Acute Variceal Hemorrhage - Treatment

Acute Variceal Hemorrhage - Treatment
Overview and Recommendations
Background
● Acute variceal hemorrhage usually arises from gastroesophageal varices, which are collateral porto-
systemic vascular channels formed in response to portal hypertension, which is often caused by
cirrhosis of the liver.
● Excess pressure and volume distention of esophageal and/or gastric veins results in a compromise to
the vessel wall with attendant internal gastrointestinal bleeding, often severe and life-threatening.
Evaluation and management
● Admit patients with suspected acute variceal hemorrhage to the intensive care unit.
● Provide prompt intravascular volume support and blood transfusions as needed, being careful to
maintain hemoglobin between 7 g/dL (70 g/L) and 9 g/dL (90 g/L), but avoiding excessive transfusion
that can result in increased rates of rebleeding and increased mortality.
● Start pharmacologic therapy as soon as variceal hemorrhage is suspected and continue for up to 5
days after con rmation of the diagnosis (Strong recommendation). Options include:
⚬ terlipressin
⚬ somatostatin
⚬ somatostatin analog (octreotide, vapreotide)
● Start short-term antibiotic prophylaxis (maximum 7 days) in any patient with cirrhosis and
gastrointestinal hemorrhage (Strong recommendation).
⚬ Recommended antibiotic is ceftriaxone 1 g/day IV, especially for patients with advanced cirrhosis,
patients on quinolone prophylaxis, and in hospitals with high prevalence of quinolone-resistant
organisms.
● Perform esophagogastroduodenoscopy (EGD) within 12 hours to diagnose and treat variceal

hemorrhages with endoscopic variceal ligation or sclerotherapy (Strong recommendation).
● Transjugular intrahepatic portosystemic shunt (TIPS) is indicated if esophageal variceal bleeding

cannot be controlled or recurs despite pharmacologic and endoscopic therapy.
● Balloon tamponade should be used temporarily (≤ 24 hours) for uncontrollable bleeding until more
de nitive therapy (TIPS or endoscopic therapy) can be performed.
● In patients who bleed from gastric fundal varices:
⚬ Endoscopic variceal obturation using tissue adhesives such as cyanoacrylate is preferred, but
endoscopic variceal ligation is an option if endoscopic variceal obturation is not available.
⚬ Perform a TIPS procedure if bleeding cannot be controlled or recurs despite pharmacologic and
endoscopic therapy.
Related Summaries
● Acute Variceal Hemorrhage

● Esophageal Varices
● Esophageal Variceal Hemorrhage - Primary Prophylaxis
● Esophageal Variceal Hemorrhage - Prevention of Rebleeding
● Gastric Varices
● Portal Hypertension
Recommendations from Professional Organizations
Baveno
● Baveno VI 2015 international workshop consensus recommendations on treatment of acute variceal
bleeding 3
⚬ blood volume restitution should be conservative (Baveno Level 1b, Grade A)
– goal of resuscitation is to preserve tissue perfusion; volume restitution should be given to

maintain hemodynamic stability
– packed red blood cell transfusion should be administered to maintain hemoglobin level 7-8 g/dL
(70-80 g/L), but consider other factors, such as
● comorbidities
● patient age
● hemodynamic status
● ongoing bleeding
⚬ insu cient evidence for recommendation about management of coagulopathy and

thrombocytopenia (Baveno Level 5, Grade D)
⚬ prothrombin time/INR not reliable indicator of coagulation status in patients with cirrhosis (Baveno
Level 1b, Grade A)
⚬ vasoactive drugs (octreotide, somatostatin, terlipressin, vapreotide)
– start as soon as possible before diagnostic endoscopy in patients with suspected variceal
bleeding (Baveno Level 1b, Grade A)
– use in conjunction with endoscopic therapy and continue for up to 5 days (Baveno Level 1a,
Grade A)
– monitor sodium levels in patients receiving terlipressin as hyponatremia has been reported
with terlipressin use (especially in patients with preserved liver function) (Baveno Level 1b,
Grade A)
⚬ prophylactic antibiotics should be started at time of admission (Baveno Level 1a, Grade A)
– consider individual patient risks and local antimicrobial susceptibility patterns to determine
appropriate rst line antibiotic for prophylaxis at each treatment center (Baveno Level 5, Grade
D)
– consider IV ceftriaxone 1g/24 hours in
● patients with advanced cirrhosis (Baveno Level 1b, Grade A)

● hospitals with high prevalence of quinolone-resistant bacterial infections (Baveno Level 5,
Grade D)
● patients on previous quinolone prophylaxis (Baveno Level 5, Grade D)
– patients with Child-Pugh class A cirrhosis have very low risk of bacterial infection and mortality
(Baveno Level 2b, Grade B), but insu cient evidence to determine if antibiotic prophylaxis can
be avoided in this group
⚬ recommendations for management and prevention of hepatic encephalopathy in patients with
cirrhosis and upper GI bleeding are limited
– lactulose or rifaximin may prevent hepatic encephalopathy (Baveno Level 1b, Grade A), but
further evidence on risk/bene t ratio and identi cation of high-risk patients are needed before
formal recommendations are made (Baveno Level 5, Grade D)
– treat patients with acute variceal bleeding and episodic hepatic encephalopathy with lactulose
25 mL every 12 hours until 2-3 soft bowl movement produced, then titrate dose to maintain 2-3
soft bowel movements each day (Baveno Level 5, Grade D)
⚬ perform esophagogastroduodenoscopy after hemodynamic resuscitation and within 12 hours of
admission for patients with gastrointestinal (GI) bleeding and features suggesting cirrhosis (Baveno
Level 5, Grade D)
⚬ endoscopic therapy
– consider placing patients with acute variceal hemorrhage in intensive care units or other well
monitored units (Baveno Level 5, Grade D)
– GI endoscopist experienced with endoscopic hemostasis and support sta with expertise in
endoscopic device usage on-call to enable performance of endoscopy at any time
recommended (Baveno Level 5, Grade D)
– perform endoscopy with airway protection for patients with altered consciousness (Baveno
Level 5, Grade D)
– consider pre-endoscopy erythromycin infusion (250 mg IV 30-120 minutes before endoscopy) in
patients without contraindications (such as QT prolongation) (Baveno Level 1b, Grade A)
– for patients with acute esophageal variceal bleeding, ligation is recommended (Baveno Level 1b,
Grade A)
– endoscopic therapy with tissue adhesive (such as N-butyl-cyanoacrylate) is recommended for
● acute bleeding from isolated gastric varices (Baveno Level 1b, Grade A)
● gastroesophageal varices type 2 that extend beyond the cardia (Baveno Level 5, Grade D)
– in bleeding from gastroesophageal varices type 1, esophageal variceal ligation (EVL) or tissue
adhesive can be used (Baveno Level 5, Grade D)
– consider additional glue injection (2-4 weeks after initial treatment), beta-blocker therapy, both
glue injection and beta-blocker therapy, or transjugular intrahepatic portosystemic shunt (TIPS)
for prevention of rebleeding (Baveno Level 5, Grade D)
⚬ strongly consider transjugular intrahepatic portosystemic shunt (TIPS) placement early in patients
with esophageal varices, gastroesophageal varices type 1, or gastroesophageal varices type 2 who
are at high risk of treatment failure (Baveno Level 1b, Grade A)
– treat within 72 hours (ideally within 24 hours) after initial pharmacological and endoscopic
therapy
– high risk of treatment failure de ned as Child-Pugh Class C (< 14 points) or Child-Pugh Class B
with active bleeding
⚬ balloon tamponade (Baveno Level 5, Grade D)
– associated with high incidence of severe adverse events

– reserve for cases of refractory esophageal bleeding
– use temporarily (maximum 24 hours) until de nitive treatment can be started
– provide intensive care unit monitoring
⚬ self-expanding covered esophageal metal stents may be as e ective as and safer than balloon
tamponade for refractory esophageal variceal bleeding (Baveno Level 4, Grade C)
⚬ failure to control bleeding de ned as death or need to change therapy due to any of
– fresh hematemesis or nasogastric aspiration of ≥ 100 mL of fresh blood ≥ 2 hours after start of
speci c drug therapy or therapeutic endoscopy
– hypovolemic shock
– drop in hemoglobin ≥ 3 g/dL (30 g/L) (or drop in hematocrit ≥ 9%) within any 24-hour period (if
no transfusion)
⚬ management of treatment failure
– persistent bleeding despite combined pharmacologic and endoscopic therapy is best managed
by TIPS with polytetra uoroethylene (PTFE)-covered stents (Baveno Level 2b, Grade B)
– if rebleeding during rst 5 days, consider second attempt at endoscopic therapy; if severe
rebleeding, PTFE-covered TIPS is likely best option (Baveno Level 2b, Grade B)
⚬ prognostic considerations
– factors most consistently found to predict 6-week mortality (Baveno Level 2b, Grade B)
● Child-Pugh Class C
● Model of End Stage Liver Disease (MELD) score ≥ 18
● failure to control bleeding or early rebleeding
American Association for the Study of Liver Diseases (AASLD)
● AASLD 2016 guidance for risk strati cation, diagnosis, and management of portal hypertension and
acute variceal hemorrhage 1

⚬ admit patients with suspected acute variceal hemorrhage to intensive care unit
⚬ provide prompt intravascular volume support and administer conservative blood transfusions as
needed, starting transfusion when hemoglobin reaches about 7 g/dL (70 g/L) and maintaining
hemoglobin between 7 g/dL (70 g/L) and 9 g/dL (90 g/L)
⚬ start IV vasoactive pharmacologic therapy as soon as variceal hemorrhage suspected and prior to
esophagogastroduodenoscopy (EGD)
Table 1. American Association for the Study of Liver Diseases (AASLD) Dosing
Recommendations
Drug Recommended Dose Duration of Therapy
Octreotide 50 mcg IV bolus 2-5 days

(somatostatin analog) (consider repeating in
rst hour if bleeding
persists), then
continuous infusion 50
mcg/hour
Vasopressin – Continuous IV 24 hours

infusion 0.2-0.4
units/minute
(maximum 0.8
units/minute)
– Accompany with IV
nitroglycerin initial
dose 40 mcg/minute
(maximum 400
mcg/minute)
adjusted to maintain
systolic blood
pressure > 90 mm Hg
Somatostatin 250 mcg IV bolus 2-5 days

(consider repeating in
persists), then
continuous infusion
250-500 mcg/hour
Terlipressin – Initial dose for 48 2-5 days

(vasopressin analog) hours: 2 mg IV every
4 hours until bleeding
controlled
– Maintenance dose: 1
mg IV every 4 hours
to prevent rebleeding
⚬ start short-term antibiotic prophylaxis (maximum 7 days) concurrent with vasoactive therapy in
any patient with cirrhosis and gastrointestinal hemorrhage
– ceftriaxone 1 g/day IV is preferred, especially for patients with advanced cirrhosis, patients on
quinolone prophylaxis, and in hospitals with high prevalence of quinolone-resistant organisms
– consider discontinuing antibiotics if bleeding resolves and vasoactive therapy has ceased
⚬ perform esophagogastroduodenoscopy (EGD) within 12 hours of admission (in hemodynamically

stable patients) to diagnose and treat variceal hemorrhages with endoscopic variceal ligation (EVL)
or sclerotherapy
⚬ perform EVL if variceal source con rmed or suspected
⚬ transjugular intrahepatic portosystemic shunt (TIPS)
– consider ≤ 72 hours after EGD/EVL in patients with high risk of failure or rebleeding (Child-
Turcotte-Pugh class C or Child-Turcotte-Pugh class B with bleeding on endoscopy)
– indicated if esophageal variceal bleeding cannot be controlled or recurs despite pharmacologic
and endoscopic therapy
– in patients with successful TIPS, discontinue IV vasoactive therapy
⚬ in patients without early TIPS
– continue IV vasoactive therapy for 2 -5 days

– begin nonselective beta blockers (NNSB) once vasoactive therapy is discontinued
– utilize rescue TIPS in patients with uncontrolled bleeding or bleeding recurrence after EVL and
vasoactive therapy
⚬ in patients who bleed from gastric varices
– EVL (when feasible in select patients) or endoscopic variceal obturation using cyanoacrylate
adhesive recommended for patients with gastroesophageal varices type 1 (GOV 1)
– TIPS is recommended treatment for patients with cardiofundal varices (GOV 2 or IGV 1)
● Child-Pugh or Child-Turcotte-Pugh (CTP) score uses presence of ascites and encephalopathy, albumin
and bilirubin levels, and prothrombin time or INR to grade severity of liver disease
⚬ see DynaMed calculators for
– Child-Pugh-Turcotte Classi cation for Severity of Liver Disease

– Child-Pugh Classi cation for Severity of Liver Disease (SI units)
National Institute for Health and Care Excellence (NICE)
● NICE 2016 guidance for managing complications in patients with cirrhosis
⚬ in patients with upper gastrointestinal bleeding and cirrhosis, o er prophylactic antibiotics IV

⚬ use NICE guidance on antimicrobial stewardship: systems and processes for e ective antimicrobial
medicine to guide antimicrobial use (NICE 2015 Aug:NG15 PDF )
⚬ Reference - Cirrhosis in over 16s: assessment and management. (NICE 2016 Jul:NG50 PDF )
Intensive Care
● admit to intensive care 1 , 2
● assess for cirrhosis via 2
⚬ patient history or clinical data including physical exam ndings/stigmata of liver disease
⚬ laboratory tests showing thrombocytopenia, altered coagulation, and abnormal liver tests
● assess and protect airway as needed 1 , 2
⚬ no strong data supporting prophylactic endotracheal intubation

⚬ endotracheal intubation indicated if
– ongoing hematemesis
– continued hemodynamic instability after volume loading
– altered mental status or agitation with absence of cooperation during exam
– Glasgow Coma Scale < 8
● obtain peripheral venous access and consider venous central line placement 2
● provide cautious hemodynamic resuscitation to avoid rebound increase in portal pressure or early
rebleeding
⚬ provide prompt intravascular volume support and conservative blood transfusions as needed,
starting transfusion when hemoglobin reaches about 7 g/dL (70 g/L) and maintaining hemoglobin
between 7 g/dL (70 g/L) and 9 g/dL (90 g/L) 1
⚬ volume may be replaced with crystalloids and packed red cells (Ann Am Thorac Soc 2015
Jul;12(7):1100 )
⚬ avoid vigorous use of saline which may induce ascites or uid at other extravascular sites
(Hepatology 2007 Sep;46(3):922 )
⚬ blood volume restitution should be conservative (Baveno Level 1b, Grade A) 3
– goal of resuscitation is to preserve tissue perfusion; volume restitution should be given to

maintain hemodynamic stability
– packed red blood cell transfusion should be administered to maintain hemoglobin level 7-9 g/dL
(70-90 g/L) but consider other factors, such as
● comorbidities
● patient age
● hemodynamic status
● ongoing bleeding
⚬ restrictive blood transfusion associated with reduced bleeding and rebleeding, reduced
complications, and increased survival 2
● management of coagulopathy and thrombocytopenia
⚬ insu cient evidence for recommendation about management of coagulopathy and

thrombocytopenia (Baveno Level 5, Grade D) 3
⚬ overtransfusion of fresh frozen plasma and platelets may increase portal pressure and risk of
continued bleeding or rebleeding 2

⚬ prothrombin time/INR not reliable indicator of coagulation status in patients with cirrhosis (Baveno
Level 1b, Grade A) 3
● provide antibiotic prophylaxis to reduce bacterial infections, early rebleeding, and mortality 1 , 2 , 3
⚬ consider individual patient risks and local antimicrobial susceptibility patterns to determine
appropriate rst line antibiotic for prophylaxis at each treatment center (Baveno Level 5, Grade D)
⚬ ceftriaxone 1 g/day IV may be considered in certain patient populations ( Baveno Level 1b, Grade A)
● beta blockers should not be used during acute variceal bleeding episodes (Hepatology 2007
Sep;46(3):922 )
● additional support may include
⚬ renal support by maintaining urine output > 50 mL/hour

⚬ metabolic support
– monitor blood glucose

– monitor and treat for delirium tremens, electrolyte disturbances
– inject thiamine if indicated
⚬ monitoring mental state and avoiding sedation

⚬ Reference - Med Clin North Am 2008 May;92(3):551
Medications
Vasoactive drugs
Clinical role
● vasoactive drugs cause splanchnic vasoconstriction, reducing portal venous in ow and resulting in
reduced portal pressure and variceal bleeding 1 , 2
● start vasoactive drugs as soon as variceal hemorrhage suspected ( Baveno Level 1b, Grade A) 1 2 , 3
⚬ ideally during transport or on admission

⚬ as soon as possible before diagnostic endoscopy
● additional recommendations for vasoactive drugs
⚬ American Association for the Study of Liver Diseases (AASLD) 2016 guidance for risk strati cation,
diagnosis, and management of portal hypertension and acute variceal hemorrhage 1

– start IV vasoactive pharmacologic therapy as soon as variceal hemorrhage suspected and prior
to esophagogastroduodenoscopy (EGD)
Table 2. American Association for the Study of Liver Diseases (AASLD) Dos-
ing Recommendations
Octreotide 50 mcg IV bolus 2-5 days

(somatostatin analog) (consider repeating in
persists), then
continuous infusion 50
mcg/hour
Vasopressin ● Continuous IV 24 hours

infusion 0.2-0.4
units/minute
(maximum 0.8
units/minute)
● Accompany with IV
nitroglycerin initial
dose 40 mcg/minute
(maximum 400
mcg/minute)
adjusted to maintain
systolic blood
pressure > 90 mm
Hg
Somatostatin 250 mcg IV bolus 2-5 days

(consider repeating in
persists), then
continuous infusion
250-500 mcg/hour
Terlipressin ● Initial dose for 48 2-5 days

(vasopressin analog - hours: 2 mg IV every
not available in the 4 hours until
United States) bleeding controlled
● Maintenance dose: 1
mg IV every 4 hours
to prevent
rebleeding
⚬ Baveno VI international workshop consensus recommendations 3
– vasoactive drugs options include octreotide, somatostatin, terlipressin, and vapreotide

