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Three Part Question

In [adults with known varices] is [terlipressin or somatostatin] more effective at [reducing acute bleeding]?

Clinical Scenario

A 55 year old male presents with massive haematemesis. He has known oesophageal varices. He is tachycardic, peripherally shut down and continues to actively vomit fresh blood. You wonder if pharmacological treatment with terlipressin or somatostatin will be effective in reducing the bleeding.

Search Strategy

Medline OVID 1966-2005 February Week 1
Embase OVID 1980-2004 Week 7
[(exp Gastrointestinal Hemorrhage/ OR exp "Esophageal and Gastric Varices"/ or oesophageal varices.mp.)] AND [(exp SOMATOSTATIN/ AND terlipressin.mp. OR glypressin.mp. OR terlypressin.mp.)] LIMIT to humans and Eng Lang.

Search Outcome

170 papers were identified of which 4 were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Walker S et al 1992 Germany	50 episodes of endoscopically proven bleeding oesophageal varices in 33 patients	Double blinded randomised controlled trial	Cessation of active bleeding for 24 hours within 24 hours of randomisation	22/25 (80%) patients with terlipressin ceased bleeding whilst 19/25 (76%) of the somatostatin group ceased bleeding	Numbers too small to firmly exclude type 2 error No power study
Pedretti G et al 1994 Italy	60 patients, previously diagnosed with hepatic cirrhosis, with current endoscopically proven variceal bleeds	Unblinded randomised controlled trial	Cessation of acute bleed and occurrence of rebleeding inside 24 hours	No statistical difference in cessation of bleeding; Octreotide 76.6% (23/30) vs Terlipressin 53% (16/30)	Not blinded
Walker S et al 1996 Germany	106 patient episodes of bleeding from endoscopically proven bleeding varices episodes in 72 patients	Double-blinded placebo controlled clinical trial	Cessation of bleeding for a 24 hour period within 24 hours of trial recruitment	91% (48/53) of terlipressin treated episodes ceased bleeding with 81% (43/53) of the somatostatin treated episodes ceasing. Statistical significance not reached	The inclusion of patients with multiple episodes who had variable numbers of sclerotherapy sessions may have introduced some bias
Feu F et al 1996 Spain	161 patients with endoscopically proven acute oesophageal variceal bleeding	Double blind randomised controlled trial	Cessation of bleeding for a 24 hour period inside 36 hours of randomisation	Cessation of bleeding in 64/80 (80%) of patients treated with terlipressin and 68/81 (84%) of patients treated with somatostatin. Statistical significance not reached

Comment(s)

4 randomised controlled studies exist in this area. No significant difference in rates of cessation of bleeding was found between patients treated with either terlipressin or somatostatin.

Clinical Bottom Line

There appears to be no significant difference between terlipressin and somatostatin in their ability to control bleeding. The logistical advantage of 4 hourly bolus administration for terlipressin over the need for continuous infusions of somatostatin and the lower cost of terlipressin will be relevant when choosing between them.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. Walker S, Kreichgauer HP, Bode JC. Terlipressin vs. somatostatin in bleeding esophageal varices: a controlled, double-blind study. Hepatology 1992;15:1023-30.
2. Pedretti G, Elia G, Calzetti C, et al. Octreotide versus terlypressin in acute variceal hemorrhage in liver cirrhosis. Emergency control and prevention of early rebleeding. Clinical Investigator 1994;72(9):653-9.
3. Walker S, Kreichgauer HP, Bode JC. Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices--final report of a placebo-controlled, double-blind study. Zeitschrift fur Gastroenterologie 1996;34:692-8.
4. Feu F, Ruiz del Arbol L, Banares R, et al. Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Gastroenterology 1996;111:1291-9.