Efficacy Endpoints: Mortality, Need for blood transfusions
Harm Endpoints: Cost, Delay in more effective therapy, adverse drug reactions
Narrative: Somatostatin analogues are used for emergent treatment of bleeding esophageal varices. This is a relatively rare medical emergency that is often fatal. This systematic review included 21 randomized trials (2588 patients) comparing somatostatin analogues to placebo or no treatment. The dose and length of treatment varied. The drugs did not reduce mortality. There was a reduction in the amount of blood transfused, with a treatment effect of 0.7 units of blood when only trials with a low risk of bias were included.
The addition of somatostatin analogues to usual resuscitation did not identifiably reduce the rate of death in patients with hemorrhage from esophageal varices in the studies reviewed. These drugs appear to reduce a surrogate marker, the amount of blood transfused. However reducing the amount of blood transfused seems important only as a stepping stone to reductions in mortality, which were not present. The reduction in this surrogate marker may, however, indicate a small, as yet undetected, reduction in mortality that would be identifiable only in a very large randomized trial. In addition, the reductions found in the review (0.7 units of blood) are of questionable clinical relevance as hospitals do not partition blood in less than 1 unit aliquots. Moreover, justification is often given to the use of these drugs because of reported benefits for initial hemostasis. As the review notes, this is often subjective and variably defined. If there is initial hemostasis but re-bleeding occurs in one to two days is this a treatment failure? Such variable definitions cannot be practicably utilized as trial or review endpoints and therefore should not be used as a primary justification for the use of these drugs.
Caveats: Heterogeneity is expected when studying esophageal varices as the threshold for giving blood, the decision to use balloon tamponade, and the access to emergency endoscopy will likely vary. Definitions of successful hemostasis and rebleeding are likely to vary as well. Additionally, it is a relatively rare emergency medical condition, and thus, it is difficult to get a consecutive patient sample group of patients (i.e. it is difficult to enroll all patients with a given condition consecutively, which would be the most valid method for enrollment, when the condition is relatively uncommon).
In addition, it has been suggested that when somatostatin analogues are combined with invasive measures such as sclerotherapy benefits may be more robust or statistically identifiable. This may represent a commonly used, multipronged approach to variceal bleeding in which somatostatin analogues play one role. Placebo controlled, randomized trials examining this question would help to determine if indeed somatostatin analogues may demonstrate benefits as a component of such an approach.
Author: Lucy Willis, MD
Published/Updated: October 6, 2010
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