(somatostatin, terlipressin, and vapreotide not available in the United States
– use in conjunction with endoscopic therapy and continue for up to 5 days (Baveno Level 1a,
Grade A)
– if using terlipressin, monitor patient sodium levels due to risk of hyponatremia (Baveno Level
1b, Grade A)
STUDY
● SUMMARY
vasoactive drugs may decrease mortality and improve hemostasis in patients with acute variceal
hemorrhage DynaMed Level 2
SYSTEMATIC REVIEW: Aliment Pharmacol Ther 2012 Jun;35(11):1267 | Full Text
Details
⚬ based on systematic review with trial-speci c quality measures not reported
⚬ systematic review of 30 randomized trials comparing vasoactive drugs to control (placebo or usual
care) in 3,111 patients with acute variceal bleeding
⚬ vasoactive drugs included octreotide, somatostatin, vasopressin, terlipressin, and vapreotide
⚬ drug dosing regimens varied across trials
⚬ vasoactive drugs associated with reduced risk of 7-day mortality (risk ratio [RR] 0.74, 95% CI 0.57-
0.95) in analysis of 19 trials
⚬ no individual vasoactive drug associated with reduced mortality compared to control
⚬ vasoactive drugs associated with improved hemostasis compared to control
– overall (RR 1.21, 95% CI 1.13-1.3) in analysis of 24 trials with 1,732 patients
– with octreotide (RR 1.2, 95% CI 1.12-1.27) in analysis of 11 trials with 932 patients
– with terlipressin (RR 1.39, 95% CI 1.18-1.63) in analysis of 7 trials with 443 patients
– with vapreotide (RR 1.33, 95% CI 1.04-1.69) in 1 trial with 196 patients
⚬ no signi cant di erence in hemostasis comparing control to
– somatostatin in analysis of 3 trials with 179 patients, results limited by signi cant heterogeneity
– vasopressin in analysis of 3 trials with 82 patients
⚬ Reference - Aliment Pharmacol Ther 2012 Jun;35(11):1267 full-text
Vasopressin
● vasopressin (Pitressin) is exogenous antidiuretic hormone (ADH) not FDA approved for use in acute
gastrointestinal hemorrhage
● clinical use limited by multiple side e ects including
⚬ cardiac and peripheral ischemia

⚬ arrhythmias
⚬ hypertension
⚬ bowel ischemia
⚬ Reference - Hepatology 2007 Sep;46(3):922
● to minimize side e ects, limit continual use at highest e ective dose to ≤ 24 hours and administer
with nitroglycerin 1
● combined use of vasopressin plus nitroglycerin reduces adverse events, but other vasoactive
mediations including terlipressin, somatostatin, and somatostatin analogues have lower rates of
adverse events than combination vasopressin plus nitroglycerin (Gastrointest Endosc Clin N Am 2015
Jul;25(3):479 )
● dosing 1
⚬ continuous vasopressin IV 0.2-0.4 units/minute (maximum 0.8 units/minute) for 24 hours

⚬ nitroglycerin IV
– initial dose 40 mcg/minute (maximum 400 mcg/minute)

– adjust to maintain systolic blood pressure > 90 mm Hg
STUDY
● SUMMARY
addition of nitroglycerin to vasopressin may increase control of acute variceal hemorrhage with
fewer cardiac complications DynaMed Level 2
RANDOMIZED TRIAL: Hepatology 1986 May-Jun;6(3):410
Details
⚬ based on randomized trial with allocation concealment not stated
⚬ 62 patients with acute variceal bleeding and signs of continuing hemorrhage were randomized to
vasopressin plus nitroglycerin vs. vasopressin alone for 12-hour infusion period
– vasopressin - initial IV bolus 20 units over 15 minutes, then continuous infusion 0.4 units/minute
– nitroglycerin - initial dose 40 mcg/minute IV, increased by 40 mcg/minute every 15 minutes if
systolic blood pressure > 100 mm Hg (maximum 400 mcg/minute)
⚬ 10 patients had ≥ 1 variceal bleeding episode treated during trial with each episode ≥ 14 days after
previous episode
⚬ 72 bleeding episodes were included in analysis
⚬ comparing vasopressin plus nitroglycerin vs. vasopressin alone
– hemorrhage controlled in 68% vs. 44% of episodes (p < 0.05, NNT 5)

– complications requiring discontinuation of treatment (left ventricular failure, severe angina
pectoris, bradycardia) in 3% vs. 23% of patients (p < 0.02, NNT 5)
– admission mortality 29% vs. 30% (not signi cant)
⚬ Reference - Hepatology 1986 May-Jun;6(3):410
● see also Vasopressin
Terlipressin
● terlipressin is synthetic analogue of vasopressin not currently available in United States 2
● terlipressin has longer biologic activity and fewer side e ects than vasopressin 2
● dosing 1 , 2
⚬ initial dose 2 mg IV every 4 hours for 48 hours

⚬ may decrease to 1 mg IV every 4 hours once bleeding controlled and continue for up to 5 days to
prevent rebleeding
● monitor patient sodium levels during use due to risk of hyponatremia (Baveno Level 1b, Grade A) 3
● abdominal pain most common side e ect (Gastrointest Endosc Clin N Am 2015 Jul;25(3):479 )
● may cause ischemic complications and dysrhythmias in patients with ischemic heart disease or
peripheral vascular disease 2
STUDY
● SUMMARY
terlipressin may improve in-hospital mortality and bleeding control within 48 hours compared
to no vasoactive therapy in patients with acute variceal hemorrhage and cirrhosis
DynaMed Level 2
SYSTEMATIC REVIEW: Medicine (Baltimore) 2018 Nov;97(48):e13437 | Full Text
Details
⚬ based on systematic review with methodologic limitations
⚬ systematic review of 30 randomized trials evaluating terlipressin therapy in 3,344 patients with
acute variceal hemorrhage and cirrhosis
⚬ all trials had ≥ 1 limitation including
– unclear or inadequate allocation concealment

– lack of or unclear blinding
– small sample size
⚬ compared to no vasoactive therapy, terlipressin associated with
– improved bleeding control within 48 hours in analysis of 4 trials with 225 patients
● odds ratio [OR] 2.94 (95% CI 1.57-5.51)

● NNT 3-9 with bleeding control within 48 hours in 52% of control group
– decreased in-hospital mortality in analysis of 3 trials with 141 patients
● OR 0.31 (95% CI 0.13-0.73)

● NNT 4-16 with in-hospital mortality in 33% of control group
⚬ compared to somatostatin, terlipressin associated with increased risk of complications in analysis

of 4 trials with 822 patients
– OR 2.44 (95% CI 1.03-5.8)
– NNH 4-454 with complications in 8% of control group
⚬ compared to octreotide, terlipressin associated with decreased bleeding control ≤ 24 hours in

analysis of 2 trials with 147 patients
– OR 0.37 (95% CI 0.18-0.76)
– NNH 2-19 with bleeding control ≤ 24 hours in 78% of control group
⚬ Reference - Medicine (Baltimore) 2018 Nov;97(48):e13437 full-text
STUDY
● SUMMARY
terlipressin may reduce mortality and risk of failing initial hemostasis in patients with cirrhosis
and suspected or documented esophageal variceal bleed DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2003;(1):CD002147
Details
⚬ based on Cochrane review with trial-speci c quality measures not reported
⚬ systematic review of 20 randomized trials evaluating terlipressin in 1,609 patients with cirrhosis
and suspected or documented bleeding from esophageal varices
⚬ comparing terlipressin to placebo, terlipressin associated with reduced
– all-cause mortality (risk ratio 0.66, 95% CI 0.49-0.88) in analysis of 7 trials with 443 patients
– risk of failing initial hemostasis (odds ratio [OR] 0.47, 95% CI 0.32-0.7) in analysis of 7 trials with
443 patients
– number of procedures needed to control bleeding (OR 0.58, 95% CI 0.38-0.88) in analysis of 4
trials with 196 patients
⚬ comparing octreotide to terlipressin, terlipressin associated with
– increased risk of failing initial hemostasis (OR 1.97, 95% CI 1.08-3.59) in analysis of 3 trials with
141 patients
– no signi cant di erences in all-cause mortality or number of procedures needed to control
bleeding
⚬ no signi cant di erences comparing terlipressin to
– somatostatin in analysis of 3 trials with 302 patients

– vasopressin in analysis of 5 trials with 301 patients
– balloon tamponade in analysis of 3 trials with 141 patients
– endoscopic treatment in 1 trial with 219 patients
⚬ Reference - Cochrane Database Syst Rev 2003;(1):CD002147
STUDY
● SUMMARY
terlipressin and somatostatin appear to have similar 30-day mortality in patients with cirrhosis
and esophageal variceal bleeding DynaMed Level 2
COHORT STUDY: Eur J Gastroenterol Hepatol 2016 Nov;28(11):1275 | Full Text
Details
⚬ based on retrospective cohort study
⚬ 2,324 patients with cirrhosis and esophageal variceal bleeding treated with terlipressin or
somatostatin were included
⚬ propensity score calculated based on age, sex, alcohol-related disorders, hepatocellular carcinoma,
ascites, hepatic encephalopathy, renal functional impairment, and bacterial infection
⚬ no signi cant di erence in risk of 30-day mortality comparing terlipressin and somatostatin
⚬ Reference - Eur J Gastroenterol Hepatol 2016 Nov;28(11):1275 full-text
STUDY
● SUMMARY
72 hours of terlipressin does not further reduce bleeding or mortality compared to 24 hours of
terlipressin in patients with acute esophageal variceal bleeding and successful variceal band
ligation DynaMed Level 1
RANDOMIZED TRIAL: J Hepatol 2012 Apr;56(4):819
Details
⚬ based on randomized trial
⚬ 130 patients (mean age 50 years, 75% male) with cirrhosis and acute esophageal variceal bleeding
having endoscopic variceal band ligation and terlipressin for 24 hours were randomized to
terlipressin 1 mg every 6 hours vs. placebo for additional 48 hours
⚬ patients were excluded for high risk of rebleeding de ned as failure to control bleeding with
endoscopic variceal band ligation; bleeding disorders; known hepatocellular carcinoma, other
hepatic metastatic malignancy, or portal vein thrombosis; advanced cirrhosis (Child-Pugh score ≥
12); and sepsis or multiorgan failure requiring continuous ionotropic or ventilatory support after
uid and blood product resuscitation
⚬ comparing additional terlipressin vs. placebo
– failure to control bleeding at day 5 in 1.5% vs. 0% (not signi cant)

– 30-day rebleeding in 1.5% vs. 3.1% (not signi cant)
– 30-day mortality 9.2% vs. 9.2% (not signi cant)
⚬ Reference - J Hepatol 2012 Apr;56(4):819
STUDY
● SUMMARY
continuous terlipressin administration may be associated with decreased treatment failure in
patients with acute variceal bleeding and portal hypertension DynaMed Level 2
RANDOMIZED TRIAL: Indian J Gastroenterol 2018 Jul;37(4):313
Details
⚬ based on randomized trial without blinding
⚬ 86 consecutive patients with acute variceal bleeding and portal hypertension were randomized to 1
of 2 methods for delivery of terlipressin for 5 days
– terlipressin 1 mg IV followed by continuous infusion of 4 mg over 24 hours
– terlipressin 2 mg Iv follower by 1 mg IV injection every 6 hours
⚬ treatment failure de ned as 1 of the following
– fresh hematemesis or nasogastric aspiration of > 100 mL of fresh blood ≥ 2 hours after
therapeutic endoscopy
– ≥ 3 g/dL drop in hemoglobin level without transfusion given
– death
⚬ comparing continuous vs. intermittent terlipressin

– treatment failure in 4.7% vs. 20.7% (p = 0.02, NNT 7)
– mortality 9% vs. 19% (not signi cant)
– rebleeding within 6 weeks in 11.6% vs. 27.9% (p = 0.06)
⚬ Reference - Indian J Gastroenterol 2018 Jul;37(4):313
Somatostatin and somatostatin analogs
● somatostatin and somatostatin analogs (for example, octreotide acetate, vapreotide) 1 , 2
⚬ splanchnic vasoconstrictors inhibit release of vasodilatory peptides

⚬ octreotide may also have local vasoconstrictive e ect
⚬ safe and may be used continuously for ≥ 5 days
⚬ dosing
– octreotide - 50 mcg IV bolus (consider repeat in rst hour if bleeding persists), then continuous
IV infusion 50 mcg/hour for 2-5 days
– vapreotide - 50 mcg IV bolus, then continuous IV infusion 50 mcg/hour
– somatostatin - 250 mcg IV bolus (consider repeat in rst hour if bleeding persists), then
continuous IV infusion 250 mcg/hour for 2-5 days
⚬ only octreotide available in United States
– associated with tachyphylaxis - rapid decrease in response

– more transient e ect than terlipressin
– may be useful adjunct to endoscopic treatment
● e cacy
STUDY
⚬ SUMMARY
somatostatin analogs (somatostatin or octreotide) for acute bleeding from esophageal varices
may reduce initial hemostasis failure and number of transfusions, but may not reduce
mortality or use of balloon tamponade DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2008 Jul 16;(3):CD000193
Details
– based on Cochrane review with wide con dence intervals and heterogeneity
– systematic review of 21 randomized trials comparing somatostatin or octreotide vs. placebo or
no treatment in 2,588 patients suspected of acute bleeding from esophageal varices
– no signi cant di erences in
● mortality in analysis of 16 trials with 2,175 patients (risk ratio [RR] 0.87, 95% CI 0.74-1.04), but
wide con dence intervals cannot exclude clinically relevant di erences
● use of balloon tamponade in analysis of 7 trials with 804 patients
– somatostatin analogs associated with signi cant decrease in
● number of transfusions in analysis of
⚬ 8 higher-quality trials with 1,173 patients (mean di erence [MD] -0.67 transfusions, 95% CI
-1.13 to -0.21 transfusions), but results limited by heterogeneity
⚬ 6 lower-quality trials with 484 patients (MD -1.47 transfusions, 95% CI -1.29 to -0.55
transfusions)
● initial hemostasis failure in analysis of 17 trials with 1,932 patients
⚬ RR 0.68 (95% CI 0.54-0.87)

⚬ NNT 6-21, with 37% failing initial hemostasis in placebo group
⚬ results limited by heterogeneity
● rebleeding in analysis of 7 low-quality trials with 757 patients (RR 0.36, 95% CI 0.19-0.68), but
no signi cant di erence found in analysis of 6 high-quality trials with 606 patients (RR 0.84,
95% CI 0.52-1.37)
– Reference - Cochrane Database Syst Rev 2008 Jul 16;(3):CD000193 (review updated 2012 Feb
15), commentary on earlier version can be found in ACP J Club 2005 Jul-Aug;143(1):16 and
ACP J Club 2002 Nov-Dec;137(3):93
EVIDENCE SYNOPSIS
The addition of vasoactive drug therapy (octreotide, somatostatin, or vapreotide) to endoscopic

therapy may reduce variceal bleeding, in-hospital mortality, and the number and volume of
required transfusions compared to endoscopic therapy alone. There does not appear to be a
signi cant e ect on ≥ 5-day mortality.
STUDY
– SUMMARY
octreotide plus endoscopic therapy may reduce in-hospital mortality, transfusions, and
transfusion volume compared to endoscopic therapy alone in patients with acute variceal
hemorrhage and cirrhosis DynaMed Level 2
COHORT STUDY: Ann Hepatol 2018 Jan;17(1):125
Details
● based on retrospective cohort study
● 316 patients (median age 53 years) with acute variceal hemorrhage and cirrhosis were
treated with endoscopic therapy (endoscopic variceal ligation or cyanoacrylate injection)
plus octreotide or endoscopic therapy alone
⚬ 100 patients had octreotide therapy combined with endoscopic therapy and 216
patients had octreotide therapy alone
⚬ octreotide therapy was 50 mcg IV bolus followed by continuous IV infusion 50 mcg/hour
for 2-5 days
● comparing octreotide plus endoscopic therapy vs. endoscopic therapy alone
⚬ in-hospital mortality 3% vs. 9.7% (p = 0.04)

⚬ transfusion required in 54% vs. 69% ( p = 0.012)
⚬ packed red blood cell units required for transfusion 1 unit vs. 2 units (p = 0.003)
● no signi cant di erence in survival without rebleeding or hospital length of stay

● Reference - Ann Hepatol 2018 Jan;17(1):125
STUDY
– SUMMARY
addition of vasoactive drug therapy (octreotide, somatostatin, or vapreotide) to
endoscopic therapy appears to reduce variceal bleeding, but not mortality
DynaMed Level 2
SYSTEMATIC REVIEW: Hepatology 2002 Mar;35(3):609

Details
● based on systematic review with inadequate trial quality assessment
● systematic review of 8 trials comparing endoscopic therapy plus vasoactive drug therapy
(combination therapy) vs. endoscopic therapy alone in 939 patients with acute variceal
bleeding
⚬ vasoactive drugs included octreotide in 6 trials, somatostatin in 2 trials, and vapreotide
in 1 trial
⚬ duration of infusion was 5 days in 7 trials and 2 days in 1 trial
⚬ endoscopic therapy was injection sclerosis in 6 trials, band ligation in 1 trial, and either
in 1 trial
● no quality assessment for 3 included trials published only as abstracts
● comparing endoscopic plus vasoactive drug therapy vs. endoscopic therapy alone in pooled
analysis
⚬ hemostasis within 48 hours in 88% vs. 76% (relative risk 1.12, 95% CI 1.02-1.23) in
analysis of 4 trials with 559 patients (NNT 8, 95% CI 5-16)
⚬ 5-day hemostasis in 77% vs. 58% (relative risk 1.28, 95% CI 1.18-1.39) in analysis of all
trials (NNT 5, 95% CI 4-8)
⚬ 5-day mortality in 7% vs. 9% in analysis of 6 trials with 759 patients (not signi cant)
● no signi cant di erences in rates of major adverse events in 3 trials

● Reference - Hepatology 2002 Mar;35(3):609 , commentary can be found in Hepatology
2002 Oct;36(4 Pt 1):1023
STUDY
– SUMMARY
addition of vapreotide to endoscopic treatment may help control acute variceal bleeding
DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 2001 Jan 4;344(1):23 | Full Text
Details
● based on randomized trial with baseline di erences
● 227 patients aged 18-75 years with cirrhosis hospitalized for acute upper gastrointestinal
bleeding were randomized to vapreotide (50 mcg bolus then 50 mcg/hour) vs. placebo IV
for 5 days starting mean 2.3 hours after admission
● all patients were randomized within 24 hours of initial bleeding episode and within 6 hours
of hospital admission
● mean time to endoscopy was 2.6 hours after initial randomized drug administration
● 31 patients (13.7%) were excluded because bleeding not related to portal hypertension
● baseline di erences comparing vapreotide vs. placebo
⚬ male sex in 68% vs. 83% (p = 0.02)

