VARICEAL BLEEDING

AND ITS
MANAGEMENT:
FOCUS ON
TERLIPRESSIN
dr. Luciana Rotty, Sp.PD
 GASTROESOPHAGEAL VARICES

 Gatrosophageal varices are

dilated submucosal veins in
the distal esophagus or gastric
fundus caused by elevated
pressure in the portal venous
system. This condition occurs
most often in people with serious
liver diseases.

Liver
cirrhosis
PORTAL HYPERTENSION

 Normal portal vein pressure : 3-5 mmHg.

 Portal hypertension : Hepatic pressure venous gradient (HPVG)
> 5mmHg.
 If portal pressure remains higher than inferior vena caval
pressure for a significant period, venous collaterals develops.
 The most dangerous collaterals occur in the distal esophagus
and gastric fundus, known as varices.
 SITES OF PORTAL HYPERTENSION

Cause of PH :
1. Increased intrahepatic
resistance
2. Changes in portal flow

Sleisenger and Fordtrant’s Gastrointestinal and Liver diaseas Textbook, 10th ed, 2015.
ENDOSCOPIC VIEW

Normal distal esophagus Varices esophagus with prominent

cherry-red spots
 EPIDEMIOLOGY VARICES

 The incidence of varices in cirrhotic patients is around 5% at

the end of one year and 28% at the end of three years.
 Small varices progress to large varices at a rate of 10% to 12%
annually.
 Approximately 50% of all patients with a new diagnosis of
cirrhosis have gastrointestinal varices.
 Annual risk of variceal bleeding among small and large varices is
5% and 15% respectively.
 The six-week mortality rate among patients with index variceal
bleeding is approximately 20%.
 Risk of rebleeding without endoscopic intervention is almost
60% with an increased mortality rate (33%)

Kovalak M. Endoscopic screening for varices in cirrhotic patients: data from a national endoscopic database. Gastrointest Endosc. 2007 Jan;65(1):82-8.
 VARICES PREVALENCE IN
CIRRHOTIC PATIENTS
Prevalence of varices
increases with the severity of
liver disease (Cirrhosis
decompensated)
Child-Pugh:
class A 42.7%
class B 70.7%
class C 75.5%

Kovalak M. Endoscopic screening for varices in cirrhotic patients: data from a national endoscopic database. Gastrointest Endosc. 2007 Jan;65(1):82-8.
 ACUTE VARICEAL BLEEDING
MORTALITY WITHIN 6-WEEKS
178 cirrhosis patients with acute
variceal bleeding →
16% patients died
within 6-weeks of
index bleed.

70 cirrhosis patients with acute

variceal bleeding →
26% patients died
within 6-weeks of
index bleed.
Reverter E, et al. A MELD-based model to determine risk of mortality among patients with acute variceal bleeding. Gastroenterology. 2014 Feb;146(2):412-19.e3.
Fortune BE, et al. Child-Turcotte-Pugh Class is Best at Stratifying Risk in Variceal Hemorrhage: Analysis of a US Multicenter Prospective Study. J Clin Gastroenterol. 2017 May/Jun;51(5):446-453.
 LIVER CIRRHOSIS

 Liver Cirrhosis is a liver disorder characterized by diffuse

fibrosis and regenerative nodule formation in liver

Lead to architectural
distortion & functional
impairment

Theise, N. Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach. Mod Pathol 20, S3–S14 (2007). https://doi.org/10.1038/modpathol.3800693
 LIVER CIRRHOSIS
COMPLICATIONS Esophageal Varices
Gastric Varices

Hepatorenal
Portal Syndrome (HRS)
Ascites
Hypertension
Spontaneous
Liver Bacterial
Cirrhosis Peritonitis (SBP)

Liver Hepatic
Insufficiency Encephalopathy

Icteric

D'Amico G,, et alL. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006 Jan;44(1):217-31..
 DEVELOPMENT OF CIRRHOSIS
COMPLICATIONS

Dohler KD, Meyer M. Vasopressin analogues in the treatment of hepatorenal syndrome and gastrointestinal haemorrhage. Best Pract Res Clin Anaesthesiol. 2008 Jun;22(2):335-50.
 SIGNS AND SYMPTOMS

 Gastroesophageal varices usually don't cause signs

and symptoms unless they bleed.
 Signs and symptoms of bleeding esophageal varices
include:
 Vomiting large amounts of blood
 Black, tarry or bloody stools
 Lightheadedness
 Loss of consciousness in severe cases
 GASTROESOPHAGEAL VARICES (VARICEAL HEMORRHAGE)
Acute variceal • Admitted to the ICU.
hemorrhage • Hemoglobin should be maintained around 7 g/dL.

From Cross Sectional Study

Primary Prophylaxis
THE ABSENCE OF A PRIOR VARICEAL BLEED
non-selective beta-blocker is recommended in patients with small varices (< 5 mm) who also present
with criteria for increased risk of bleeding (Child B/C and red wale sign).

PATIENTS WITH SMALL VARICES AND NO CRITERIA FOR INCREASED HEMORRHAGE

non-selective beta blockers can be used, but their effectiveness is yet to be established.

