A series about the cold, hard numbers behind some of our most common ED practices
edited by David H. Newman, MD
Q: Does it help to use prophylactic antibiotics during management of gastrointestinal bleeding in cirrhotic patients?
by Daniel P. Runde, MD
For every 4 pts treated with antibiotics, 1 infection is prevented; for every 22 pts treated, 1 death is prevented
Side effects were not well tracked in these studies, but were probably less common than benefits
Green: More benefit than harm
Take Home Message: Antibiotics for cirrhotics with upper GI bleeding appear to save lives by reducing infections.
Details: Cirrhotic patients often develop bleeding from gastric or esophageal varices that occur secondary to portal hypertension. Gastrointestinal (GI) bleeding is fatal in approximately 20% of these episodes and bacterial infections are an important contributor to this mortality. Patients with cirrhosis are also known to have impaired immune function and increased translocation of bacteria from the gut into the bloodstream, thus the administration of prophylactic antibiotics during the bleeding event has been proposed as a treatment to help prevent such infections.
This Cochrane Review includes 12 trials (n = 1241) of cirrhotic patients with upper GI bleeding. Only 1 was placebo controlled, the other 11 examined antibiotics vs. no intervention. These trials demonstrated a clear decrease in overall rate of bacterial infections, with marked reductions in bacteremia, pneumonia, spontaneous bacterial peritonitis and urinary tract infections. The trials also noted a decrease in mortality. The choice of antibiotic regimen appeared to have no effect, although all were chosen because of their activity against gram negative organisms, the most common infecting agents for the targeted infection types.
Caveats: These trials are of marginal quality, and only one was placebo-controlled. A large, high quality randomized trial on this question still needs to be done, however at the moment the best guess seems to be that antibiotics reduce both morbidity and mortality for these patients.
Data source: Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila FI, Soares-Weiser K, Uribe M. Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD002907. Review. PubMed PMID: 20824832.
Q: Do somatostatin analogues drugs improve survival or reduce morbidity during acute variceal bleeding?
by Lucy Willis, MD
No serious medical harms were identified
Red: Intervention proven to be of no benefit
Take Home Message: Somatostatin analogues like octreotide did not reduce morbidity or mortality in randomized trials of patients with variceal bleeding
Details: Somatostatin analogues, which decrease portal blood pressure (and theoretically, at least, may decrease GI bleeding in patients with cirrhosis and variceal bleeding) are often used for emergent treatment of bleeding esophageal varices, which 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 somatostatin analogues drugs may slightly reduce the amount of blood transfused, a physician discretionary measure that seems important only as a stepping stone to reductions in mortality, which was not affected. If this effect on transfusions represents an impact on mortality that is too small to be detected in the included trials, then only a very large randomized trial could answer this question. Importantly, justification is often given to the use of these drugs based on reported measures of 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 in trials and designs and outcomes is expected when studying variceal bleeding as the threshold for giving blood, the decision to use balloon tamponade, and the access to emergency endoscopy will vary. Definitions of successful hemostasis and rebleeding also vary. In addition, it has been suggested that when somatostatin analogues are combined with invasive measures such as sclerotherapy benefits may be more robust, and this may be 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. For the time being their lack of effect on mortality, and their negligible impact on even a surrogate marker (transfused blood) among over 2500 subjects with variceal bleeding suggests that the drugs are not beneficial and that resources would be better utilized on other interventions in these complex and resource-intensive patients.
Data source: Somatostatin analogues for acute bleeding oesophageal varices. Gøtzsche PC, Hróbjartsson A. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD000193. Review. PMID: 18677774
The NNT // Explained
The NNT offers a measurement of the impact of a medicine or therapy by estimating the number of patients that need to be treated in order to have an impact on one patient. The concept is statistical, but intuitive. After all, we know that not everyone is helped by a medicine or intervention—some benefit, some are harmed, and some are unaffected. The NNT and the NNH (number-needed-to-harm) tell us how many.
TheNNT.com is a project designed to make these estimates available for decisions at the bedside, and in conversations with patients. There’s a lot of data out there, TheNNT.com is just a place where it’s easy to find, and easy to use.
-David Newman, MD