https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840220145

The treatment of portal hypertension: A meta-analytic review

These updated guidelines on the management of variceal haemorrhage have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines which this document supersedes were written in 2000 and have undergone extensive revision by 13 members of the Guidelines Development Group (GDG). The GDG comprises elected members of the BSG liver section, representation from British Association for the Study of the Liver (BASL) and Liver QuEST, a nursing representative and a patient representative. The quality of evidence and grading of recommendations was appraised using the AGREE II tool.The nature of variceal haemorrhage in cirrhotic patients with its complex range of complications makes rigid guidelines inappropriate. These guidelines deal specifically with the management of varices in patients with cirrhosis under the following subheadings: (1) primary prophylaxis; (2) acute variceal haemorrhage; (3) secondary prophylaxis of variceal haemorrhage; and (4) gastric varices. They are not designed to deal with (1) the management of the underlying liver disease; (2) the management of variceal haemorrhage in children; or (3) variceal haemorrhage from other aetiological conditions.

https://gut.bmj.com/content/gutjnl/64/11/1680.full.pdf

UK guidelines on the management of variceal haemorrhage in cirrhotic patients

https://www.liver.theclinics.com/article/S1089-3261(05)70186-0/pdf

Natural history of portal hypertension in patients with cirrhosis.

Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients

BACKGROUND: Terlipressin (triglycyl lysine vasopressin) is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile. However, its effectiveness remains uncertain. OBJECTIVES: To determine if treatment with terlipressin improves outcome in acute esophageal variceal hemorrhage and is safe. SEARCH STRATEGY: Randomized clinical trials were identified by searching the following databases (November 1999): The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library (Issue 3, 1999), MEDLINE, EMBASE, Biosis, and Current Contents. The bibliographies of identified publications were checked. Experts in the field and the manufacturers of terlipressin were contacted. For the update of this review, no new randomized clinical trials were identified on any of the databases (October 2002). SELECTION CRITERIA: All randomized clinical trials, which compared terlipressin with: (a) placebo or no treatment, (b) balloon tamponade, (c) endoscopic treatment, (d) octreotide, (e) somatostatin and (f) vasopressin, in the setting of acute variceal hemorrhage. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. The primary outcome measure was mortality. Secondary outcomes were failure of initial hemostasis, rebleeding, procedures required for uncontrolled bleeding or rebleeding, transfusion requirements and length of hospitalization. MAIN RESULTS: Twenty studies were identified for all the comparison groups, involving 1609 patients. There were seven studies (with 443 patients) comparing terlipressin to placebo, five of which were considered to be high quality studies based on the Jadad scale. The meta-analysis indicates that terlipressin was associated with a statistically significant reduction in all cause mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88). Three studies (with 302 patients) were identified comparing terlipressin to somatostatin, two of which were high quality studies; only one high quality study (219 patients) comparing terlipressin to endoscopic treatment was identified. Within the limited power provided by these small numbers of patients, no statistically significant difference was demonstrated between terlipressin and either somatostatin or endoscopic treatment in any of the outcomes. For the remaining comparison groups (terlipressin versus balloon tamponade, terlipressin versus octreotide, and terlipressin versus vasopressin) only small, low quality studies were identified and no difference was demonstrated in any of the major outcomes. There was no significant difference between the terlipressin group and any of the comparison groups in the number of adverse events that caused death or withdrawal of medication. REVIEWER'S CONCLUSIONS: On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.

Terlipressin for acute esophageal variceal hemorrhage

In a double-blind trial 60% of acute variceal bleeding episodes were controlled with terlipressin (glypressin) compared with 37% in patients given placebo (NS). Rebleeding was more common in the placebo group so that at 5 days bleeding remained under control in 54% of patients treated with terlipressin compared with only 19% after placebo therapy (p less than 0.025). Blood transfusion requirements were similar in the two groups. Terlipressin appeared to be the most effective in those patients with severe hepatic dysfunction.

Irving Cobden

Papers

Placebo-controlled trial of terlipressin (glypressin) in the management of acute variceal bleeding.