Somatostatin Treatment and Risk Stratification by Continuous Portal
Pressure Monitoring During Acute Variceal Bleeding
Gastroenterology 2001; 121:110-117
CR 黃樹人/VS 孫灼基
 Changes of portal pressure during follow-up, determined by the
hepatic venous pressure gradient (HVPG), provide better information
on the risk of variceal bleeding than a single measurement.
 Patients with a higher HVPG have a greater risk of further bleeding
and death; 20 mmHg is the best cutoff value for predicting evolution.
 Factors such as overtransfusion or the presence of blood in the gut
may increase portal pressure during acute bleeding.
 Somatostatin decreases splanchnic blood flow and portal pressure
without adverse effects on systemic circulation; however, its effects
on HVPG in cirrhotic patients are controversial.
 This study was performed to assess the effects of somatostatin by
continuously monitoring portal pressure and systemic hemodynamics
during esophageal variceal hemorrhage, and to investigate whether
changes of HVPG affect the course of the acute bleeding episode.
Patients and Methods
 Cirrhotic patients with acute esophageal variceal bleeding that was
initially controlled with emergency sclerotherapy (5% ethanolamine)
and in whom a hemodynamic evaluation could be performed within
the first 24 hours of admission.
 Exclusion criteria: treatment with beta blockers or other vasoactive
drugs within the previous 5 days, a Child-Pugh score > 12 points,
HCC, PV thrombosis, extrahepatic malignancies, or other severe
associated conditions.
 Hourly lavage via NG tube to assess the activity of hemorrhage
 Daily hemoglobin measurement (or earlier if indicated); transfusion
of PRBC to maintain Hb at approximately 9 g/dL.
Catheterization
 Within the first 24 hours of admission and at least 6 hours after
sclerotherapy.
 Swan-Ganz catheter to measure CO and cardiopulmonary pressures.
 7F balloon-tipped catheter placed in the main right hepatic vein and
kept for a 24-hour period for serial measurements of wedged
(occluded) and free hepatic venous pressures (WHVP and FHVP).
 Portal pressure was estimated from the HVPG, the difference
between WHVP and FHVP.
Study Protocol
 Patients were randomly assigned to receive a bolus injection of 250
ug of somatostatin followed by a 250 ug/h continuous intravenous
infusion, or an injection of placebo (saline) followed by a placebo
infusion.
 Infusions maintained during the first 5 days of admission, and
additional boluses of were administered every 12 hours throughout
this period.
 Serial measurements of HVPG, arterial blood pressure, and heart rate
were obtained at baseline and at 4 pm (10 to 20 minutes after
beginning drug infusion), 9 pm, 12 am, 8 am, 12 pm, and again at 4
pm, or until the catheter was dislodged.
 Additional measurements were obtained after blood transfusions, and
20 to 30 minutes after a standard liquid meal that was administered at
1 pm to patients with controlled bleeding.
 Further bleeding: failure to control acute bleeding or early
rebleeding.
 Failure:
hematemesis or bloody aspirates, associated with
hemodynamic instability (SBP < 100, HR > 100), or a fall in
hemoglobin level of 2 g/dL or more in less than 6 hours.
 Control of bleeding: failure not occurring within a 24-hour interval
from hospital admission.
 Early rebleeding: failure occurring after initial control and within
the first 5 days
Results
 September 1996 to July 1999, 40 patients (out of 183 presenting with
EV bleeding) were included in the study; 25 received somatostatin
and 15 received placebo.
 Failure to control the bleeding in 3 patients; early rebleeding in 7
 Four patients died within 42 days and 10 within 1 year of admission.
Time
Bleeding to hospital admission
Adm to baseline hemodyn meas.
Endoscopy to baseline meas.
Somatostatin
6 ± 4 hours
22 ± 10 hours
18 ± 10 hours
Placebo
8 ± 3 hours
21 ± 8 hours
16 ± 7 hours
 Baseline data were similar in the 2 groups
 The HVPG was  20 mm Hg in 16 patients (64%) of somatostatin
group vs 9 patients (60%) of the placebo group.
