Sample CAT

							      Somatostatin or Octreotide Not Effective in Decreasing Mortality or
           Transfusion in Acute Esophageal Varices Hemorrhage

Question
14yo boy is admitted to the PICU with acute esophageal varices hemorrhage on an octreotide
drip. Does this therapy decrease mortality or reduce transfusion requirement?

Clinical Bottom Lines

1. Acute variceal hemorrhage in the pediatric population is rare.
2. Randomized, controlled data regarding the use of somatostatin or octreotide in the
   management of acute variceal hemorrhage are only available in the adult literature.
3. Somatostatin does not decrease mortality compared with placebo in the management of acute
   variceal hemorrhage in adults (1,2).
4. The study summarized suggested an increased transfusion requirement with somatostatin
   compared with placebo in the management of acute variceal hemorrhage in adults. There was
   significant heterogeneity between studies with respect to this finding. The value of
   somatostatin or octreotide in the management of patients with acute variceal hemorrhage is
   questionable (1,2).
Summary of Key Evidence

1. 86 patients with suspected bleeding esophageal varices and verified or suspected cirrhosis of
   the liver were randomized in a double-blinded, controlled trial to receive somatostatin or
   placebo. Placebo and control groups had similar characteristics at the onset. (1)
2. Outcome measures after six weeks were survival, blood transfusions, episodes of bleeding,
   days with bleeding, use of Sengstaken-Blakemore tube, and complications. Analysis was on
   an intention to treat basis. (1)
3. No significant differences were found between any outcome measures between the two
   groups. There were 16 deaths out of 42 patients in the somatostatin group compared with 16
   deaths out of 44 patients in the placebo group (p=1.00). There was an average of 8
   transfusions per patient given to patients in the somatostatin group compared with an average
   of 5 transfusions per patient in the placebo group (p=0.07). (1)
4. This study had insufficient power for a type II error of p=0.10. (1)

Additional Comments

   Somatostatin is a 14 amino acid hormone. Octreotide is an 8 amino acid derivative of
    somatostatin with a much longer half-life. Both have the same therapeutic properties.
   Somatostatin and octreotide reduce portal blood flow and hepatic venous pressure gradient
    but the effect on intra-esophageal pressure is more equivocal in experimental studies (2).
   Both drugs are well-tolerated. The major adverse effect is hyperglycemia with rare reports
    of insulin requirement for management (3).
   The Cochrane Database Review with a meta-analysis of 820 adult patients also found no
    difference in mortality with the use of somatostatin or octreotide vs. placebo (OR 1.04,
    95%CI 0.74-1.46). It reported a positive effect with drug for number of transfusions per
    patient, corresponding to 1.2U of blood product saved per patient (95%CI 0.8-1.6). This is
    likely not a clinically significant effect.(2)
   The use of somatostatin or octreotide in the management of acute non-variceal hemorrhage
    appears to significantly reduce the risk of continued bleeding but not alter the need for
    surgery nor decrease the transfusion requirement significantly. The effectiveness of the drug
    was limited to the subgroup with peptic ulcer bleeding. (3)

Citations

1. Gotzsche PC, Gjorup I, Bonnen H, Brahe NEB, Becker U, Burcharth F. Somatostatin v
   placebo in bleeding esophageal varices: randomised trial and meta-Analysis. BMJ 1995; 310:
   1495-8.
2. Gotzsch PC. Cochrane Database of Systematic Reviews: Somatostatin or octreotide for acute
   bleeding esophageal varices. The Cochrane Library 1999; Vol 2.
3. Siafakas C, Fox VL, Nurko S. Short communication: Use of octreotide for the treatment of
   severe gastrointestinal bleeding in children. J Pediatr Gastroenterol Nutr. 1998;26: 356-9.
4. Imperiale TF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and
   placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a
   meta-analysis. Ann Intern Med. 1997; 127: 1062-1071.



                                CAT Author: Angela Punnett, MD

                                CAT Appraisers: <Reviewers>, MD

                                     Date appraised: 7/26/99