⚬ mean serum glucose 166 mg/dL (9.21 mmol/L) vs. 180 mg/dL (9.99 mmol/L) (p = 0.04)
⚬ mean hematocrit 29% vs. 26.5% (p = 0.05)
● comparing vapreotide vs. placebo
⚬ controlled bleeding at time of endoscopy in 69% vs. 54% (p = 0.03, NNT 7)

⚬ survival and control of bleeding at day 5 in 66% vs. 50% (p = 0.02, NNT 7)
⚬ mean units of blood transfused within 5 days 2 vs. 2.8 (p = 0.04)
⚬ 42-day mortality 14% vs. 21% (not signi cant)
● no signi cant di erences in recurrent bleeding, beta-blocker administration after day 5, or
duration of hospitalization
● Reference - N Engl J Med 2001 Jan 4;344(1):23 full-text , commentary can be found in J
Hepatol 2002 Jul;37(1):167
STUDY
● SUMMARY
somatostatin and terlipressin appear to have similar 30-day mortality in patients with cirrhosis
and gastric variceal bleeding DynaMed Level 2
COHORT STUDY: Saudi J Gastroenterol 2016 May;22(3):220 | Full Text
Details
⚬ 311 patients with cirrhosis and gastric variceal bleeding treated with terlipressin or somatostatin
were included
⚬ no signi cant di erence in risk of 30-day mortality comparing terlipressin and somatostatin
⚬ Reference - Saudi J Gastroenterol 2016 May;22(3):220 full-text
Comparative efficacy
EVIDENCE SYNOPSIS
Somatostatin and somatostatin analogs appear similarly e ective for controlling upper
gastrointestinal variceal bleeding in patients with cirrhosis. Short-acting octreotide may have bene t
for reducing the risk of failing initial hemostasis compared to terlipressin and vasopressin.
STUDY
⚬ SUMMARY
somatostatin, octreotide, and terlipressin each initiated prior to endoscopic therapy may
have similar efficacy for control of upper gastrointestinal variceal bleeding in patients with
liver cirrhosis DynaMed Level 2
RANDOMIZED TRIAL: Hepatology 2014 Sep;60(3):954
Details
– based on randomized trial without blinding
– 1,034 patients with liver cirrhosis and signi cant upper gastrointestinal bleeding were
randomized to 1 of 3 vasoactive medications initiated prior to endoscopic therapy
● somatostatin 250 mcg IV bolus then 250 mcg/hour continuous infusion for 5 days
● octreotide 50 mcg IV bolus then 25 mcg/hour continuous infusion for 5 days
● terlipressin 2 mg IV bolus then 1 mg IV every 6 hours for 5 days
– 780 patients (mean age 53 years, 85% male) with variceal bleeding were included in analyses
● 209 patients had no variceal bleeding on endoscopy and discontinued vasoactive

medication
● 45 patients dropped out or were lost to follow-up
– trial designed to test noninferiority of somatostatin, but conventional statistical analyses

performed after noninferiority met
– treatment success de ned as bleeding control without rescue treatment, rebleeding, or death
at end of vasoactive drug treatment
– comparing somatostatin vs. octreotide vs. terlipressin
● treatment success in 83.4% vs. 83.8% vs. 86.2% (not signi cant among groups)
● recurrent bleeding in 4.8% vs. 4.4% vs. 3.4% (not signi cant among groups)
● mean time to bleeding control 8.2 hours vs. 8.1 hours vs. 7.8 hours (not signi cant among
groups)
● mortality 8.9% vs. 8.8% vs. 8% (not signi cant among groups)
● hyponatremia in 1.5% vs. 1.2% vs. 11.5% (p < 0.001 among groups)
– no signi cant di erences in other adverse events

– Reference - Hepatology 2014 Sep;60(3):954 , editorial can be found in Hepatology 2014
Sep;60(3):789
STUDY
⚬ SUMMARY
terlipressin and octreotide may have similar efficacy for control of esophageal variceal
bleeding in patients with cirrhosis DynaMed Level 2
RANDOMIZED TRIAL: Am J Gastroenterol 2009 Mar;104(3):617
Details
– based on randomized trial with baseline di erences
– 513 patients with cirrhosis presenting to emergency room with upper gastrointestinal bleed
were randomized to terlipressin vs. octreotide for 72 hours
● terlipressin given as 2 mg IV bolus, then 1 mg every 6 hours
● octreotide given as 100 mcg IV bolus, then 50 mcg/hour continuous infusion
● placebo IV infusions used to maintain blinding
– 324 patients (mean age 53 years, 71% male) had esophagogastroduodenoscopy-con rmed
esophageal variceal bleeding and were included in analysis
– all patients received endoscopic band ligation ≤ 24 hours after admission
– at enrollment, active bleeding during endoscopy in 16% terlipressin vs. 25.5% octreotide
patients (p = 0.034)
– comparing terlipressin vs. octreotide
● control of variceal bleeding in 92.3% vs. 95.6% (not signi cant)

● mortality 5.5% vs. 4.3% (not signi cant)
– no signi cant di erences in mean units of packed red blood cell transfused and mean
duration of hospitalization
– Reference - Am J Gastroenterol 2009 Mar;104(3):617 , commentary can be found in Am J
Gastroenterol 2009 Sep;104(9):2351
STUDY
⚬ SUMMARY
octreotide may reduce risk of failing initial hemostasis compared to terlipressin,
vasopressin, or no treatment for acute esophageal variceal bleeding DynaMed Level 2
SYSTEMATIC REVIEW: Canadian Agency for Drugs and Technologies in Health (CADTH) Health
Technology Assessment 2008 Jul PDF
Details
– based on systematic review with heterogeneity
– systematic review of 82 randomized trials of octreotide for various conditions
– 36 trials evaluated short-acting octreotide for emergency management of variceal bleeding
compared to
● placebo or no treatment in 21 trials with 2,953 patients
● sclerotherapy in 7 trials with 1,043 patients
● balloon tamponade in 2 trials with 92 patients
● somatostatin, terlipressin, or vasopressin in 11 trials with 909 patients
– ndings for esophageal variceal bleeding with short-acting octreotide

● reduced risk of failing initial hemostasis compared to placebo or no treatment, terlipressin,
and vasopressin
● reduced risk of rebleeding compared to placebo or no treatment
● reduced in-hospital mortality compared to placebo or no treatment, but increased in-
hospital mortality in 1 trial excluded from meta-analysis
● no signi cant di erences in mortality using longest follow-up time
– Reference - Canadian Agency for Drugs and Technologies in Health (CADTH) Health Technology
Assessment 2008 Jul PDF
STUDY
⚬ SUMMARY
terlipressin may have more sustained effect on portal venous flow and hepatic venous
pressure gradient than octreotide DynaMed Level 3
RANDOMIZED TRIAL: Am J Gastroenterol 2005 Mar;100(3):631
Details
– based on small randomized trial without clinical outcomes
– 42 patients (mean age 48 years, 93% male) with cirrhosis and history of variceal bleeding were
randomized to octreotide (100 mcg IV bolus, then 250 mcg/hour continuous infusion) vs.
terlipressin 2 mg IV bolus
– portal venous ow (PVF) and hepatic venous pressure gradient (HVPG) were assessed by
Doppler ultrasound at 1, 5, 10, 15, 20, and 25 minutes after start of medication
– octreotide associated with
● signi cantly decreased HVPG (-44.5%) and PVF (-30.6%) at 1 minute compared to baseline (p
< 0.05)
● HVPG and PVF rapidly returned to baseline after 1 minute and no signi cant di erences by
5 minutes
– terlipressin associated with
● signi cantly decreased HVPG (-18.3%) and PVF (-32.6%) at 1 minute compared to baseline (p
< 0.05)
● e ect sustained at all time points
– Reference - Am J Gastroenterol 2005 Mar;100(3):631
Antibiotic prophylaxis
● patients with cirrhosis and variceal hemorrhage have high risk of bacterial infections 1 , 2
⚬ bacterial infections associated with recurrent bleeding and increased mortality

⚬ patients with more severe liver disease (Child-Pugh class B and C) are at greatest risk
● short-term use of prophylactic antibiotics associated with reduced bacterial infections and increases
survival in patients with or without ascites 1 , 2
● recommendations for antibiotic prophylaxis
⚬ American Association for the Study of Liver Diseases recommends starting short-term antibiotic
prophylaxis (maximum 7 days) concurrent with vasoactive therapy in any patient with cirrhosis and
gastrointestinal hemorrhage 1
– ceftriaxone 1 g IV once daily is preferred, especially for patients with advanced cirrhosis,
patients on quinolone prophylaxis, and in hospitals with high prevalence of quinolone-resistant
organisms
– consider discontinuing antibiotics if bleeding resolves and vasoactive therapy has ceased
⚬ Baveno VI 2015 international workshop consensus recommends starting prophylactic antibiotics at
time of admission (Baveno Level 1a, Grade A) 3

– consider individual patient risks and local antimicrobial susceptibility patterns to determine
appropriate rst line antibiotic for prophylaxis at each treatment center (Baveno Level 5, Grade
D)
– consider ceftriaxone 1g once daily in
● patients with advanced cirrhosis (Baveno Level 1b, Grade A)

● hospitals with high prevalence of quinolone-resistant bacterial infections (Baveno Level 5,
Grade D)
● patients on previous quinolone prophylaxis (Baveno Level 5, Grade D)
– patients with Child-Pugh class A cirrhosis have very low risk of bacterial infection and mortality
(Baveno Level 2b, Grade B), but insu cient evidence to determine if antibiotic prophylaxis can
be avoided in this group
EVIDENCE SYNOPSIS
Antibiotic prophylaxis for patients with cirrhosis and acute gastrointestinal hemorrhage may reduce
bacterial infection but insu cient evidence exists to assess for di erence in mortality. E ects may
be less in Child-Pugh class A patients than for class B and C.
STUDY
⚬ SUMMARY
antibiotic prophylaxis may reduce mortality and bacterial infection in inpatients with
cirrhosis and gastrointestinal bleeding, but evidence does not suggest preferred regimen
DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2010 Sep 8;(9):CD002907
Details
– based on Cochrane review of trials with methodologic limitations
– systematic review of 17 randomized trials evaluating antibiotic prophylaxis in 1,891
hospitalized patients with cirrhosis and gastrointestinal bleeding
– all trials had ≥ 1 methodologic limitation including inadequate blinding, no intention-to-treat
analysis, and inadequate allocation concealment
– antibiotic prophylaxis was compared to placebo or no treatment in 12 trials with 1,241 patients
● antibiotic regimens included
⚬ quinolones orally for 3-7 days (cipro oxacin, nor oxacin, o oxacin)
⚬ cephalosporins
⚬ imipenem-cilastatin 500 mg IV over 20 minutes before and after sclerotherapy
⚬ combination therapy
● antibiotics associated with reduced
⚬ all-cause mortality in analysis of all trials
– risk ratio (RR) 0.79 (95% CI 0.63-0.98)

– NNT 12-228 with mortality in 22% of control group
⚬ proven bacterial infection in analysis of all trials
– RR 0.36 (95% CI 0.27-0.49)

– NNT 4-6 with bacterial infection in 36% of control group
⚬ mortality from bacterial infection (RR 0.43, 95% CI 0.19-0.97) in analysis of 6 trials with
761 patients
⚬ bacteremia (RR 0.25, 95% CI 0.15-0.4) in analysis of 9 trials with 987 patients
⚬ rebleeding (RR 0.53, 95% CI 0.38-0.74) in analysis of 3 trials with 280 patients
⚬ days of hospitalization (weighted mean di erence -1.91 days, 95% CI -3.8 to -0.02 days)
in analysis of 5 trials with 505 patients
– no signi cant di erences in mortality or proven bacterial infection in 5 trials comparing
di erent antibiotic regimens including
● nor oxacin 800 mg/day orally for 7 days plus ceftriaxone 2 g/day IV for rst 3 days vs.
nor oxacin 800 mg/day orally for 7 days
● nor oxacin 800 mg/day vs. o oxacin 400 mg/day orally for 5 days
● nor oxacin 800 mg/day orally vs. ceftriaxone 1 g/day IV for 7 days
● single-dose ceftriaxone 1 g IV vs. 2 g IV before transjugular intrahepatic portosystemic
shunt
● nor oxacin 800 mg/day vs. ampicillin and sulbactam 3 g/day for 7 days
– Reference - Cochrane Database Syst Rev 2010 Sep 8;(9):CD002907 , commentary on earlier
version can be found in ACP J Club 2002 Nov-Dec;137(3):94
– systematic review of 12 placebo-controlled trials (included in Cochrane review, same authors
as Cochrane review) can be found in Aliment Pharmacol Ther 2011 Sep;34(5):509
STUDY
⚬ SUMMARY
ceftriaxone prophylaxis may reduce bacterial infections compared to norfloxacin
prophylaxis, but insufficient evidence for difference in mortality in patients with advanced
cirrhosis and gastrointestinal hemorrhage DynaMed Level 2
RANDOMIZED TRIAL: Gastroenterology 2006 Oct;131(4):1049
Details
– based on randomized trial without intention-to-treat analysis
– 124 patients with advanced cirrhosis and gastrointestinal hemorrhage were randomized to
ceftriaxone 1 g/day IV vs. nor oxacin 400 mg orally twice daily for 7 days
– 111 patients (90%) were included in analysis
– proven infection de ned as positive blood culture, ascitic uid polymorphonuclear count ≥
250/mm3, positive urine culture plus urinary leukocytosis, or other infections
– possible infection de ned as fever > 6 hours, leukocytosis > 15,000/mm3, or immature
neutrophil count > 500/mm3 with negative cultures

– comparing ceftriaxone vs. nor oxacin
● proven or possible infection in 11% vs. 33% (p = 0.01, NNT 5)

● proven infection in 11% vs. 26% (p = 0.07)
● spontaneous bacteremia or bacterial peritonitis in 2% vs. 12% (p = 0.06)
● 10-day mortality 9% vs. 11% (not signi cant)
– 6 of 7 gram-negative bacilli isolated in nor oxacin group were resistant to quinolones

– no adverse events related to either medication observed
– Reference - Gastroenterology 2006 Oct;131(4):1049
–
DynaMed Commentary
Statistics (p values) in full-text are di erent from abstract.
– see Nor oxacin for FDA BOXED WARNING regarding risk of tendonitis with systemic
uoroquinolones
STUDY
⚬ SUMMARY
DynaMed Level 2
COHORT STUDY: PLoS One 2013;8(4):e61666
Details
cefazolin as prophylactic antibiotic may result in rebleeding and may not aid in infection
prevention compared in ceftriaxone in patients with cirrhosis and gastrointestinal bleeding
– based on retrospective cohort study
– 102 patients aged mean 50 years old with cirrhosis and gastrointestinal bleeding treated with
IV cefazolin were age-matched to patients treated with IV ceftriaxone as prophylactic
antibiotics
– comparing cefazolin vs. ceftriaxone
● among 51 patients with Child-Pugh Class B and C
⚬ rebleeding in 66.7% vs. 25% (p = 0.011, NNH 2)

⚬ infection prevention in 77.8% vs. 87.5% (0.072)
● among 51 patients with Child-Pugh Class A
⚬ infection prevention in 93.1% vs. 90.9% (not signi cant)

⚬ rebleeding in 32% vs. 40.9% (not signi cant)
– Reference - PLoS One 2013;8(4):e61666

Coagulation modulators
EVIDENCE SYNOPSIS
Recombinant activated factor VII (rFVIIa) does not appear to reduce mortality or improve initial
bleeding in patients with cirrhosis and upper gastrointestinal bleeding. It may reduce the rate of
early rebleeding.
STUDY
⚬ SUMMARY
rFVIIa may reduce early rebleeding, but may not improve initial bleeding control or 5-day
survival, in patients with cirrhosis and upper gastrointestinal bleeding DynaMed Level 2
RANDOMIZED TRIAL: J Hepatol 2014 Aug;61(2):252
Details
– based on meta-analysis of individual patient data from 2 randomized trials with methodologic
limitations
– meta-analysis of individual patient data from 2 randomized trials including 497 patients (mean
age 54 years, 74% male) with cirrhosis and upper gastrointestinal bleeding randomized to
rFVIIa vs. placebo
– both trials had methodologic limitations including clinical heterogeneity across participating
sites and subgroup analysis
– 84% had variceal origin bleeding and 62% had active variceal bleeding at endoscopy
– 57% (283 patients) had both active variceal bleeding at endoscopy and Child-Pugh scores > 8
(high risk)
– comparing rFVIIa vs. placebo in analysis of all patients
● failure to control bleeding within 24 hours in 8% vs. 9% (not signi cant)