Effects of Placebo Administration
 No effects on systemic and splanchnic hemodynamics
 Ten received a meal during placebo infusion, with significant
increase in HVPG (from 19.7 ± 3 to 20.5 ± 3 mm Hg)
 Five received a blood transfusion, with significant increase in HVPG
(20.6 ± 3 to 21.6 ± 3 mm Hg)
Effects of Somatostatin
 No significant change in mean arterial pressure
 Significant and sustained decrease in HR
 Significant and sustained reduction of HVPG, caused by a fall in
WHVP (FHVP did not change)
 The HVPG decreased  10% from the baseline value in 15 patients
(60%) in the somatostatin group and in 3 (20%) in the placebo group,
and decreased  20% of baseline in 7 (28%) in the somatostatin
group.
 16 patients received a meal: no significant change in HVPG (18.1 ±
to 18 ± 3)
 Six patients received blood transfusion: no significant change in
HVPG ( 18.7 ± 3 to 19 ± 3)
Further Bleeding vs Controlled Bleeding
 No significant difference in baseline data, except for HVPG and
WHVP, which were higher in the group with further bleeding.
Baseline HVPG  20
HVPG decreased  10% of baseline
HVPG decrease below 20 mm Hg
Further Bleeding
(10 patients)
9 (90%)
1 (10%)
2 (20%)
Controlled Bleeding
(30 patients)
16 (53%)
17 (57%)
21 (70%)
 By logistic regression analysis, both a baseline HVPG  20 mm Hg
and a decrease of HVPG  10% were independent predictors of
further bleeding.
 Only 1 of the 27 patients (67%) with a baseline HVPG  20 mm Hg
or a decrease of HVPG  10% had further bleeding, as compared
with 9 of the 13 who had neither of these 2 criteria.
 The combination of both criteria had a sensitivity of 90% and a
specificity of 87% in identifying patients with further bleeding.
Discussion
 The only study in which HVPG was continuously monitored during
variceal bleeding showed that portal pressure does not change over
the first 3 days of the acute bleeding episode (Gastroenterology
1991).
 Experimental studies have shown that gavage with blood in
portal-hypertensive rats results in significant increase of splanchnic
blood flow and portal pressure; these have also shown that blood
volume restitution after an induced hemorrhage increases portal
pressure beyond baseline value, probably as a consequence of a
raised portocollateral resistance.
 In this study, blood transfusion and ingestion of a test meal resulted
in increased HVPG in patients receiving placebo.
 There is a growing body of evidence to suggest that somatostatin is
effective in the emergency treatment of variceal bleeding; however
the effects of somatostatin on portal hemodynamics are controversial.
 The present study showed that somatostatin infusion with additional
boluses produced a significant reduction in HVPG during the course
of acute variceal bleeding.
 This may be a consequence of a vasoconstrictor response elicited by
somatostatin mainly on the splanchnic circulation, and that in turn is
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probably mediated through other pressor systems.
The effects of somatostatin have not been previously monitored
continuously in the setting of acute variceal hemorrhage.
The current study has shown that the reduction of HVPG induced by
somatostatin was sustained and even significantly enhanced.
This supports the assumption that by preventing the release of
vasoactive peptides, somatostatin may also prevent further secondary
rises in portal pressure during acute hemorrhage, such as those
induced by the presence of blood in the gut lumen.
It has been suggested that HVPG measurements during acute variceal
hemorrhage may help in identifying patients who will continue to
bleed or soon rebleed.
Despite the sensitivity of an HVPG value above 20 mm Hg in
detecting patients who will have further bleeding, its specificity is
less accurate, and approximately 50% of patients will not rebleed
even with such an HVPG.
The results is this study suggest that among patients initially at risk,
the decrease of HVPG  10% from the baseline value also
determined a significant reduction of further bleeding risk.
Monitoring or HVPG response to pharmacologic treatment may be
valuable in identifying patients at risk for further variceal bleeding.
More aggressive treatments (endoscopic therapy or TIPS) could be
reserved to those patients identified as nonresponders by HVPG
monitoring.
The decrease of HVPG was observed just a few minutes after start of
drug infusion in most cases, indicating that an early assessment may
be more suitable in clinical practice.
Conclusion
 During acute variceal bleeding, somatostatin produces a significant
and sustained reduction of HVPG and prevents secondary rises such
as those induced by blood transfusion or meals.
 Monitoring of the HVPG response to pharmacologic therapy is a
valuable method in stratifying the risk of further hemorrhage.