol withdrawal in which case rapid deep sedation must be induced before endotracheal intubation. At endoscopy, the diagnosis of bleeding varices is made if there is: (a) a venous (non-pulsatile) spurt or venous ooze (b) platelet aggregate or fibrin clot (white nip­ ple) (c) rarely an adherent clot. When these signs are absent, a presump­ tive diagnosis is made providing no other lesions arc seen [9], Studies have shown that this presumptive diagnosis in this context is diagnostic of bleeding varices. If more than one non-bleeding lesion is seen, immediate re­ endoscopy is mandatory'. If re-bleeding oc­ curs. endoscopic studies have shown that it is due to bleeding varices in 75% of cases [ 10], Even when endoscopy is performed within 6 h of admission to hospital active variceal bleeding is seen in less than 30% of patients. Some centres do not perform emergency en­ doscopy unless the patient has clinical evi­ dence of continued bleeding and routinely perform endoscopy the morning after. In these cases emergency sclerotherapy is de­ layed. and other measures such as pharmaco­ logical control should be used in the interval to endoscopy.


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disease [ 1]. At the Royal Free Hospital, failure of transfusion of blood products and vasoac­ tive drugs within 5 days of admission oc­ curred in 21% of cirrhotics classified as Pugh's grade A. 40% of grade B and 63% of grade C. evaluated in a prospective study [ 1]. There is also some evidence that a higher hepatic venous pressure gradient (HPVG) which reflects portal pressure is associated with continued bleeding or early re-bleeding when measured on dav 1 or 2 after admission [4, 5]. Survival is also related to the severity of liver disease, but there are no measures that can improve liver cell function in the short term. In addition, renal dysfunction has been shown to be independently predictive of sur­ vival [6. 7] and a higher portal pressure mea­ sured within 2 weeks of bleeding [8]. Thus, there will always be a small group of patients who. despite rapid arrest of bleeding, will develop an irreversible worsening of liver function, or be unable to recover from com­ plications of bleeding, such as aspiration pneumonia, or renal failure which may have occurred before medical care could be insti­ tuted. However, this group of patients can never be identified a priori. Thus, unless a previous decision has been made not to treat future episodes of bleeding, a specific proto­ col of management should be used whenever variceal bleeding is suspected. At present it is not possible to select pa­ tients who may or may not respond to certain types of treatment. However, those with more decompensated cirrhosis respond less well, whatever the treatment used, so that the car­ dinal rule is not to delay using alternative modes of therapy, if the first one used fails. Moreover, in some patients it may not be pos­ sible to use a particular type of therapy, be­ cause of the presence of specific contraindica­ tions. or lack of expertise, so that alternative treatment protocols must be available.



U/min produces a similar reduction in wedged hepatic venous pressure as 0.4 U/min. which is the currently recommended infusion rate. Use of 0.2 U/min may reduce the incidence of side-effects. Moreover, there was no tachyphylaxis and no rebound portal pressure increase, and there was no difference in the HVPG between those who remained stable, continued to bleed, or re-bleed during vasopressin. Tsai et al. [12] have shown that vasopressin results in a smaller reduction in portal pressure in those cirrhotics with active bleeding from varices compared to those without, and a smaller reduction still, in those in shock compared to those without shock. These data may explain why the therapeutic efficacy of vasopressin has not been proven in randomized clinical trials, this especially con­ sidering the different doses and length of infu­ sion times and assessments for efficacy which have been used (table 1). The trial which shows vasopressin to be most effective only assessed the efficacy at one hour, and endoscopy did not exist to con­ firm the source of bleeding [ 13], The best con­ ducted trial, which was against placebo [16], showed no benefit of vasopressin (table I). There is little evidence that vasopressin has a useful therapeutic index [ 17], Many European centres, including the Royal Free Hospital, have not used vasopressin for many years, but it remains the principal drug in the USA, nowadays combined with nitroglycerin. Vasopressin and Nitroglycerin. The addi­ tion of nitro vasodilators significantly reduces the systemic side-effects of vasopressin whilst maintaining the hypotensive effect in the por­ tal venous bed [ 18]. Three studies (table 2) have shown that side-effects are significantly reduced using nitroglycerin, either sublin­ gually [19], or intravenously [20] or transdermally [21], Thus vasopressin, if used, should be combined with nitroglycerin. These au­ thors also claim that the combined therapy is

Medical Managemenl of Bleeding Esophageal Varices

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Pharmacological Control Drug therapy is the optimal first treatment for variceal bleeding because it is the only one that can be administered immediately. This is not the case for endoscopic measures or sur­ gery. Moreover, drug therapy does not require sophisticated equipment or specialized train­ ing. The optimal drug should be safe, effec­ tive. easy to administer, and any side effects should not require stopping the drug. It should not interfere with the other modalities of treatment. Currently available drugs do not fulfil all of these requirements, but their limi­ tations must be considered in the context in which they are used. Drug therapy is aimed at stopping bleeding by reducing blood How and pressure in the esophageal varices, thus allow­ ing haemostasis at the bleeding site. Vasopressin. Vasopressin has been in use for 40 years. Its significant drawback is vaso­ constriction of systemic regional circuits, par­ ticularly cardiac and skin arterioles. There may be also excessive constriction of splanch­ nic arterioles - this is its mode of action, thereby reducing portal inflow. Skin gan­ grene, myocardial infarction, and bowel gan­ grene have all been reported. Vasopressin is thus contraindicated in patients with known or suspected ischaemic heart disease. More­ over. 20-30% of patients need to suspend treatment because of cardiac side-effects heart failure, angina and arrhythmias. Recently, some haemodynamic studies have shown that cirrhotics have abnormal systemic pressor responses to prolonged ad­ ministration of vasopressin. Although peak increases in arterial pressure and reduction in heart rate and cardiac output with 0.4 U/min were similar to normal controls, cirrhotics maintained a higher blood pressure, systemic vascular resistance and elevated systemic oxy­ gen consumption in the long term without a return to near baseline levels as in the controls [11]. Ready et al. [4] have shown that 0.2

Table 1. Randomised trials of vasopressin versus placebo or no treatment


Mcrigan et al. [ 113] Conn et al. [14] Mallory et al. [ 15] Fogel et al. [ 16]


1962 1975 1980 1982

Patient Dose admissions units/min

Length infusion

53 33 12 33

20 min 7-74 h 1-196h 24 h


Medical management of bleeding esophageal varices.

Vasoactive drug therapy is the only therapy that can be administered immediately to patients with suspected variceal bleeding. The optimal agent is no...
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