● rebleeding within 5 days in 4% vs. 7% (p = 0.004)
● 5-day survival 7% vs. 7% (not signi cant)
– comparing rFVIIa vs. placebo in subgroup analysis of high-risk patients
● failure to control bleeding within 24 hours in 9% vs. 13% (not signi cant)
● rebleeding within 5 days in 3% vs. 10% (p = 0.006)
● 5-day survival 8% vs. 13% (not signi cant)
– Reference - J Hepatol 2014 Aug;61(2):252
STUDY
⚬ SUMMARY
rFVIIa does not appear to reduce mortality in patients with liver disease and upper
gastrointestinal bleeding DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2012 Mar 14;(3):CD004887
Details
– based on Cochrane review limited by clinical heterogeneity and wide con dence intervals
– systematic review of 2 randomized trials comparing rFVIIa vs. placebo in 510 patients with liver
disease and upper gastrointestinal bleeding
● 1 trial included patients with all Child-Pugh scores and evaluated rFVIIa 100 mcg/kg
● 1 trial included only patients with Child-Pugh scores > 8 (advanced cirrhosis) and evaluated
2 doses of rFVIIa (300 mcg/kg and 600 mcg/kg)
● 5-day mortality in analysis of 2 trials with 493 patients, but wide con dence intervals cannot
exclude clinically relevant di erences
● 42-day mortality in analysis of 2 trials with 491 patients, but wide con dence intervals
cannot exclude clinically relevant di erences
● thromboembolic adverse events in analysis of 2 trials with 507 patients, but results may be
limited by di erences in rFVIIa dosage and timing of administration
● number of packed red blood cell transfusions within 24 hours or within 5 days
– Reference - Cochrane Database Syst Rev 2012 Mar 14;(3):CD004887
STUDY
● SUMMARY
tranexamic acid does not reduce death due to bleeding or 28-day all-cause mortality in adults
with acute gastrointestinal bleeding DynaMed Level 1
RANDOMIZED TRIAL: Lancet 2020 Jun 20;395(10241):1927 | Full Text
Details
⚬ 12,009 adults (mean age 58 years) with acute upper or lower gastrointestinal bleeding were
randomized to tranexamic acid vs. normal saline placebo and were followed for up to 28 days
– all patients were considered at risk of bleeding to death due to hypotension, tachycardia, or
signs of shock, or were likely to need transfusion, urgent endoscopy, or surgery
– variceal bleeding suspected in 45%
⚬ tranexamic acid dosing: 1 g in 100 mL 0.9% sodium chloride (normal saline) IV over 10 minutes
(loading dose) followed by 3 g in 1 L normal saline at 125 mg/hour for 24 hours (maintenance dose)
⚬ primary outcome was changed from 28-day all-cause mortality due to death from bleeding within 5
days (relative risk reduction of 25% was considered clinically important)
⚬ 99.4% included in analysis
⚬ comparing tranexamic acid vs. placebo
– death due to bleeding ≤ 5 days in 3.7% vs. 3.8% (risk ratio 0.99, 95% CI 0.82-1.18)
– 28-day all-cause mortality 9.5 vs. 9.2% (not signi cant)
– venous thromboembolic events in 0.8% vs. 0.4% (p < 0.05, NNH 250), signi cant, but may not be
clinically important
– seizure in 0.6% vs. 0.4% (p < 0.5, NNH 500), signi cant, but may not be clinically important
– myocardial infarction or stroke in 0.7% vs. 0.8% (not signi cant)
⚬ no signi cant di erence in death due to bleeding at 24 hours or 28 days or in rebleeding at 24

hours, 5 days, or 28 days
⚬ Reference - HALT-IT trial (Lancet 2020 Jun 20;395(10241):1927 full-text )
STUDY
● SUMMARY
no randomized trials found evaluating vitamin K for upper gastrointestinal bleeding in patients
with liver disease
COCHRANE REVIEW: Cochrane Database Syst Rev 2015 Jun 9;(6):CD004792
Details
⚬ based on Cochrane review
⚬ Reference - Cochrane Database Syst Rev 2015 Jun 9;(6):CD004792
STUDY
● SUMMARY
no randomized trials found evaluating antifibrinolytic amino acids for treatment of upper
gastrointestinal bleeding in patients with liver disease and acquired coagulation disorder
COCHRANE REVIEW: Cochrane Database Syst Rev 2015 Jun 9;(6):CD006007
Details
⚬ Reference - Cochrane Database Syst Rev 2015 Jun 9;(6):CD006007
Beta blockers
● beta blockers should not be used during acute variceal bleeding episodes 1
● after acute variceal hemorrhage, combination of nonselective beta blockers (NSBBs) plus endoscopic
variceal ligation (EVL) considered best option for secondary prophylaxis of variceal hemorrhage
Baveno Grade A, Level 1a 3
⚬ repeat EVL every 1-4 weeks until obliteration
⚬ dosing recommendations from AASLD include 1
– propranolol
● initial dose 20 mg - 40 mg orally twice daily

● maximum dose 320 mg/day in patients without ascites, 160 mg/day in patients with ascites
● adjust every 2-3 days to maintain resting heart rate 55 - 60 bpm and systolic blood pressure
> 90 mm Hg
– nadolol
● initial dose 20 mg - 40 mg orally once daily

● maximum dose 160 mg/day in patients without ascites, 80 mg/day in patients with ascites
● adjust every 2-3 days to maintain resting heart rate 55 - 60 bpm and systolic blood pressure
> 90 mm Hg
⚬ contraindications for NSBB usage may be absent at therapy initiation but should be monitored
during disease evolution (Baveno Grade D, Level 5) 3

⚬ in patients with refractory ascites, close monitoring indicated and consideration of discontinuation
or reduction of dose in patients that develop (Baveno Grade C, Level 4) 3

– low blood pressure
– impairment of renal function
⚬ addition of isosorbide-5-mononitrate to beta blockers has been suggested to improve e ciency of

treatment in hemodynamic nonresponders (Baveno Grade D, Level 5) but isosorbide mononitrate
in addition to beta blockers does not appear to reduce rebleeding or mortality compared to beta
blockers alone in patients with esophageal varices 1 , 3
⚬ see Esophageal Variceal Hemorrhage - Prevention of Rebleeding for details
● see Esophageal Variceal Hemorrhage - Prevention of Rebleeding for role of beta blockers for primary
prophylaxis of variceal bleeding
Other medications
STUDY
● SUMMARY
addition of simvastatin to endoscopic variceal ligation and nonselective beta blockers for
variceal bleeding may increase short-term survival, but may not reduce rebleeding risk in
patients with cirrhosis DynaMed Level 2
RANDOMIZED TRIAL: Gastroenterology 2016 May;150(5):1160
Details
⚬ based on randomized trial with con dence interval that includes di erences that may not be
clinically important
⚬ 158 patients with cirrhosis (Child-Pugh class B in 65%) and variceal bleeding in previous 5-10 days
were randomized to simvastatin (titrated to target dose 40 mg/day) vs. placebo for up to 2 years
⚬ all patients had secondary prophylaxis with endoscopic variceal ligation and nonselective beta
blockers for variceal bleeding
⚬ median treatment duration 337 days with simvastatin and 329 days with placebo
⚬ median follow-up 371 days with simvastatin and 382 days with placebo
⚬ 93% included in analysis
⚬ comparing simvastatin vs. placebo
– all-cause mortality 9% vs. 22% (hazard ratio 0.39, 95% CI 0.15-0.99, NNT 8), signi cant but
con dence interval includes di erences that may not be clinically important
– rebleeding in 25% vs. 28% (not signi cant)
– adverse events in 81.4% vs. 75.9% (not signi cant)
– discontinuation of nonselective beta blockers in 17% vs. 23% (no p value reported)
⚬ no signi cant di erences in risk of portal hypertension, ascites, spontaneous bacterial peritonitis,
or need for transfusion
⚬ most common adverse events associated with simvastatin were hepatic encephalopathy (3
patients), gynecomastia (2 patients), iron de ciency anemia (2 patients), and rhabdomyolysis (2
patients)
⚬ Reference - BLEPS trial (Gastroenterology 2016 May;150(5):1160 ), editorial can be found in
Gastroenterology 2016 May;150(5):1077
Endoscopic Therapy
Types and clinical role
● esophagogastroduodenoscopy (EGD) should be performed within 12 hours of admission (in

hemodynamically stable patients) to diagnose and treat variceal hemorrhages with endoscopic
variceal ligation or sclerotherapy 1
● ideally, endoscopy should be performed on empty stomach 2
⚬ nasogastric lavage often not e cient and is associated with complications

⚬ erythromycin 250 mcg IV over 5 minutes may be administered 20 minutes before endoscopy to act
as motility agonist, empty stomach, and reduce endoscopy time
● endoscopic therapy should be performed once variceal bleeding is diagnosed 2
● endoscopic variceal ligation (EVL), also called endoscopic band ligation (EBL) 1 , 2
⚬ preferred method of endoscopic therapy

⚬ most frequent complications include super cial ulcerations, esophageal strictures, and delayed
bleeding after rubber rings fall
● endoscopic sclerotherapy (EST), also called endoscopic injection sclerotherapy (EIS) 1 , 2
⚬ recommended when ligation is technically di cult (poor visualization) or unavailable

⚬ injection of sclerosant into or adjacent to varix
⚬ increased complications compared to EVL
● injection of tissue adhesive (such as cyanoacrylate) may be used for gastric varices, but cyanoacrylate
glue injection not approved for treatment of gastric varices in United States 1
● endoscopic variceal ligation should only be used on small gastric varices when both the mucosal and
contralateral wall of the vessel can be suctioned into the ligator to avoid band displacement several
days later that can leave exposed ulcer over the vessel and catastrophic bleeding 1
● Baveno VI 2015 international workshop consensus recommendations on endoscopic therapy 3
⚬ for patients with acute esophageal variceal bleeding, ligation is recommended (Baveno Level 1b,
Grade A)
⚬ endoscopic therapy with tissue adhesive (such as N-butyl-cyanoacrylate) is recommended for
– acute bleeding from isolated gastric varices (Baveno Level 1b, Grade A)
– gastroesophageal varices type 2 that extend beyond the cardia (Baveno Level 5, Grade D)
⚬ in bleeding from gastroesophageal varices type 1, EVL or tissue adhesive can be used (Baveno
Level 5, Grade D)
⚬ consider additional glue injection (2-4 weeks after initial treatment), beta-blocker therapy, both
glue injection and beta-blocker therapy, or transjugular intrahepatic portosystemic shunt (TIPS) for
prevention of rebleeding (Baveno Level 5, Grade D)
Efficacy
Endoscopic variceal ligation
STUDY
● SUMMARY
endoscopic variceal ligation reduces rebleeding within 5 days in patients with acute esophageal
variceal hemorrhage but no active bleeding at endoscopy DynaMed Level 1
RANDOMIZED TRIAL: Gut 2009 Sep;58(9):1275
Details
⚬ 93 patients aged 17-75 years with cirrhosis and acute esophageal variceal bleeding, but no active
variceal bleeding at endoscopy, were randomized to endoscopic variceal ligation banding plus
terlipressin 1 mg every 6 hours IV for 2 days (combination therapy) vs. terlipressin 1 mg every 6
hours IV for 5 days
⚬ 96.7% completed trial, but all patients were included in analysis
⚬ treatment failure de ned as failure to control acute bleeding, very early rebleeding, or death within
5 days
⚬ comparing combination therapy vs. terlipressin alone
– bleeding at 48-120 hours in 0% vs. 15% (p = 0.006, NNT 7)

– treatment failure in 2% vs. 24% (p = 0.002, NNT 5)
– mean transfusion within 48 hours of endoscopy 1.3 units vs. 1.9 units (p = 0.036)
– mean transfusion within 49-120 hours of endoscopy 0.2 units vs. 1.4 units (p = 0.002)
⚬ no signi cant di erences in length of hospital stay or 42-day mortality

⚬ Reference - Gut 2009 Sep;58(9):1275 , editorial can be found in Gut 2009 Sep;58(9):1182 ,
commentary can be found in Gut 2010 Mar;59(3):417
STUDY
● SUMMARY
endoscopic variceal ligation reduces acute bleeding compared to sclerotherapy in patients with
acute variceal bleeding receiving somatostatin DynaMed Level 1
RANDOMIZED TRIAL: J Hepatol 2006 Oct;45(4):560
Details
⚬ 182 adults with endoscopy-con rmed acute esophageal variceal bleeding and suspected cirrhosis
were randomized to emergency endoscopic therapy with endoscopic variceal ligation vs.
sclerotherapy
– all patients received somatostatin 250 mcg/hour IV continuously for rst 5 days beginning
immediately after admission with additional bolus of 250 mcg every 6 hours throughout 5-day
infusion period
– emergency endoscopic therapy was performed during diagnostic endoscopy within 6 hours of
admission
⚬ 3 patients were not included in analysis after withdrawal from trial
⚬ treatment failure de ned as failure to control acute bleeding, early rebleeding, or death within 5
days
⚬ comparing endoscopic variceal ligation vs. sclerotherapy
– treatment failure in 10% vs. 24% (p = 0.02, NNT 8)

– failure to control acute bleeding episode in 4% vs. 15% (p = 0.02, NNT 9)
– mean time from hospital admission to cessation of bleeding 6.5 hours vs. 8.4 hours (p = 0.05)
– major adverse events (primarily aspiration pneumonia, sepsis, or esophageal bleeding ulcer) in
4% vs. 13% (p = 0.04, NNT 12)
– mortality within 42 days 13% vs. 21% (not signi cant)
⚬ no signi cant di erences in rebleeding at 5 days, rebleeding at 5-42 days, or in length of hospital
stay
⚬ Reference - J Hepatol 2006 Oct;45(4):560
STUDY
● SUMMARY
endoscopic band ligation associated with increased rebleeding and mortality compared with
endoscopic cyanoacrylate variceal obliteration in patients with GOV1 gastric varices
DynaMed Level 2
COHORT STUDY: Clin Mol Hepatol 2016 Dec;22(4):487 | Full Text

Details
⚬ 91 patients (mean age 56.3 years, 85.7% male) with GOV1 gastric variceal hemorrhage (39 patients),
bleeding stigmata (42 patients), or bleeding history (10 patients) treated with endoscopic band
ligation (EBL, 51 patients) or endoscopic cyanoacrylate obliteration (ECO) (40 patients) were
evaluated for bleeding and mortality outcomes
⚬ patients with fundal gastric varices (GOV2, IGV1, isolated gastric varices type 2 [IGV2]) or
hepatocellular carcinoma were excluded
⚬ comparing EBL vs. ECO
– mortality in 21.6% vs. 5% (p = 0.05)

– rebleeding in 27.5% vs. 2.5% (p < 0.005)
– hemostasis rate in subset of 39 patients with active bleeding 82.6% vs. 100% (p < 0.078)
⚬ Reference - Clin Mol Hepatol 2016 Dec;22(4):487 full-text
STUDY
● SUMMARY
endoscopic ligation appears to have lower mortality and complication rates than sclerotherapy
for actively or recently bleeding esophageal varices in patients with cirrhosis DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 1992 Jun 4;326(23):1527 | Full Text
Details
⚬ based on randomized trial with early termination
⚬ 130 adults (mean age 52 years, 80% male) with cirrhosis and actively or recently bleeding
esophageal varices were randomized to ligation vs. sclerotherapy
⚬ repeated treatment was provided as needed for recurrent bleeding until all varices eradicated,
then endoscopy performed every 3 months
⚬ physicians providing follow-up care were not blinded
⚬ mean follow-up for 68% patients who survived or were followed > 30 days was 320 days
⚬ trial terminated early without prede ned stopping rule after signi cant di erences in complications
and mortality were found at 24-month interim analysis
⚬ comparing ligation vs. sclerotherapy
– mortality 28% vs. 45% (p = 0.04, NNT 6)

– complication rate 2% vs. 22% (p < 0.001, NNT 5)
– number of treatments needed 4 vs. 5 (p = 0.056)
– rebleeding in 36% vs. 48% (p = 0.07)
⚬ most common complications were esophageal stricture or perforation, pneumonia, pleural

e usions, bacterial peritonitis
⚬ Reference - N Engl J Med 1992 Jun 4;326(23):1527 full-text
STUDY
● SUMMARY
ligation may be more effective than pharmacologic therapy for patients with ongoing cirrhosis
and ongoing esophageal variceal bleeding DynaMed Level 2
META-ANALYSIS: Endoscopy 2001 Sep;33(9):737
Details
⚬ based on meta-analysis with indirect comparisons
⚬ meta-analysis of 13 randomized trials with 1,269 patients with cirrhosis and ongoing esophageal
variceal bleeding
– 4 trials with 335 patients comparing pharmacologic regimens (vasopressin plus nitroglycerin,
octreotide acetate, somatostatin, terlipressin)
– 6 trials with 658 patients comparing sclerotherapy vs. ligation
– 2 trials with 168 patients comparing pharmacologic treatment vs. endoscopic treatments
– 1 trial with 108 patients comparing vasopressin vs. esophageal tamponade
⚬ cumulative success rate (percentage of patients with bleeding controlled)
– 91% (95% CI 82.4%-96.3%) with ligation

– 68.7% (95% CI 61.7%-75.2%) with vasopressive therapy (p < 0.002 vs. ligation)
– 75.97% (95% CI 68.1%-82.6%) with vasoactive therapy (p < 0.01 vs. ligation)
– 81.1% (95% CI 71.7%-88.4%) with sclerotherapy (not signi cant compared to ligation)
⚬ no signi cant di erences comparing sclerotherapy to pharmacologic therapy

⚬ Reference - Endoscopy 2001 Sep;33(9):737
STUDY
● SUMMARY
compared to placing maximum of 6 rubber bands per endoscopic treatment session for
esophageal varices, placement of unlimited number of rubber bands per session may not reduce
overall number of sessions or improve patient outcomes DynaMed Level 2
RANDOMIZED TRIAL: Am J Gastroenterol 2007 Jul;102(7):1372
Details
⚬ based on quasi-randomized trial with wide con dence intervals
⚬ 86 patients (mean age 55 years, 98% male) having endoscopic variceal ligation (EVL) were assigned
to a series of EVL treatments with as many rubber bands as could be possibly placed vs. up to
maximum of 6 bands
– 62 patients had initial EVL for acute upper gastrointestinal bleed, 10 actively bleeding
– 24 patients had initial EVL as primary prophylaxis due to intolerance of beta-blocker therapy
⚬ mean number of bands placed in rst session was 8 with unlimited bangs vs. 5.4 with ≤ 6 bands (p
< 0.05)
⚬ no signi cant di erences in number of bands placed in subsequent sessions
⚬ obliteration was achieved by 53% in unlimited-band group vs. 59% in ≤ 6-band group
⚬ number of sessions to obliteration and mortality were similar in both groups
⚬ placement of > 6 bands was associated with greater procedure times and more mis red bands
⚬ Reference - Am J Gastroenterol 2007 Jul;102(7):1372
● 1-week interval between endoscopic ligation may reduce time to variceal eradication without
increasing adverse events compared to 2-week interval in randomized trial of 90 patients with acute
esophageal bleeding and successful ligation at presentation (Hepatology 2016 Aug;64(2):549 )
STUDY
● SUMMARY
addition of sclerotherapy to endoscopic variceal ligation may reduce time to variceal obliteration
with fewer sessions compared to endoscopic variceal ligation alone in patients with cirrhosis
and bleeding gastric varices DynaMed Level 2
RANDOMIZED TRIAL: Gastrointest Endosc 2017 Aug;86(2):307

