Endoscopic Sclerotherapy Should Be
Second-Line Treatment for Variceal Bleeding
News Author: Laurie Barclay, MD
CME Author: Bernard M. Sklar, MD, MS
To earn CME credit, read the news brief,
the paragraphs that follow, and answer the questions below.
Release Date: May 29, 2003;
May 29, 2003 — A Cochrane meta-analysis reported in the
May issue of Gastroenterology suggests that endoscopic
sclerotherapy should be used to control variceal bleeding only
when pharmacologic therapy fails.
"Available evidence does not support emergency
sclerotherapy as the first-line treatment of variceal bleeding
in cirrhosis when compared with vasoactive drugs, which
control bleeding in 83% of patients," write Gennaro
D'Amico, MD, from Ospedale V Cervello in Palermo, Italy, and
colleagues. "Therefore, endoscopic therapy might be added
only in pharmacologic treatment failures."
Using MEDLINE (1968-2002), EMBASE (1986-2002), and the
Cochrane Library (2002), the investigators identified 15
randomized controlled trials comparing sclerotherapy with
vasopressin (with or without nitroglycerin), terlipressin,
somatostatin, or octreotide for variceal bleeding in
Although sclerotherapy was superior to vasopressin for the
control of bleeding in a single trial, this trial was flawed
by a potential detection bias. Otherwise, sclerotherapy was
not superior to vasopressin for rebleeding, blood
transfusions, death, or adverse events, and it was not
superior to terlipressin, somatostatin, or octreotide for any
Adverse events were significantly more common with
sclerotherapy than with somatostatin. Using a predefined
sensitivity analysis that combined all of the trials
regardless of the control treatment, the risk differences
between sclerotherapy and control were -0.03 (95% confidence
interval [CI], -0.06 to 0.01) for failure to control bleeding,
-0.035 (95% CI, -0.07 to 0.008) for mortality, and 0.08 (95%
CI, 0.02 to 0.14) for adverse events.
The difference in mortality risk was -0.01 (95% CI, -0.07
to 0.04) in good-quality trials and -0.08 (95% CI, -0.14 to
-0.02) in poor-quality trials. Six deaths were attributed to
sclerotherapy, compared with none in the vasoactive groups.
Although there were methodological problems in most of the
trials, the authors suggested that these problems tended to
exaggerate the beneficial effects of sclerotherapy,
particularly on survival, and to minimize adverse events.
"Adding endoscopic therapy only in failures of medical
treatment could save a large proportion of emergency
endoscopic treatments and related complications," the
authors write, noting that this approach could also reduce
healthcare costs. "It remains to be assessed whether the
immediate combination therapy is superior to endoscopic
therapy added to vasoactive drugs only when the pharmacologic
intervention fails. If the delayed combination is as equally
effective as the immediate combination, then a considerable
reduction of adverse events associated with emergency
endoscopic therapy might be expected. We suggest testing this
hypothesis in [a randomized clinical trial]."
Upon completion of this activity,
participants will be able to:
- Discuss the etiology,
prevalence, and treatment of bleeding esophageal varices.
- Describe the results of a
Cochrane meta-analysis comparing emergency sclerotherapy
with pharmacologic treatment for bleeding esophageal
Bleeding from esophageal varices is one of the most common
and severe complications of hepatic cirrhosis. According to
the textbook Schwartz Principles of Surgery, bleeding
esophageal varices or gastric varices in the presence of liver
disease account for about 10% of all upper gastrointestinal
bleeding and are a life-threatening situation with a high
Alcoholism is the most common cause of portal hypertension,
but hepatitis B and hepatitis C are increasingly seen as
causes of posthepatic cirrhosis. Hepatocellular carcinoma may
complicate hepatitis B and result in sudden onset of portal
hypertension with portal vein thrombosis and bleeding. In
patients with cirrhosis and portal hypertension, variceal
hemorrhage accounts for 50% to 75% of all episodes of upper
Variceal hemorrhage usually is precipitated by ulceration
of the varix secondary to reflux esophagitis or increased
pressure within the varix. Recurrent bleeding and mortality
follow the inability of the failing liver to synthesize
reparative proteins and proteins necessary for coagulation.
According to the authors of the Gastroenterology
study, sclerotherapy of esophageal varices is widely used and
has often been recommended as the first-choice treatment of
variceal bleeding in cirrhosis. This recommendation has
persisted in spite of studies showing that vasoactive drugs
may stop bleeding in most patients and the presence of several
randomized controlled trials comparing emergency sclerotherapy
with vasoactive drugs yielding inconsistent results. Bañares
and colleagues, in the March 2002 issue of Hepatology,
reported a meta-analysis showing that the efficacy of
emergency endoscopic sclerotherapy or banding ligation of
varices is significantly improved when combined with
somatostatin or its derivatives, although the combination did
not improve survival.
Emergency endoscopic therapy requires a skilled endoscopist,
and sclerotherapy is associated with adverse events in 10% to
20% of patients and with serious adverse events in 7%. The
efficacy of emergency banding ligation and its complications
are poorly defined because that procedure was assessed only in
a few randomized clinical trials for the long-term prevention
of variceal rebleeding.
Because either endoscopic or pharmacologic therapy have
been reported to control bleeding in 75% to 90% of patients,
initial treatment with the more effective therapy and their
combination only in failures of initial treatment might be a
more logical approach than their immediate combination.
For these reasons, the authors performed a systematic
review to assess the efficacy and adverse events of emergency
sclerotherapy compared with vasoactive drugs for acute
variceal bleeding in cirrhotic patients.
The study in Gastroenterology updates the November
2002 Cochrane Review, "Emergency sclerotherapy or band
ligation combined with vasoactive drugs for bleeding
esophageal varices in cirrhosis," by adding three
additional randomized clinical trials.
This is a meta-analysis comparing emergency sclerotherapy
with pharmacologic treatment. The authors searched MEDLINE
(1968-2002), EMBASE (1986-2002),and the Cochrane Library
(2002) to retrieve randomized controlled trials comparing
sclerotherapy with vasopressin (with or without
nitroglycerin), terlipressin, somatostatin, or octreotide for
variceal bleeding in cirrhosis.
Outcome measures were failure to control bleeding,
rebleeding, blood transfusions, adverse events, and mortality.
Fifteen trials were identified.
The study showed that sclerotherapy was not superior to
terlipressin, somatostatin, or octreotide for any outcome nor
to vasopressin for rebleeding, blood transfusions, death, or
adverse events; it was superior to vasopressin for the control
of bleeding in a single trial "flawed by a potential
detection bias." Sclerotherapy was associated with
significantly more adverse events than somatostatin.
The authors conclude that "available evidence does not
support emergency sclerotherapy as the first-line treatment of
variceal bleeding in cirrhosis when compared with vasoactive
drugs, which control bleeding in 83% of patients." They
suggest that "endoscopic therapy might be added only in
pharmacologic treatment failures."
Pearls for Practice
- Emergency sclerotherapy should
not be the first-line treatment of variceal bleeding in
- In the treatment of variceal
bleeding, endoscopic therapy should be added only when
vasoactive treatment fails.