In patients with medium to large varices, both beta blockers and endoscopic variceal ligation (EVL) can
be used.
 PREDICTING ESOPHAGEAL VARICES
USING FIBROSCAN AND PLATELET COUNT
Endoscopy
 ACUTE VARICEAL BLEEDING
TREATMENT
 Emergency situation
 Resuscitation (ABC):
1. Protect airway
2. Consider fluid Resuscitation
3. Consider blood transfusion is indicated
 Prophylaxis antibiotic

 Vasoactive agent
 Endoscopy

Garcia-Tsao G, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017
Jan;65(1):310-335.
 ACUTE VARICEAL BLEEDING
TREATMENT TARGET

Prevent 6-week mortality

Bleeding control
after treatment

Reduce bleeding
recurrence at 5 days
or mortality

Garcia-Tsao G, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017
Jan;65(1):310-335.
 EFFECT OF
VASOACTIVE
TREATMENT TO
OVERALL 7-DAYS
MORTALITY
 The use of vasoactive agents was
associated with a significantly
lower risk of acute 7-day
mortality, and a significant
improvement in haemostasis,
lower transfusion requirements,
and a shorter hospital stay.
 Current guidelines recommend
vasoactive agents should be
initiated as soon as variceal
haemorrhage is suspected and
an EGD, performed with 12h with
either oesophageal variceal
ligation or sclerotherapy.
Wells M, et al. Meta-analysis: vasoactive medications for the management of acute variceal bleeds. Aliment Pharmacol Ther. 2012 Jun;35(11):1267-78.
APASL
RECOMMENDATION
(2011)
 RECOMMENDED DOSE AND DURATION
OF VASOACTIVE AGENTS IN ACUTE
VARICES BLEEDING TREATMENT

Garcia-Tsao G, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017
Jan;65(1):310-335.
 TERLIPRESSIN
Aminoacid composition of Terlipressin ✓an analogue of vasopressin
✓half-life of 6h
✓effect occurs via vascular V1
receptors and renal tubular V2
receptors
✓has recently been shown to be
effective in patients with
hepatorenal syndrome (HRS) or in
catecholamine-resistant septic
shock.

Sites of activity and molecular properties of Terlipressin

Saner FH, et al. Pharmacology, clinical efficacy and safety of terlipressin in esophageal varices bleeding, septic shock and hepatorenal syndrome. Expert Rev Gastroenterol Hepatol. 2007 Dec;1(2):207-17.
 EFFECTS OF TERLIPRESSIN TO
BLOOD CIRCULATION

PORTAL TENSION 

SPLANCHNIC CIRCULATION


COLLATERAL FLOW 

VARICEAL TENSION 

Dohler KD, Meyer M. Vasopressin analogues in the treatment of hepatorenal syndrome and gastrointestinal haemorrhage. Best Pract Res Clin Anaesthesiol. 2008 Jun;22(2):335-50.
 VARICEAL PRESSURE COURSE AFTER START OF
TERLIPRESSIN VS. PLACEBO

 The infusion of terlipressin in

cirrhotic patients decreases
varical pressure in a range
between 5-35%.
 The higher the variceal pressure
the better the terlipressin
effect.

Saner FH, et al. Pharmacology, clinical efficacy and safety of terlipressin in esophageal varices bleeding, septic shock and hepatorenal syndrome. Expert Rev Gastroenterol Hepatol. 2007 Dec;1(2):207-17.
 TERLIPRESSIN VS. PLACEBO

Compared with no vasoactive drug, terlipressin significantly improved the control

of bleeding within 48 hours (OR=2.94, P=.0008) and
decreased the in-hospital mortality (OR=0.31, P=.008).
Zhou X, et al. Medicine (Baltimore). 2018;97(48):1-11. https://doi.org/10.1097/md.0000000000013437
 EFFICACY AND
SAFETY OF
TERLIPRESSIN

Krag, A., Borup, T., Møller, S. et al. Adv Therapy 25, 1105 (2008). https://doi.org/10.1007/s12325-008-0118-7
 ECONOMIC EVALUATION OF
TERLIPRESSIN IN VARICEAL BLEEDING

Wechowski J. Curr Med Res Opin . 2007;23(7):1481-91. https://doi.org/10.1185/030079907X199736

THANK YOU
 PRODUCT PROFILE TERLIPIN
Composition:
Terlipressin acetate 1 mg equivalent to terlipressin 0.86 mg
Indication:
Treatment of bleeding esophageal varices.
Dossage form:
Dry powder for injection
Dossage:
➢ Adults
 Initially, an intravenous (IV) injection of 2 mg terlipressin is given every 4 hours.
 The treatment should be maintained until bleeding has been controlled for 24 hours, but up to a maximum of 48 hours.
 After the initial dose, the dose can be adjusted to 1 mg i.v. every 4 hours in patients with body weight <50 kg or if adverse
effects occur.
➢ Children and elderly
 No data are available regarding dosage recommendation in these patient populations.
Administration:
 Dissolve 1 mg powder for injection in 5 ml 0.9% NaCl injection.
 Terlipressin is administered by slow i.v. injection (over 1 minute).
 After reconstitution with 0.9% NaCl injection, solution stable for 12 hours at temperature 25oC.
 Terlipressin is only to be used under continuous monitoring of cardiovascular function (e.g. blood pressure, heart rate and
fluid balance) using intensive medical units.
Presentation:
Box, 1 vial @ 1 mg