Details
⚬ 120 patients with cirrhosis and bleeding gastroesophageal varices were randomized to endoscopic
variceal ligation plus sclerotherapy vs. endoscopic variceal ligation alone
⚬ sclerotherapy was injection of 2 mL ethanolamine oleate 5% into the varix below deployed band(s)
during endoscopic variceal ligation
⚬ follow-up was 6 months post-obliteration of varices
⚬ comparing endoscopic variceal ligation plus sclerotherapy vs. endoscopic variceal ligation alone
– mean weeks until variceal obliteration 8.6 vs. 15.6 (p < 0.001)
– mean endoscopy sessions until variceal obliteration 2.22 vs. 3.43 (p < 0.001)
– mean blood transfusion units per patient 1.5 vs. 2.3 (p < 0.001)
⚬ no signi cant di erences in adverse events, recurrence rates, 12-month survival, or rebleeding
rates after obliteration
⚬ Reference - Gastrointest Endosc 2017 Aug;86(2):307
STUDY
● SUMMARY
endoscopic variceal ligation and endoscopic sclerotherapy may each be effective for eradicating
esophageal varices, but endoscopic variceal ligation may hasten time to eradication and reduce
number of eradication sessions needed DynaMed Level 2
RANDOMIZED TRIAL: Cureus 2018 Jul 13;10(7):e2977 | Full Text
Details
⚬ 60 patients with portal hypertension and grade 3 or 5 bleeding esophageal varices were
randomized to endoscopic variceal ligation, with repeat banding after 2 weeks if needed vs.
endoscopic sclerotherapy using intravariceal or paravariceal injection of 2 mL of 5% ethanolamine
oleate, with repeat injections every 2 weeks if needed
⚬ follow-up was 2 years
⚬ no signi cant di erence in recurrent bleeding (1 patient in endoscopic variceal ligation group)
⚬ comparing endoscopic variceal ligation vs. endoscopic sclerotherapy
– number of endoscopic sessions for eradication of varices 3.73 vs. 5.36 (p < 0.05)
– mean number of days taken for eradication of varices 78.6 days vs. 134.6 days (p < 0.05)
⚬ Reference - Cureus 2018 Jul 13;10(7):e2977 full-text
STUDY
● SUMMARY
aggressive endoscopic band ligation reported to have 4.6% incidence of rebleeding at 2 years in
patients with esophageal variceal bleeding DynaMed Level 3
CASE SERIES: Scand J Gastroenterol 2015;50(9):1059
Details
⚬ based on case series
⚬ 176 patients with esophageal variceal bleeding were treated with aggressive endoscopic band
ligation (initial banding followed by repeat endoscopy and banding every 1-3 weeks until varices
were stabilized or obliterated) and were followed for 1 year, with periodic endoscopy sessions
throughout
⚬ incidence of rebleeding
– 2.3% at 6 months
– 3.4% at 1 year
– 4.6% at 2 years
⚬ 1 patient died secondary to a gastric variceal bleed

⚬ Reference - Scand J Gastroenterol 2015;50(9):1059
Sclerotherapy
STUDY
● SUMMARY
sclerotherapy does not appear to improve bleeding control or reduce mortality compared to
vasoactive drugs and may increase adverse events in patients with cirrhosis and acute variceal
bleeding DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2010 Mar 17;(3):CD002233
Details
⚬ based on Cochrane review limited by clinical heterogeneity
⚬ systematic review of 17 randomized trials comparing sclerotherapy vs. vasoactive drugs in 1,817
patients with cirrhosis and acute variceal bleeding
⚬ vasoactive drugs included octreotide in 10 trials, somatostatin in 5 trials, terlipressin in 1 trial, and
vasopressin in 1 trial
⚬ de nitions of major outcomes (control of bleeding, failure to control bleeding) unclear and varied
across trials
⚬ no signi cant di erences comparing sclerotherapy with each vasoactive drug for any outcomes
(failure to control bleeding, 5-day failure rate, rebleeding, mortality, transfused blood units), but
trends toward slight advantage with sclerotherapy
⚬ sclerotherapy associated with increased risk of
– adverse events (risk di erence 8%, 95% CI 3%-14%) in analysis of 12 trials with 1,178 patients,
results limited by heterogeneity (p = 0.02)
– serious adverse events (risk di erence 5%, 95% CI 2%-8%) in analysis of 5 trials with 602 patients
⚬ Reference - Cochrane Database Syst Rev 2010 Mar 17;(3):CD002233
Injection of tissue adhesive
STUDY
● SUMMARY
endoscopic N-butyl-2-cyanoacrylate glue injection reduces rebleeding compared to band
ligation in patients with acute bleeding gastric varices and portal hypertension
DynaMed Level 1
COCHRANE REVIEW: Cochrane Database Syst Rev 2015 May 12;(5):CD010180
Details
⚬ systematic review of 6 randomized trials comparing endoscopic N-butyl-2-cyanoacrylate glue
injection vs. other endoscopic procedures in patients with portal hypertension and acute bleeding
gastric varices
– all trials administered cyanoacrylate by intravariceal injection (range 1-6 injections) with sessions
repeated at 1-4 weeks until varices eradicated
– 1 trial compared di erent cyanoacrylate dosages, 1 trial compared alcohol-based sclerotherapy,
and 4 trials compared endoscopic band ligation
⚬ mean follow-up was 16.3 months (range 6-26 months)
⚬ comparing cyanoacrylate to band ligation
– cyanoacrylate associated with decreased rebleeding in analysis of 4 trials with 360 patients (2 of
these trials included below)
● risk ratio 0.6 (95% CI 0.41-0.88)
● NNT 6-28 with rebleeding in 30% of band ligation group
● bleeding-related mortality in analysis of 4 trials with 365 patients

● treatment failure in analysis of 4 trials with 264 patients
● adverse e ects in analysis of 3 trials with 307 patients, results limited by signi cant
heterogeneity
⚬ comparing cyanoacrylate 0.5 mL plus Lipiodol 1.3 mL vs. cyanoacrylate 1 mL plus Lipiodol 1.8 mL in
1 trial with 91 patients
– fever in 27.3% vs. 48.9% (p = 0.042, NNT 5)
– no signi cant di erence in 30-day mortality, treatment failure, or rebleeding
⚬ Reference - Cochrane Database Syst Rev 2015 May 12;(5):CD010180
⚬ endoscopic N-butyl-2-cyanoacrylate injection reduces rebleeding and recurrence rates

compared to endoscopic band ligation for gastric variceal hemorrhage
DynaMed Level 1
– based on randomized trial

– 115 cirrhotic patients aged 18-80 years with cirrhosis and endoscopically con rmed gastric
variceal hemorrhage were randomized to endoscopic injection of cyanoacrylate 0.5 mL plus
Lipiodol 0.5 mL (≤ 6 shots per session) vs. endoscopic ligation (≤ 10 bands per session)
● patients were treated with vasoactive drugs (terlipressin or somatostatin) before diagnostic
endoscopy
● immediately after endoscopic treatment patients received omeprazole 40 mg IV every 12
hours for 2 days, then omeprazole 20 mg orally twice daily for 12 days
● endoscopic treatments performed every 3-4 weeks until varices eradicated
● concomitant esophageal varices subsequently ligated in both groups after eradication of
gastric varices
– follow-up endoscopy performed every 3 months until unremarkable twice, then every 6 months
until death or 6 months after last patient enrolled
– 18 patients (15.7%) excluded from analysis after randomization because diagnosis found to
meet exclusion criteria
– comparing cyanoacrylate injection vs. ligation
● rebleeding in 22.5% vs. 43.8% (p = 0.044, NNT 5)

● eradication in 63.3% vs. 66.7% (not signi cant)
● recurrence rate (in 63 patients with eradication of gastric varices) 22.6% vs. 59.4% (p = 0.007,
NNT 3)
– in intention-to-treat analysis including 18 excluded patients, rebleeding in 18.6% with
cyanoacrylate injection vs. 37.5% with ligation (p = 0.041, NNT 6)
– no signi cant di erences in control of active bleeding, number of sessions, days to eradicate
varices, complications, 30-day mortality, or cause of mortality
– Reference - Hepatology 2006 Apr;43(4):690 , correction can be found in Hepatology 2006
Jun;43(6):1410
⚬ endoscopic cyanoacrylate injection associated with lower rebleeding rate and mortality
compared to endoscopic band ligation for bleeding gastric varices
DynaMed Level 2
– based on small randomized trial with early trial termination

– 60 patients aged 20-70 years (77% male) with cirrhosis and gastric variceal bleeding were
randomized to gastric variceal obturation (n-butyl-2-cyanoacrylate [Histoacryl] plus lipiodol) vs.
gastric variceal band ligation (1-4 rubber bands per session)
● concomitant esophageal varices were treated with endoscopic variceal ligation immediately
after treatment of gastric varices in both groups
● treatment repeated every 3-4 weeks until obliteration of gastric varices
– trial terminated early without stopping rule after 3 years when signi cant di erences were
found at interim analysis
– 15 patients with cyanoacrylate and 11 patients with band ligation had active bleeding at
treatment
– comparing cyanoacrylate vs. band ligation
● initial hemostasis (no bleeding for rst 72 hours in active bleeders) achieved in 87% vs. 45%
(p = 0.03, NNT 3)
● obliteration of gastric varices in 51% vs. 45% (not signi cant)
● rebleeding in 31% vs. 54% (p = 0.0005, NNT 5)
● treatment failure in 13% vs. 38% (p < 0.05, NNT 4)
● treatment-induced ulcer bleeding in 7% vs. 28% (p = 0.03, NNT 5)
● mortality 29% vs. 48% (p = 0.05, NNT 6)
● gastric variceal bleeding-associated mortality 6% vs. 24% (p = 0.07)
– Reference - Hepatology 2001 May;33(5):1060 , commentary can be found in Hepatology 2002

Nov;36(5):1298
STUDY
● SUMMARY
cyanoacrylate injection may be associated with increased control of active bleeding, but similar
rates for rebleeding compared to endoscopic sclerotherapy DynaMed Level 2
RANDOMIZED TRIAL: BMC Gastroenterol 2019 Feb 4;19(1):23 | Full Text
Details
⚬ 113 patients with cirrhosis and actively bleeding esophageal varices were randomized to
cyanoacrylate injection vs. endoscopic sclerotherapy
⚬ patients were followed up every 2 weeks for 6 weeks
⚬ control of active bleeding de ned as no hematemesis, stable hemodynamic status, and stable
hemoglobin concentration without blood transfusion for 24 hours following endoscopy
⚬ comparing cyanoacrylate injection vs. sclerotherapy
– control of active bleeding in 98,3% vs. 83.9% (p = 0.007)

– rebleeding in 19.3% vs. 26.8% (not signi cant)
⚬ no signi cant di erences in mortality, complications, or hospital stay

⚬ Reference - BMC Gastroenterol 2019 Feb 4;19(1):23 full-text
Balloon-occluded retrograde transvenous obliteration (BRTO)
● BRTO involves using balloon to occlude out ow veins of portosystemic shunt, then endovascularly
injecting sclerosing agent into varix
⚬ main advantage is preservation of hepatic ow, reducing risk of hepatic encephalopathy compared
to TIPS
⚬ patients with coagulopathy and high Model of End Stage Liver Disease (MELD) scores may also
bene t from BRTO over TIPS
⚬ may transiently increase portal pressure, aggravating esophageal varices and increasing risk of
ascites
⚬ Reference - J Gastrointestin Liver Dis 2016 Mar;25(1):115 PDF
STUDY
● SUMMARY
balloon-occluded retrograde transvenous obliteration reported to have 97% clinical success rate
in patients with acute bleeding or at-risk gastric varices DynaMed Level 3
SYSTEMATIC REVIEW: Dig Dis Sci 2015 Jun;60(6):1543
Details
⚬ based on systematic review of case series
⚬ systematic review of 24 case series evaluating balloon-occluded retrograde transvenous
obliteration in 1,016 patients with acute bleeding or at-risk gastric varices
⚬ most patients received ethanolamine oleate as sclerosing agent
⚬ 23 studies conducted in Asia, 1 study conducted in United States
⚬ clinical success de ned as no recurrence or rebleeding of gastric varices or complete obliteration of
varices on subsequent imaging
⚬ balloon-occluded retrograde transvenous obliteration had
– clinical success in 97.3% (95% CI 95.2%-98.8%) in analysis of 23 studies

– major complications in 2.6% (95% CI 1.1%-4.6%) in analysis of 23 studies
– esophageal variceal recurrence in 33.3% (95% CI 24.6%-42.6%) in analysis of 20 studies
⚬ Reference - Dig Dis Sci 2015 Jun;60(6):1543
STUDY
● SUMMARY
BRTO associated with high degree of variceal obliteration without recurrence but also
exacerbation of esophageal varices in patients with gastric varices
COHORT STUDY: J Gastroenterol Hepatol 2016 Nov;31(11):1844
Details
⚬ 154 patients (median age 65 years [range 34-86 years], 58.4% male) with gastric fundal varices with
current (57 patients) or high risk for (97 patients) hemorrhage, treated with BRTO evaluated for
outcome over median follow-up of 30 months (range 1-163 months)
⚬ BRTO technical success (gastric varices [GV] obliteration) in 95.5% (147 patients) with no recurrence
over follow-up
⚬ cumulative rates of survival
– at 1 year - 91%
– at 3 years - 76%
– at 5 years - 72%
– at 7 years - 66%
⚬ cumulative rates of esophageal variceal exacerbation
– at 1 year - 13%
– at 3 years - 20%
– at 5 years - 27%
– at 7 years - 35%
⚬ no signi cant di erence in survival rates between patients with BRTO for active hemorrhage and
prophylactic BRTO for patients at high risk of hemorrhage
⚬ Reference - J Gastroenterol Hepatol 2016 Nov;31(11):1844
STUDY
● SUMMARY
balloon-occluded retrograde transvenous obliteration may reduce 1-year rebleeding compared to
cyanoacrylate glue injection in patients with cardiofundal gastric variceal hemorrhage (GOV 2 or
IGV 1) DynaMed Level 2
COHORT STUDY: J Vasc Interv Radiol 2019 Feb;30(2):187
Details
⚬ 161 adults with portal hypertension and endoscopically con rmed cardiofundal gastric variceal
hemorrhage (GOV 2 or IGV 1) were treated with BRTO (using sodium tetradecyl sulfate) or
endoscopic N-butyl-2-cyanoacrylate glue injection
– 71 patients had BRTO, 90 patients had cyanoacrylate injection
– 20 patients with BRTO and 1 patient with cyanoacrylate injection had previous or simultaneous
transjugular intrahepatic portosystemic shunt (TIPS)
⚬ median follow-up 385 days for BRTO and 521 days for cyanoacrylate injection
⚬ 1-year rebleeding in 3.5% with BRTO vs. 22% with cyanoacrylate injection (p < 0.01)
⚬ no signi cant di erence in mortality or 6-week rebleeding rate
⚬ Reference - J Vasc Interv Radiol 2019 Feb;30(2):187
STUDY
● SUMMARY
transcatheter sclerotherapy (primarily with BRTO) may be associated with less bleeding and
higher survival than TIPS, especially in patients with Child-Pugh class A cirrhosis
DynaMed Level 2
COHORT STUDY: AJR Am J Roentgenol 2004 Aug;183(2):369
Details
⚬ 104 patients (mean age 59 years, 59% male) with cirrhosis and gastric varices with acute bleeding
or in danger of rupture were treated with endovascular treatment with transcatheter sclerotherapy
or transjugular intrahepatic portosystemic shunt (TIPS)
⚬ of 77 patients treated with transcatheter sclerotherapy, 64% had BRTO and 36% had percutaneous
transhepatic sclerotherapy
⚬ mean follow-up duration was 26.9 months with transcatheter sclerotherapy and 41.2 months with
TIPS
⚬ comparing transcatheter sclerotherapy vs. TIPS
– bleeding at 1 year in 2% vs. 20% (p < 0.01)

– 1-year survival 96% vs. 81% (p < 0.01)
– death due to hepatic failure in 4% vs. 37% (p < 0.01)
– death due to variceal bleeding in 4% vs. 7% (not signi cant)
⚬ signi cant di erences in survival were found in subgroup of 61 patients with Child-Pugh class A,
but not in subgroup of 43 patient with Child-Pugh class B or C
⚬ Reference - AJR Am J Roentgenol 2004 Aug;183(2):369
STUDY
● SUMMARY
vascular plug-assisted retrograde transvenous obliteration (PARTO) may be associated with
decreased procedural pain compared to BRTO with ethanolamine oleate (EO) and decreased
procedural time compared to BRTO, but may be associated with increased variceal recurrence
compared to BRTO in patients with portal hypertension and gastric variceal hemorrhage
DynaMed Level 2
COHORT STUDY: Cardiovasc Intervent Radiol 2016 Jun;39(6):840
Details
⚬ 95 patients (mean age 63 years) with portal hypertension and bleeding gastric varices had 1 of 3
procedures and were followed for 1 year
– 21 patients had vascular plug-assisted retrograde transvenous obliteration (PARTO)
– 49 patients had balloon-occluded retrograde transvenous obliteration (BRTO) with 5%
ethanolamine oleate (EO)
– 25 patients had BRTO with 3% sodium tetradecyl sulfate (STS)
⚬ 94.7% technical (variceal obliteration on computerized tomography) and clinical (cessation of

bleeding on endoscopy) success
⚬ procedure-related abdominal pain in (p < 0.05, pairwise comparisons not reported)
– 0% with PARTO
– 34.7% with BRTO with EO
– 0% with BRTO with STS foam
⚬ mean procedure time
– 20 minutes with PARTO (p < 0.017 vs. either BRTO procedure)

– 139.7 minutes with BRTO with EO
– 114.8 with BRTO with STS foam
⚬ expected 2-year recurrence rate
– 55.2% with PARTO (p < 0.05 vs. either BRTO procedure)

– 16.5% with BRTO with EO
– 0% with BRTO with STS foam
⚬ Reference - Cardiovasc Intervent Radiol 2016 Jun;39(6):840
STUDY
● SUMMARY
ethanolamine oleate and sodium tetradecyl sulfate appear equally effective as sclerosing agents
for BRTO in patients with bleeding gastric varices DynaMed Level 2
COHORT STUDY: Cardiovasc Intervent Radiol 2018 Apr;41(4):578

Details
⚬ 142 patients with bleeding gastric varices had BRTO with 5% ethanolamine oleate (EO) or 3%
sodium tetradecyl sulfate (STS) as sclerosing agent
⚬ 59 patients had BRTO with EO and 83 patients had BRTO with STS
⚬ median follow-up 24 months for BRTO with EO, 20 months for BRTO with STS
⚬ no signi cant di erences in technical success (obliteration of varix at rst follow-up CT), clinical
success (bleeding control and absence of rebleeding on endoscopy during follow-up), or 5-year
recurrence (recanalization of gastric varices after technical success)
⚬ Reference - Cardiovasc Intervent Radiol 2018 Apr;41(4):578
● see Gastric Varices for additional information
Bridge Therapy
Balloon tamponade
● balloon tamponade (Sengstaken-Blakemore for esophageal varices or Linton for both esophageal and
gastric varices) may be used as bridge to more de nitive therapy in patients with unstable disease 2
⚬ controls bleeding in approximately 80% of patients, but rebleeding often occurs after balloon
de ation
⚬ frequent complications include aspiration, migration, esophageal necrosis and perforation, and
death
⚬ keep balloon in place for < 24 hours to reduce complications
● American Association for the Study of Liver Diseases suggests balloon tamponade be used
temporarily (≤ 24 hours) for uncontrollable bleeding until more de nitive therapy (such as
transjugular intrahepatic portosystemic shunt [TIPS] or endoscopic therapy) can be performed 1
● Baveno VI international workshop consensus recommendations on balloon tamponade (Baveno Level
5, Grade D) 3
⚬ associated with high incidence of severe adverse events
⚬ reserve for cases of refractory esophageal bleeding
⚬ use temporarily (maximum 24 hours) until de nitive treatment can be started
⚬ provide intensive care unit monitoring
STUDY
● SUMMARY
balloon tamponade reported to result in 19.8% initial failure rate and 30.9% short-term
mortality in patients with cirrhosis and variceal bleeding DynaMed Level 3
SYSTEMATIC REVIEW: Semin Liver Dis 2019 May;39(2):178
Details
⚬ based on systematic review without direct comparisons
⚬ systematic review of 23 studies evaluating balloon tamponade or esophageal stents as bridge
therapy in patients with cirrhosis and active, massive, or refractory variceal bleeding
⚬ 12 studies evaluated balloon tamponade in 570 patients
⚬ pooled outcomes with balloon tamponade
– 19.8% initial failure to achieve 24-hour hemostasis
– 35.5% early failure to control bleeding within 2-15 days
– 43% short-term (5-day within hospital) failure
– 30.9% short-term mortality
– 53.4% medium-term (6-week or 30-day) failure
– 31.5% medium-term mortality
– 9.7% major adverse events resulting in death
⚬ Reference - Semin Liver Dis 2019 May;39(2):178
STUDY
● SUMMARY
in patients with acute variceal hemorrhage, use of balloon tamponade resulted in 41% 1-year
survival, and of those surviving to discharge 71% required TIPS DynaMed Level 3
CASE SERIES: Am J Emerg Med 2017 Oct;35(10):1500
Details
⚬ based on case series
⚬ 34 patients (median age 57 years) with acute variceal hemorrhage had balloon tamponade
⚬ 2 patients lost to follow-up
⚬ reported survival was
– 20 patients (59%) survived to hospital discharge

– 13 patients (41%) survived at 1 year
⚬ transjugular intrahepatic portosystemic shunt (TIPS) after balloon tamponade reported in
– 24 patients (71%) overall

– 95% of patients surviving to discharge compared to 36% of patients with in-hospital death (p <
0.01)
– 100% of patients with survival at 1 year
⚬ Reference - Am J Emerg Med 2017 Oct;35(10):1500
Self-expandable metal stents
● self-expandable metal stents may also be used as bridge therapy in patients with uncontrolled
esophageal bleeding and may have fewer complications than balloon tamponade 2
● Baveno VI international workshop consensus suggests self-expanding covered esophageal metal

stents may be as e ective as and safer than balloon tamponade for refractory esophageal variceal
bleeding (Baveno Level 4, Grade C) 3
STUDY
● SUMMARY
self-expandable covered metal stents might reduce continued bleeding with fewer serious
adverse events compared to balloon tamponade in patients with cirrhosis and refractory acute
esophageal variceal bleeding DynaMed Level 2
RANDOMIZED TRIAL: Hepatology 2016 Jun;63(6):1957
Details
⚬ based on small randomized trial with baseline and de nitive treatment di erences
⚬ 28 patients with cirrhosis and acute esophageal variceal bleeding refractory to medical and
endoscopic treatment were randomized to self-expandable covered metal stents (SX-ELLA Danis
stents) vs. balloon tamponade (Sengstaken-Blakemore tube)
⚬ all patients received vasoactive medication, prophylactic antibiotics, and endoscopic band ligation
⚬ median age 69 years with self-expanding stent vs. 54 years with balloon tamponade (p = 0.04)
⚬ treatment di erences comparing self-expanding stent vs. balloon tamponade
– de nitive treatment (p = 0.015)
● transjugular intrahepatic portosystemic shunt (TIPS) in 31% vs. 67%

● esophageal band ligation plus beta blockers in 39% vs. 0%
– median time on vasoactive drugs 6 days vs. 3 days (p = 0.002)

– severe hepatic encephalopathy after inclusion 39% vs. 73% (p = 0.063)
⚬ primary endpoint was composite of no bleeding, no serious adverse events, and survival at 15 days
⚬ comparing self-expanding stent vs. balloon tamponade
– primary endpoint in 66% vs. 20% (p = 0.025, NNT 3)

– no continued bleeding or rebleeding at day 15 in 85% vs. 47% (p = 0.037, NNT 3)
– no serious adverse events at day 15 in 84% vs. 53% (p = 0.077)
– 15-day survival 69% vs. 47% (not signi cant)
– rebleeding at 6 weeks in 54% vs. 47% (not signi cant)
– 6-week survival in 54% vs. 40% (not signi cant)
– ≥ 1 device-related serious adverse event in 8% vs. 40% (p = 0.049, NNT 3)
⚬ Reference - Hepatology 2016 Jun;63(6):1957
STUDY
● SUMMARY
40% overall mortality and 18% failure to control bleeding reported with self-expanding metal
stents in patients with cirrhosis and severe or refractory esophageal variceal bleeding
DynaMed Level 3
SYSTEMATIC REVIEW: Aliment Pharmacol Ther 2015 Dec;42(11-12):1250
Details
⚬ based on systematic review of mostly case series
⚬ systematic review of 13 studies (12 case series and 1 small randomized trial) evaluating e cacy of
self-expanding metal stents (SEMS) in 146 patients with cirrhosis and severe or refractory
esophageal variceal bleeding
⚬ most studies evaluated SX-ELLA Danis stent
⚬ 95% had successful SEMS placement
⚬ pooled event rates with SEMS placement
– overall mortality 40% (95% CI 31%-49%) in analysis of all studies

– 30-day mortality 36% (95% CI 26%-47%) in analysis of 11 studies with 120 patients
– failure to control bleeding in 18% (95% CI 11%-29%) in analysis of 12 studies with 134 patients
– stent migration in 28% (95% CI 17%-43%) in analysis of 11 studies with 131 patients
⚬ Reference - Aliment Pharmacol Ther 2015 Dec;42(11-12):1250
STUDY
● SUMMARY
esophageal stenting reported to result in 10.3% initial failure rate and 21.3% short-term
mortality in patients with cirrhosis and variceal bleeding DynaMed Level 3
SYSTEMATIC REVIEW: Semin Liver Dis 2019 May;39(2):178

Details
⚬ based on systematic review of mostly case series
⚬ systematic review of 23 studies (mostly case series) evaluating balloon tamponade or esophageal
stents as bridge therapy in patients with cirrhosis and active, massive, or refractory variceal
bleeding
⚬ 11 studies evaluated balloon tamponade in 188 patients
⚬ pooled outcomes with esophageal stents
– 10.3% initial failure to achieve 24-hour hemostasis

– 12.7% short-term (5-day within hospital) failure
– 21.3% short-term mortality
– 21% medium-term (6-week or 30-day) failure
– 41.8% medium-term mortality
⚬ Reference - Semin Liver Dis 2019 May;39(2):178
Shunting Procedures
Transjugular intrahepatic portosystemic shunts (TIPS)
General information
● TIPS reduces elevated portal pressure by creating communication between hepatic vein and
intrahepatic branch of portal vein (Liver Int 2017 Jan;37 Suppl 1:104 )
● may be used as salvage therapy in patients with 2
⚬ esophageal or gastric variceal bleeding not adequately controlled by medical or endoscopic

therapy
⚬ recurrent esophageal variceal bleeding after 2 endoscopic treatment
⚬ recurrent gastric variceal bleeding after 1 endoscopic treatment
● produces hemostasis in > 90% of cases and survival may be as high as 90% in absence of aspiration
pneumonia (Med Clin North Am 2008 May;92(3):551 )
● if aspiration pneumonia and multiorgan failure have occurred due to bleeding, prognosis is poor even
if hemostasis achieved 2
● contraindications to TIPS include
⚬ absolute
– congestive heart failure

– severe pulmonary hypertension
– tricuspid regurgitation
⚬ relative
– recurrent episodes of hepatic encephalopathy

– portal vein thrombosis
– hepatocellular carcinoma
⚬ Reference - Liver Int 2017 Jan;37 Suppl 1:104
● review of TIPS for gastrointestinal variceal bleeding can be found in Diagn Interv Imaging 2015 Jul-
Aug;96(7-8):745
IMAGE 1 OF 1
Fluoroscopic image of TIPS in progress
A catheter (black arrow) has been passed into the hepatic

vein and after needle puncture, a guide wire (white arrow)
was passed into the portal vein to allow transhepatic access
to locate and opacify the portal vein. A self-expandable
metallic stent has not yet been placed. Abbreviation: TIPS,
transjugular intrahepatic portosystemic shunt.
Recommendations for use from professional organizations
● Baveno VI international workshop consensus recommendations on TIPS 3
⚬ strongly consider TIPS placement early in patients with esophageal varices, gastroesophageal
varices type 1, or gastroesophageal varices type 2 who are at high risk of treatment failure (Baveno
Level 1b, Grade A)
– treat within 72 hours (ideally within 24 hours) after initial pharmacological and endoscopic
therapy
– high risk of treatment failure de ned as Child-Pugh Class C (< 14 points) or Child-Pugh Class B
with active bleeding
⚬ for management of treatment failure
– persistent bleeding despite combined pharmacologic and endoscopic therapy is best managed
by TIPS with polytetra uoroethylene (PTFE)-covered stents (Baveno Level 2b, Grade B)
– if rebleeding during rst 5 days, consider second attempt at endoscopic therapy; if severe
rebleeding, PTFE-covered TIPS is likely best option (Baveno Level 2b, Grade B)
● American Association for the Study of Liver Diseases (AASLD) guideline on role of TIPS in management
of portal hypertension 1
⚬ TIPS is e ective for controlling acute bleeding from varices refractory to medical therapy and is
preferred to surgery (AASLD Grade II-3)
⚬ TIPS should not be used for prevention of rebleeding in patients who have bled only once from
esophageal varices, limit use to patients who fail pharmacologic and endoscopic therapy (AASLD
Grade I)
⚬ TIPS is e ective for prevention of rebleeding from gastric and ectopic varices (including intestinal,
stomal, and anorectal varices) and is preferred approach (AASLD Grade II-3)
⚬ for patients with portal hypertensive gastropathy, limit use of TIPS to patients who have recurrent
bleeding with beta blocker use (AASLD Grade II-3)
⚬ TIPS is not e ective and should not be used for controlling bleeding from gastric antral vascular
ectasia (GAVE) in patients with cirrhosis (AASLD Grade II-3)
⚬ choosing TIPS for prevention of rebleeding
– for patients with good liver function, TIPS or surgical shunt are appropriate choices for
prevention of rebleeding in patients who failed medical therapy (AASLD Grade I)
– for patients with poor liver function, TIPS preferred over surgery for prevention of rebleeding in
patients who failed medical therapy (AASLD Grade III)
– for information on prevention of rebleeding see Esophageal Variceal Hemorrhage - Prevention
of Rebleeding
⚬ Reference - Hepatology 2010 Jan;51(1):306 , commentary can be found in Hepatology 2010
Jun;51(6):2236
Efficacy
STUDY
● SUMMARY
TIPS with bare stent reduces rebleeding but increases rate of hepatic encephalopathy compared
to cyanoacrylate injection in patients with bleeding of gastric varices DynaMed Level 1
RANDOMIZED TRIAL: Endoscopy 2007 Aug;39(8):679
Details
⚬ 74 patients aged 20-75 years with cirrhosis hospitalized for acute gastric variceal bleeding were
randomized after emergency treatment maintained hemostasis for > 72 hours to TIPS with bare
stents vs. endoscopic injection of N-butyl-2-cyanoacrylate
– all patients received immediate resuscitation and somatostatin on admission
– endoscopy was performed within 24 hours and all patients with gastric variceal bleeding
received cyanoacrylate injection
– patients randomized to cyanoacrylate had endoscopic obturation every 4 weeks until
obliteration
⚬ 2 patients randomized to TIPS refused intervention and were excluded from analysis
⚬ history of prior esophagogastric variceal bleeding in 57% with TIPS vs. 30% with cyanoacrylate (p =
0.02)
⚬ median follow-up was 33 months with TIPS and 32 months with cyanoacrylate
⚬ insertion of stent shunt successful in all patients receiving TIPS - mean portal pressure gradient
decreased from 21.4 mm Hg to 7.5 mm Hg after TIPS insertion (p < 0.001)
⚬ comparing TIPS vs. cyanoacrylate
– obliteration of gastric varices in 20% vs. 51% (p < 0.02)

– signi cant rebleeding from gastric varices in 11% vs. 38% (p = 0.014, NNT 4)
– rebleeding from either esophageal or gastric varices in 20% vs. 51% (p < 0.04, NNT 4)
– upper gastrointestinal bleeding in 43% vs. 59% (p = 0.12)
– treatment failure in 3% vs. 8% (not signi cant)
– hepatic encephalopathy in 26% vs. 3% (p < 0.01, NNH 4)
⚬ no signi cant di erence in survival time or mortality

⚬ TIPS stent occlusion
– stenosis or stent occlusion in 8 patients (23%), 6 patients had revision

– TIPS dysfunction observed in 5 of 7 patients with bleeding esophageal or gastric varices
⚬ Reference - Endoscopy 2007 Aug;39(8):679 , commentary can be found in Endoscopy 2008

Feb;40(2):168 , Endoscopy 2008 May;40(5):448
⚬
DynaMed Commentary
Bare stents were used in this study. Results are not applicable to TIPS using
polytetra uoroethylene (PTFE)-covered stents, which have been associated with better stent
patency and less TIPS dysfunction than bare stents.
STUDY
● SUMMARY
in patients having transjugular intrahepatic portosystemic shunt, use of left branch of the portal
vein for a puncture site may be associated with fewer complications than intrahepatic
bifurcation of the portal vein or right branch or the portal vein DynaMed Level 2
COHORT STUDY: Gastroenterol Res Pract 2019;2019:2935498
Details
⚬ 171 patients who had transjugular intrahepatic portosystemic shunt (TIPS) were divided into 3
groups based on puncture site
– 88 intrahepatic bifurcation of the portal vein
– 48 right branch of the portal vein
– 35 left branch of the portal vein
⚬ indications for TIPS included symptomatic portal hypertension, repeated variceal bleeding, and
refractory ascites
⚬ mean follow-up 47 months (range 6-104 months)
⚬ shunt stenosis in (p = 0.001, pairwise comparisons not reported)
– 38.6% with intrahepatic bifurcation of the portal vein

– 29.2% with right branch of the portal vein
– 8.6% with left branch of the portal vein
⚬ hepatic encephalopathy in (p = 0.006, pairwise comparisons not reported)
– 35.2% with intrahepatic bifurcation of the portal vein

– 39.6% with right branch of the portal vein
– 11.4% with left branch of the portal vein
⚬ Reference - Gastroenterol Res Pract 2019;2019:2935498
EVIDENCE SYNOPSIS
Early TIPS increases survival and reduces treatment failures, rebleeding, or ascites in patients with
acute variceal bleeding in Child-Pugh C patients at high risk of treatment failure compared with
standard endoscopic and medical therapy. Con icting evidence exists on mortality in Child-Pugh B
patients with active bleeding.
STUDY
⚬ SUMMARY
TIPS increases survival and reduces treatment failure compared to medical or endoscopic
therapy in patients with cirrhosis and acute variceal bleeding DynaMed Level 1
J Clin Gastroenterol 2015 Jul;49(6):495

N Engl J Med 2010 Jun 24;362(25):2370
Details
– based on systematic review including high-quality study
– systematic review of 6 studies (3 randomized trials and 3 retrospective cohort studies)
comparing TIPS vs. medical or endoscopic therapy in 388 patients with cirrhosis and acute
variceal bleeding
● bleeding source was esophageal varices in 3 studies, gastric varices in 1 study, and mixed
esophageal and/or gastric varices in 2 studies
● 3 studies included only high-risk patients
● TIPS included bare stents in 2 studies, covered stents in 2 studies, and unknown stent type
in 2 studies
● control groups included medical therapy plus endoscopic sclerotherapy in 1 study, medical
therapy plus N-butyl-2-cyanoacrylate injection in 2 studies, and medial and/or endoscopic
therapy in 3 studies
– compared to medical or endoscopic therapy, TIPS associated with
● increased survival (hazard ratio for death 0.55, 95% CI 0.38-0.81) in analysis of all studies
● decreased treatment failure in analysis of 5 studies with 339 patients
⚬ odds ratio [OR] 0.22 (95% CI 0.11-0.44)

⚬ NNT 5-9 with treatment failure in 25% of control group
● decreased bleeding-related death in analysis of 4 studies with 296 patients
⚬ OR 0.19 (95% CI 0.06-0.59)

⚬ NNT 9-22 with bleeding-related death in 12% of control group
– no signi cant di erences in rebleeding in overall analysis of 5 studies including 336 patients,
but TIPS associated with reduced risk of rebleeding (OR 0.09, 95% CI 0.03-0.32) in analysis of 2
randomized trials with 112 patients analyzed after excluding nonrandomized studies
– no signi cant di erences in hepatic encephalopathy in analysis of 5 studies with 345 patients
with consistent results in analysis of 3 randomized trials
– Reference - J Clin Gastroenterol 2015 Jul;49(6):495
–
DynaMed Commentary
Analysis included at least 2 of 6 studies using bare stents, which may have poorer
outcomes than covered stents. These ndings may underestimate bene t from TIPS
intervention using polytetra uoroethylene (PTFE)-covered stents.
– consistent results in high-quality study and in subset of 4 randomized trials evaluating early
TIPS in patients with cirrhosis and acute variceal bleeding (Eur J Gastroenterol Hepatol 2015
Sep;27(9):e1 )
– early TIPS reduces mortality and treatment failure compared to continued drug and
endoscopic therapy in high-risk patients with cirrhosis and esophageal variceal bleeding
DynaMed Level 1
● based on randomized trial

● 63 patients (mean age 51 years, 70% male) with cirrhosis and acute esophageal variceal
bleeding previously treated with vasoactive drugs plus endoscopic therapy (endoscopic
band ligation or sclerotherapy) were randomized within 24 hours of admission to 1 of 2
treatments
⚬ TIPS with PTFE-covered stent performed ≤ 72 hours after diagnostic endoscopy
⚬ continued vasoactive drug therapy until free of bleeding for ≥ 24 hours or up to 5 days,
then treatment with nonselective beta blocker (propranolol or nadolol), isosorbide-5-
mononitrate, and repeat endoscopic band ligation
● all patients had Child-Pugh class C (score 10-13) cirrhosis or class B plus active bleeding at
diagnostic endoscopy
● during median 16-month follow-up
⚬ 11% were lost to follow-up

⚬ 9.5% had liver transplant
⚬ 22.5% randomized to continued drug therapy received TIPS as rescue treatment (57% of
whom died)
● comparing early TIPS vs. continued drug therapy
⚬ mortality 12.5% vs. 38.7% (p = 0.01, NNT 4)

⚬ treatment failure at 5 days (1 severe bleed or 2 less severe bleeding sessions) in 3.1% vs.
12.9% (no p value reported)
⚬ failure to control bleeding or rebleeding within 1 year in 3.1% vs. 45.1% (p = 0.001, NNT
3)
⚬ 6-week survival 97% vs. 67% (p < 0.05, NNT 4)
⚬ 1-year survival rate 86% vs. 61% (p < 0.05, NNT 4)
⚬ mean length of intensive care stay 3.6 days vs. 8.6 days (p = 0.01)
● no signi cant di erence in adverse events including hepatic encephalopathy

● Reference - N Engl J Med 2010 Jun 24;362(25):2370 , editorial can be found in N Engl J
Med 2010 Jun 24;362(25):2421 , commentary can be found in J Hepatol 2011
Nov;55(5):1148
STUDY
⚬ SUMMARY
early TIPS may reduce mortality and rebleeding in patients with esophageal variceal
bleeding and decompensated liver disease DynaMed Level 2
COHORT STUDY: J Gastroenterol Hepatol 2017 Apr;32(4):852
Details
– 142,539 patients (mean age 58 years, 68% male) with esophageal variceal bleeding and
decompensated liver disease admitted between 2000 and 2010 were treated with early
preventative TIPS (0.5%), rescue TIPS (4.1), or no TIPS (endoscopic ligation with medical
therapy, 99.4%)
● decompensated liver disease de ned as Baveno V classi cation 3 (upper gastrointestinal
bleeding without ascites) or 5 (ascites and bleeding)
● early TIPS de ned as TIPS within 3 days after hospitalization after 1
esophagogastroduodenoscopy with endoscopic therapy
● rescue TIPS de ned as TIPS after ≥ 2 interventions (of which ≥ 1 endoscopic with possible
non-endoscopic additional procedure)
– comparing early TIPS vs. no TIPS
● in-hospital mortality 1.5% vs. 5.6% (p < 0.01)

● in-hospital rebleeding in 0.5% vs. 15.4% (p < 0.01)
– no signi cant di erence in mean hospital length of stay, hepatic encephalopathy, or sepsis
– comparing early TIPS vs. rescue TIPS
● in-hospital mortality 1.5% vs. 8.1% (p < 0.01)

● in-hospital rebleeding in 0.5% vs. 2.2% (p < 0.01)
● mean hospital length of stay 5.1 days vs. 9.6 days (p < 0.01)
– no signi cant di erence in hepatic encephalopathy or sepsis

– Reference - J Gastroenterol Hepatol 2017 Apr;32(4):852
STUDY
⚬ SUMMARY
in patients with Child-Pugh Class C and high risk of treatment failure, early TIPS may
decrease 1-year mortality DynaMed Level 2
COHORT STUDY: Hepatology 2019 Jan;69(1):282
Details
– based on prospective cohort study
– 671 patients ≤ 75 years old with cirrhosis and acute variceal bleeding and high risk for
treatment failure from 34 academic medical centers in Europe and Canada were included
● high risk patients de ned as patients with Child-Pugh C or Child-Pugh B with active bleeding
on endoscopy
● all patients had standard care (vasoactive drugs, antibiotics, endoscopic therapy) as initial
treatment
● 66 patients (10%) had early TIPS (≤ 72 hours of diagnostic endoscopy), 605 patients (90%)
had continuing standard of care
– follow-up was 1 year and included 211 patients
– among patients with Child-Pugh Class C, 1-year mortality 22% with early TIPS vs. 47% with
standard care (p = 0.002, NNT 4)
– no signi cant di erence in 1-year mortality in patients with Child-Pugh B and active bleeding
or in risk of hepatic encephalopathy
– Reference - Hepatology 2019 Jan;69(1):282
STUDY
⚬ SUMMARY
early TIPS may decrease 1 year mortality in patients with Child-Pugh C but not Child-Pugh
B, and may decrease risk of treatment failure, rebleeding, and ascites in patients with
cirrhosis and acute variceal bleeding DynaMed Level 2
COHORT STUDY: Gut 2019 Jul;68(7):1297
Details
– 1,425 patients ≤ 75 years old with cirrhosis and acute variceal bleeding had either early TIPS (≤
72 hours of admission and prior to rebleeding) or continuing standard care
– median follow-up 22.9 months with early TIPS and 23.4 months with standard care
– comparing early TIPS vs. standard care at 1 year
● mortality at 6 weeks
⚬ overall 3.6% vs. 10.6% (p = 0.002)

⚬ in patients with Child-Pugh C 6.1% vs. 29.3% (p = 0.002)
⚬ in patients with Child-Pugh B 3.1% vs. 12.2% (p = 0.002)
● mortality at 1 year
⚬ overall 14.1% vs. 17.3% (not signi cant)

⚬ in patients with Child-Pugh C 24.2% vs. 44.6% (p = 0.021)
⚬ in patients with Child-Pugh B 17.5% vs. 19.7% (not signi cant)
● treatment failure or rebleeding at 1 year in 10.7% vs. 40.7% (p < 0.001)

● new or worsening ascites at 1 year in 5.2% vs. 11.9% (p = 0.021)
– no signi cant di erence in overt hepatic encephalopathy at 6 weeks or 1 year

– Reference - Gut 2019 Jul;68(7):1297
Stent type
STUDY
● SUMMARY
covered stents reduce stent dysfunction, but do not improve early complications or survival, in
patients with cirrhosis having TIPS DynaMed Level 1
RANDOMIZED TRIAL: J Hepatol 2014 May;60(5):962
Details
⚬ 137 patients with cirrhosis having TIPS were randomized to covered vs. bare stents
⚬ patients and outcome assessors were blinded
⚬ 94% were included in analysis; patients with hepatocellular carcinoma and with canceled
procedures were excluded
⚬ median follow-up was 23.6 months in covered stent group and 21.8 months in bare stent group
⚬ transjugular angiography scheduled for every 6 months after TIPS insertion, with stent dysfunction
de ned as portocaval gradient ≥ 12 mm Hg or stent lumen stenosis ≥ 50%
⚬ comparing covered vs. bare stents
– ≥ 1 episode of stent dysfunction at 2-years in 44% vs. 63.6% (p = 0.03, NNT 6)

– early TIPS complications in 22.4% vs. 34.9% (not signi cant)
– 2-year survival 70% vs. 67.5% (not signi cant)
⚬ no signi cant di erences in hepatic encephalopathy

⚬ Reference - J Hepatol 2014 May;60(5):962
STUDY
● SUMMARY
10-mm polytetrafluoroethylene covered stent may reduce risk of complications after TIPS
compared with 8-mm covered stent DynaMed Level 2
RANDOMIZED TRIAL: J Hepatol 2010 Aug;53(2):267
Details
⚬ based on small randomized trial with early termination
⚬ 45 patients with variceal bleeding or refractory ascites due to liver cirrhosis randomized to TIPS
created with 10-mm vs. 8-mm polytetra uoroethylene covered stent
⚬ trial terminated early due to signi cantly higher portosystemic pressure gradient in 8-mm stent
group
⚬ probability of remaining free of complications due to portal hypertension at 1 year was 82.9% with
10-mm stent vs. 41.9% with 8-mm stent (p = 0.002)
⚬ Reference - J Hepatol 2010 Aug;53(2):267
Assessing patency of TIPS
STUDY
● SUMMARY
Doppler ultrasound may help rule out transjugular intrahepatic portosystemic shunt (TIPS)
dysfunction in patients with stent-graft TIPS
DIAGNOSTIC COHORT STUDY: J Clin Imaging Sci 2016;6:29 | Full Text
Details
⚬ based on retrospective diagnostic cohort study
⚬ 41 patients (median age 55 years, 73% male) with stent-graft TIPS had 52 evaluations with paired
Doppler ultrasound and TIPS venography
– patients were symptomatic during 77% of evaluations (recurrent or persistent ascites or
hydrothorax or recurrent variceal bleeding)
– median time to between Doppler ultrasound and TIPS venography was 3 days
⚬ 38% had TIPS dysfunction by venography (reference standard)

⚬ 64% of evaluations (26 patients) had Doppler ultrasound abnormalities de ned as TIPS velocity >
190 cm/second or < 90 cm/second, temporal alterations in TIPS velocity > 50 cm/second since prior
Doppler ultrasound, absent shunt ow, or antegrade intrahepatic portal ow
⚬ concordance with TIPS venography was 65% for Doppler ultrasound, 48% for clinical exam, and
60% for Doppler ultrasound plus clinical exam
⚬ for diagnosis of TIPS dysfunction
– Doppler ultrasound had sensitivity 85% and speci city 50%

– clinical exam had sensitivity 80% and speci city 25%
⚬ in subgroup analysis of 43 examinations in 35 patients with paired Doppler ultrasound and

venography performed within 14 days, sensitivity of Doppler ultrasound increased to 100%, but
speci city remained low
⚬ Reference - J Clin Imaging Sci 2016;6:29 full-text
STUDY
● SUMMARY
Doppler ultrasound evaluations may help detect TIPS dysfunction, but different parameters may
need to be assessed for covered and bare metal stents DynaMed Level 2
DIAGNOSTIC COHORT STUDY: AJR Am J Roentgenol 2013 Apr;200(4):904
Details
⚬ based on retrospective diagnostic cohort study without independent validation
⚬ 78 patients with TIPS had 126 paired evaluations by Doppler ultrasound followed by angiography
(reference standard) within 60 days
– 23 patients (mean age 57 years, 74% male) had 43 evaluations of bare metal stents and 55
patients (mean age 55 years, 76% male) had 83 evaluations of covered stents
– 52.3% of bare metal stent evaluations and 60.7% of covered stent evaluations showed
dysfunction on angiography
⚬ performance of Doppler ultrasound for diagnosis of TIPS dysfunction
Table 3. Impact of Stent Type on Diagnostic Performance of Doppler Ultrasound
for TIPS Dysfunction
Bare Metal Covered
Sensitivity Speci city Sensitivity Speci city
Peak shunt 77.3% 35% 76.5% 42.4%

velocity with
cuto < 90
cm/second
or > 200
cm/second
Maximum 36.4% 80%* 33.3% 48.5%

peak shunt
velocity with
cuto > 200
cm/second
Minimum 40.9% 55% 43.1% 93.9%**

peak shunt
velocity with
cuto < 90
cm/second
Change in 40% 57.1% 81.5%** 33.3%

peak shunt
velocity >
25%
Abbreviation: TIPS, transjugular intrahepatic

portosystemic shunt.
* p < 0.05 compared to

covered stent.
** p < 0.05 compared to bare

metal stent.
⚬ Reference - AJR Am J Roentgenol 2013 Apr;200(4):904
Portacaval shunt
● portal-systemic shunts have been used infrequently to control variceal bleeding or prevent rebleeding
due to concerns of increased risk of portal-systemic encephalopathy and liver failure with their use,
but evidence may not support these concerns
⚬ portacaval shunts for emergency treatment of bleeding esophageal varices associated with prompt
control of bleeding and increased survival compared to transjugular intrahepatic portosystemic
shunt (TIPS) or endoscopic therapy, and not associated with increased encephalopathy
⚬ portacaval shunts also associated high rates of lifelong shunt patency
⚬ Reference - JAMA Surg 2014 Feb;149(2):155
STUDY
● SUMMARY
portacaval shunt may reduce rebleeding and improve survival compared to endoscopic therapy
in patients with cirrhosis and gastric variceal bleeding DynaMed Level 2
RANDOMIZED TRIAL: Surgery 2015 Jun;157(6):1028
Details
⚬ based on randomized trial with changes in endoscopic therapy protocol during trial
⚬ 518 patients (mean age 50 years, 65% male) with cirrhosis and endoscopy-con rmed gastric
variceal bleeding were randomized to portacaval shunt vs. endoscopic therapy from 1977 to 1997
– all patients had bleeding requiring blood transfusion ≥ 2 units before randomization
– endoscopic therapy included sclerotherapy from 1977-1990 and sclerotherapy or band ligation
from 1990 to 1997
⚬ 42.5% had emergency procedures and remaining patients had elective procedures
⚬ 97% had follow-up for > 10 years or until death
⚬ comparing portacaval shunt vs. endoscopic therapy
– in analysis of 220 emergency procedures
● initial control of bleeding in 97% vs. 82% (p < 0.001, NNT 7)

● 30-day bleeding control and in-hospital survival in 78% vs. 41% (p < 0.001, NNT 3)
● recurrent bleeding at any time in 2% vs. 73% (p < 0.001)
● 1-year survival 70% vs. 27% (p < 0.001, NNT 3)
● 10-year survival in 59% vs. 20% (p < 0.001, NNT 3)
– in analysis of 298 elective procedures
● recurrent bleeding at any time in 0.7% vs. 71% (p < 0.001, NNT 2)
● bleeding control up to 5 years or death in 99% vs. 29% (p < 0.001, NNT 2)
● 30-day survival and hospital release in 99% vs. 93% (p = 0.021, NNT 17)
– stent patency at 5-years was 99%
⚬ Reference - Surgery 2015 Jun;157(6):1028
STUDY
● SUMMARY
portacaval shunt reduces rebleeding and improves survival compared to TIPS in patients with
cirrhosis and gastric variceal bleeding DynaMed Level 1
RANDOMIZED TRIAL: Surgery 2015 Jun;157(6):1028
Details
⚬ 70 patients (70% male) with cirrhosis and endoscopy-con rmed gastric variceal bleeding were
randomized to emergency portacaval shunt vs. emergency TIPS from 1997 to 2011
⚬ all patients had bleeding requiring blood transfusion ≥ 2 units before randomization
⚬ comparing emergency portacaval shunt vs. emergency TIPS
– initial control of bleeding in 100% vs. 83% (p < 0.001, NNT 6)

– 30-day bleeding control and in-hospital survival in 85% vs. 56% (p < 0.001, NNT 4)
– recurrent bleeding at any time in 0% vs. 94% (p < 0.001, NNT 1)
– 1-year survival 85% vs. 50% (p < 0.001, NNT 3)
– 5-year stent patency in 100% vs. 33% (p < 0.001, NNT 2)
⚬ Reference - Surgery 2015 Jun;157(6):1028
STUDY
● SUMMARY
emergency portacaval shunt may increase bleeding control and survival compared to endoscopic
sclerotherapy in patients with cirrhosis and acutely bleeding esophageal varices
DynaMed Level 2
RANDOMIZED TRIAL: J Am Coll Surg 2009 Jul;209(1):25
Details
⚬ based on randomized trial with baseline di erences
⚬ 211 patients (mean age 48 years, 77% male) with cirrhosis and acutely bleeding esophageal varices
requiring ≥ 2 units of blood transfusion were randomized to emergency portacaval shunt vs.
endoscopic sclerotherapy within 8 hours
⚬ 96% were followed for > 10 years or until death
⚬ baseline di erences comparing portacaval shunt vs. endoscopic sclerotherapy
– history of ascites in 46% vs. 66% (p = 0.004)

– type 2 diabetes in 23% vs. 12% (p = 0.047)
– renal disease in 10% vs. 3% (p = 0.049)
– severe muscle wasting in 64% vs. 47% (p = 0.026)
⚬ e cacy outcomes comparing portacaval shunt vs. endoscopic sclerotherapy

– control of bleeding for > 30 days in 100% vs. 20% (p < 0.001, NNT 2)
– treatment failure in 0% vs. 79% (p < 0.001, NNT 2)
– 30-day survival 87% vs. 88% (not signi cant)
– mean total packed red blood cell units during index hospitalization 15 vs. 10 (p < 0.001)
– recurrent portal-systemic encephalopathy in 15% vs. 35% (p < 0.001, NNT 4)
⚬ Reference - J Am Coll Surg 2009 Jul;209(1):25
STUDY
● SUMMARY
small-diameter prosthetic H-graft portacaval shunt associated with longer time to shunt failure
than TIPS in patients with portal hypertension due to cirrhosis, and longer survival in patients
with Child-Pugh class A or B cirrhosis but higher mortality in patients with Child-Pugh class C
cirrhosis DynaMed Level 2
RANDOMIZED TRIAL: J Am Coll Surg 2012 Apr;214(4):445

Details
⚬ based on follow-up study and subgroup analysis of randomized trial without blinding
⚬ 132 patients (mean age 55 years, 70% male) with portal hypertension due to cirrhosis and bleeding
esophagogastric varices or hypertensive gastropathy were randomized to small-diameter
prosthetic H-graft portacaval shunt vs. transjugular intrahepatic portosystemic shunt (TIPS) and
followed for up to 18 years
⚬ all patients had failed or were unamenable to endoscopic therapy
⚬ shunt failure occurred in 88% in both groups
⚬ comparing portacaval shunt vs. TIPS
– 30-day mortality 20% vs. 15% (no p value reported)

– mean time to shunt failure 42 months vs. 19 months (p = 0.04)
– variceal rehemorrhage in 7.6% vs. 30% (p < 0.05, NNT 5)
– shunt stenosis and/or thrombosis in 11% vs. 48% (p < 0.05, NNT 3)
– liver transplant in 2% vs. 11% (p < 0.05, NNT 12)
– overall mortality 88% vs. 88% (not signi cant)
⚬ median overall survival comparing portacaval shunt vs. TIPS in subgroup analyses
– 91 months vs. 19 months in analysis of 21 patients with Child-Pugh class A cirrhosis (p = 0.009)
– 63 months vs. 21 months in analysis of 49 patients with Child-Pugh class B cirrhosis (p = 0.002)
– 22 months vs. 45 months in analysis of 62 patients with Child-Pugh class C cirrhosis (p = 0.04)
⚬ Reference - J Am Coll Surg 2012 Apr;214(4):445

⚬ consistent results for decreased harms (less rebleeding, shunt occlusion, encephalopathy, need for
reintervention, and improved 5 year survival) found in systematic review of 4 trials with 496
patients but con dence in ndings limited by low certainty of evidence and high risk of random
errors (Cochrane Database Syst Rev 2018 Oct 31;10:CD001023 )
Other shunt procedures
STUDY
● SUMMARY
distal splenorenal shunt and transjugular intrahepatic portal systemic shunt may have similar
rates of rebleeding, encephalopathy, and survival in patients with cirrhosis and refractory
variceal bleeding DynaMed Level 2
RANDOMIZED TRIAL: Gastroenterology 2006 May;130(6):1643
Details
⚬ 140 patients with cirrhosis and refractory variceal bleeding randomized to distal splenorenal shunt
vs. transjugular intrahepatic portosystemic shunt (TIPS)
⚬ mean follow-up was 46 months (range 2-8 years)
⚬ comparing distal splenorenal shunt vs. TIPS (no signi cant di erences in any outcome)
– rebleeding in 5.5% vs. 10.5%

– rst encephalopathy event in 50% vs. 50%
– 2-year survival 81% vs. 88%
– 5-year survival 62% vs. 61%
⚬ TIPS associated with substantially higher rates of thrombosis, stenosis, and reintervention
⚬ Reference - Gastroenterology 2006 May;130(6):1643 , commentary can be found in
Gastroenterology 2006 Sep;131(3):978
Guidelines and Resources
Guidelines
International guidelines
● Baveno VI consensus workshop recommendations on stratifying risk and individualizing care for
portal hypertension can be found in J Hepatol 2015 Sep;63(3):743 full-text , editorial can be found
in J Hepatol 2015 Sep;63(3):543
● World Gastroenterology Organization (WGO) practice guideline on esophageal varices can be found at
WGO 2014 Jan PDF
United States guidelines
● American College of Radiology Appropriateness Criteria for radiologic management of gastric varices
can be found in ACR 2019 PDF
● American College of Radiology/Society of Interventional Radiology/Society for Pediatric Radiology

(ACR/SIR/SPR) practice parameter for creation of transjugular intrahepatic portosystemic shunt (TIPS)
can be found at ACR/SIR/SPR 2017 PDF
● American Association for the Study of Liver Diseases (AASLD) practice guidance on portal hypertensive
bleeding in cirrhosis can be found in Hepatology 2017 Jan;65(1):310 , correction can be found in
Hepatology 2017 Jul;66(1):304, commentary can be found in Hepatology 2017 Jul;66(1):301
● American Association for the Study of Liver Diseases (AASLD) practice guideline on role of transjugular
portosystemic shunt (TIPS) in management of portal hypertension can be found in Hepatology 2010
Jan;51(1):306 , commentary can be found in Hepatology 2010 Jun;51(6):2236
● American Society for Gastrointestinal Endoscopy (ASGE) guideline on modi cations in endoscopic
practice for elderly can be found in Gastrointest Endosc 2013 Jul;78(1):1 , correction can be found in
Gastrointest Endosc 2013 Sep;78(3):559
● American Society for Gastrointestinal Endoscopy (ASGE) guideline on role of endoscopy in

management of variceal hemorrhage can be found in Gastrointest Endosc 2014 Aug;80(2):221 ,
commentary can be found in Gastrointest Endosc 2015 Mar;81(3):774
● Department of Veterans A airs Hepatitis Resource Center Program/National Hepatitis C Program

recommendations on management and treatment of patients with cirrhosis and portal hypertension
can be found in Am J Gastroenterol 2009 Jul;104(7):1802 , correction can be found in Am J
Gastroenterol 2009 Jul;104(7):1894, commentary can be found in Am J Gastroenterol 2010
Feb;105(2):470
United Kingdom guidelines
● British Society of Gastroenterology (BSG) guidelines on prevention and management of variceal

hemorrhage in patients with cirrhosis can be found in Gut 2015 Nov;64(11):1680 full-text
● National Institute for Health and Clinical Excellence (NICE)
⚬ NICE guidance on stent insertion for bleeding esophageal varices can be found at NICE 2011 Apr
27:IPG392 PDF
⚬ NICE guidance on antimicrobial stewardship: systems and processes for e ective antimicrobial
medicine use can be found at NICE 2015 Aug 18:NG15 PDF
⚬ NICE guideline on management of acute upper gastrointestinal bleeding in patients aged > 16
years can be found at NICE 2016 Aug:CG141 PDF
European guidelines
● Czech expert quality improvement guideline on transjugular intrahepatic portosystemic shunt (TIPS)
can be found in Cardiovasc Intervent Radiol 2012 Dec;35(6):1295 full-text
● Austrian consensus guideline on management and treatment of portal hypertension (Billroth III) can
be found in Wien Klin Wochenschr. 2017 Nov;129(Suppl 3):135-158 full-text
Asian guidelines
● Asian Paci c Association for Study of the Liver (APASL) recommendations on diagnosis and
management of acute variceal bleeding can be found in Hepatol Int 2011 Jun;5(2):607 full-text
Mexican guidelines
● Mexican consensus on portal hypertension can be found in Rev Gastroenterol Mex 2013 Apr-
Jun;78(2):92 full-text [Spanish]
Central and South American guidelines
● Peruvian Social Security (EsSalud) clinical practice guideline on evaluation and management of upper
gastrointestinal bleeding can be found in Rev Gastroenterol Peru 2018 Jan;38(1):89 [Spanish]
● Catalan Society of Gastroenterology and Hepatology expert position paper on evaluation and
treatment of critically ill cirrhotic patients can be found in Gastroenterol Hepatol 2016 Nov;39(9):607
[Spanish]
● Brazilian Society of Hepatology (SBH) updated 2017 recommendations on variceal bleeding can be
found in Arq Gastroenterol 2017 Dec;54(4):349 full-text
Review articles
● review of prevention and treatment of variceal hemorrhage can be found in Liver Int 2017 Jan;37
Suppl 1:104
● review of management of gastrointestinal varices can be found in World J Gastrointest Pharmacol

Ther 2019 Jan 21;10(1):1
● review of new developments in management of acute variceal hemorrhage can be found in

Gastroenterology 2018 May;154(7):1964
● review of endoscopic management of esophageal varices can be found in World J Gastrointest Endosc
2012 Jul 16;4(7):312 full-text
● review of endoscopic treatments for portal hypertension-related bleeding can be found in

Gastrointest Endosc Clin N Am 2019 Apr;29(2):321 and Hepatol Int 2018 Feb;12(Suppl 1):91
● review of endovascular management of variceal hemorrhage can be found in Semin Intervent Radiol
2018 Aug;35(3):169
● review of medical therapy for variceal bleeding can be found in Gastrointest Endosc Clin N Am 2015
Jul;25(3):479
● review of endoscopic diagnosis and therapy for variceal bleeding can be found in Gastrointest Endosc
Clin N Am 2015 Jul;25(3):491
● review of blood and volume resuscitation for variceal hemorrhage can be found in Ann Am Thorac Soc
2015 Jul;12(7):1100
● review of management of varices and variceal hemorrhage in cirrhosis can be found in N Engl J Med
2010 Mar 4;362(9):823 , correction can be found in N Engl J Med 2011 Feb 3;364(5):490,
commentary can be found in N Engl J Med 2010 Jun 17;362(24):2331
● review of management of variceal and nonvariceal upper gastrointestinal bleeding in patients with
cirrhosis can be found in Therap Adv Gastroenterol 2014 Sep;7(5):206 full-text
● review of varices and variceal hemorrhage in cirrhosis can be found in Clin Gastroenterol Hepatol
2015 Nov;13(12):2109
● review of management of gastric varices can be found in World J Hepatol 2019 Mar 27;11(3):250
● review of management of acute esophageal variceal bleeding in patients with cirrhosis can be found
in Curr Med Res Opin 2016;32(3):467
● review of TIPS stent selection for management of portal hypertension in cirrhosis can be found in
World J Gastroenterol 2014 Jun 7;20(21):6470
● review of pharmacologic treatment and prophylactic strategies for variceal bleeding can be found in
Drugs 2008;68(16):2303
Patient Information
● handout on gastrointestinal bleeding from EBSCO Health Library or in Spanish
● handout on management of variceal bleeding from Canadian Liver Foundation
● handout on portal hypertension from British Liver Trust
● information on managing the intensive care unit experience from American Thoracic Society PDF
References
General references used
1. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk
strati cation, diagnosis, and management: 2016 practice guidance by the American Association for
the study of liver diseases. Hepatology. 2017 Jan;65(1):310-35 , correction can be found in
Hepatology 2017 Jul;66(1):304 , commentary can be found in Hepatology 2017 Sep;66(3):1009
2. Cremers I, Ribeiro S. Management of variceal and nonvariceal upper gastrointestinal bleeding in

patients with cirrhosis. Therap Adv Gastroenterol. 2014 Sep;7(5):206-16 full-text
3. de Franchis R; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno
VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol.
2015 Sep;63(3):743-52 full-text , editorial can be found in J Hepatol 2015 Sep;63(3):543 ,
commentary can be found in J Hepatol 2015 Oct;63(4):1048
Recommendation grading systems used
● American Association for the Study of Liver Diseases (AASLD) quality of evidence ratings
⚬ Grade I - randomized controlled trials

⚬ Grade II-1 - controlled trials without randomization
⚬ Grade II-2 - cohort or case-control analytic studies
⚬ Grade II-3 - multiple time series, dramatic uncontrolled experiments
⚬ Grade III - opinions of respected authorities, descriptive epidemiology
⚬ Reference - AASLD guideline on role of transjugular portosystemic shunt (TIPS) in management of
portal hypertension (Hepatology 2010 Jan;51(1):306 PDF ), commentary can be found in
Hepatology 2010 Jun;51(6):2236
● Baveno VI consensus workshop uses Oxford Centre for Evidence Based Medicine (CEBM) 2009
grading system for evidence and recommendations
⚬ grades of recommendation
– Grade A - consistent level 1 studies

– Grade B - consistent level 2 or 3 studies or extrapolations from level 1 studies
– Grade C - level 4 studies or extrapolations from level 2 or 3 studies
– Grade D - level 5 evidence or troublingly inconsistent or inconclusive studies of any level
⚬ levels of evidence
– Level 1a - systematic review with homogeneity of randomized controlled trials (RCTs)

– Level 1b - individual RCT with narrow con dence interval
– Level 1c - all or none case series
– Level 2a - systematic review with homogeneity of cohort studies
– Level 2b - individual cohort study or low-quality RCT
– Level 2c - "outcomes" research or ecological studies
– Level 3a - systematic review with homogeneity of case-control studies
– Level 3b - individual case-control study
– Level 4 - case series, poor-quality cohort or case-control studies
– Level 5 - expert opinion without explicit critical appraisal; or based on physiology, bench
research, or " rst principles"
⚬ Reference - Baveno VI consensus workshop recommendations on stratifying risk and
individualizing care for portal hypertension (J Hepatol 2015 Sep;63(3):743 full text ), editorial
can be found in J Hepatol 2015 Sep;63(3):543 , commentary can be found in Ann Hepatol 2016
Mar-Apr;15(2):289
Synthesized Recommendation Grading System for DynaMed Content

● The DynaMed Team systematically monitors clinical evidence to continuously provide a synthesis of
the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based
Methodology ).
● Guideline recommendations summarized in the body of a DynaMed topic are provided with the
recommendation grading system used in the original guideline(s), and allow users to quickly see
where guidelines agree and where guidelines di er from each other and from the current evidence.
● In DynaMed content, we synthesize the current evidence, current guidelines from leading authorities,
and clinical expertise to provide recommendations to support clinical decision-making in the Overview
& Recommendations section.
● We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to

classify synthesized recommendations as Strong or Weak.
⚬ Strong recommendations are used when, based on the available evidence, clinicians (without
con icts of interest) consistently have a high degree of con dence that the desirable consequences
(health bene ts, decreased costs and burdens) outweigh the undesirable consequences (harms,
costs, burdens).
⚬ Weak recommendations are used when, based on the available evidence, clinicians believe that
desirable and undesirable consequences are nely balanced, or appreciable uncertainty exists
about the magnitude of expected consequences (bene ts and harms). Weak recommendations are
used when clinicians disagree in judgments of relative bene t and harm, or have limited
con dence in their judgments. Weak recommendations are also used when the range of patient
values and preferences suggests that informed patients are likely to make di erent choices.
● DynaMed synthesized recommendations (in the Overview & Recommendations section) are
determined with a systematic methodology:
⚬ Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological
expertise and ≥ 1 with content domain expertise) aware of the best current evidence for bene ts
and harms, and the recommendations from guidelines.
⚬ Recommendations are phrased to match the strength of recommendation. Strong
recommendations use "should do" phrasing, or phrasing implying an expectation to perform the
recommended action for most patients. Weak recommendations use "consider" or "suggested"
phrasing.
⚬ Recommendations are explicitly labeled as Strong recommendations or Weak
recommendations when a quali ed group has explicitly deliberated on making such a
recommendation. Group deliberation may occur during guideline development. When group
deliberation occurs through DynaMed Team-initiated groups:
– Clinical questions will be formulated using the PICO (Population, Intervention, Comparison,
Outcome) framework for all outcomes of interest speci c to the recommendation to be
developed.
– Systematic searches will be conducted for any clinical questions where systematic searches
were not already completed through DynaMed content development.
– Evidence will be summarized for recommendation panel review including for each outcome, the
relative importance of the outcome, the estimated e ects comparing intervention and
comparison, the sample size, and the overall quality rating for the body of evidence.
– Recommendation panel members will be selected to include at least 3 members that together
have su cient clinical expertise for the subject(s) pertinent to the recommendation,
methodological expertise for the evidence being considered, and experience with guideline
development.
– All recommendation panel members must disclose any potential con icts of interest
(professional, intellectual, and nancial), and will not be included for the speci c panel if a
signi cant con ict exists for the recommendation in question.
– Panel members will make Strong recommendations if and only if there is consistent
agreement in a high con dence in the likelihood that desirable consequences outweigh
undesirable consequences across the majority of expected patient values and preferences.
Panel members will make Weak recommendations if there is limited con dence (or
inconsistent assessment or dissenting opinions) that desirable consequences outweigh
undesirable consequences across the majority of expected patient values and preferences. No
recommendation will be made if there is insu cient con dence to make a recommendation.
– All steps in this process (including evidence summaries which were shared with the panel, and
identi cation of panel members) will be transparent and accessible in support of the
recommendation.
⚬ Recommendations are veri ed by ≥ 1 editor with methodological expertise, not involved in
recommendation drafting or development, with explicit con rmation that Strong
recommendations are adequately supported.
⚬ Recommendations are published only after consensus is established with agreement in phrasing
and strength of recommendation by all editors.
⚬ If consensus cannot be reached then the recommendation can be published with a notation of
"dissenting commentary" and the dissenting commentary is included in the topic details.
⚬ If recommendations are questioned during peer review or post publication by a quali ed
individual, or reevaluation is warranted based on new information detected through systematic
literature surveillance, the recommendation is subject to additional internal review.
DynaMed Editorial Process
● DynaMed topics are created and maintained by the DynaMed Editorial Team and Process .
● All editorial team members and reviewers have declared that they have no nancial or other
competing interests related to this topic, unless otherwise indicated.
● DynaMed content includes Practice-Changing Updates, with support from our partners, McMaster
University and F1000.
Special acknowledgements
● DynaMed topics are written and edited through the collaborative e orts of the above individuals.
Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice.
Recommendations Editors are actively involved in development and/or evaluation of guidelines.
● Editorial Team role de nitions
Topic Editors de ne the scope and focus of each topic by formulating a set of clinical
questions and suggesting important guidelines, clinical trials, and other data to be
addressed within each topic. Topic Editors also serve as consultants for the internal
DynaMed Editorial Team during the writing and editing process, and review the nal
topic drafts prior to publication.
Section Editors have similar responsibilities to Topic Editors but have a broader role
that includes the review of multiple topics, oversight of Topic Editors, and systematic
surveillance of the medical literature.
Recommendations Editors provide explicit review of Overview and

Recommendations sections to ensure that all recommendations are sound,
supported, and evidence-based. This process is described in "Synthesized
Recommendation Grading."
Deputy Editors oversee DynaMed internal publishing groups. Each is responsible for
all content published within that group, including supervising topic development at
all stages of the writing and editing process, nal review of all topics prior to
publication, and direction of an internal team.
How to cite
National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):
● DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T550160, Acute
Variceal Hemorrhage - Treatment; [updated 2018 Nov 30, cited place cited date here]. Available from
https://www.dynamed.com/topics/dmp~AN~T550160. Registration and login required.
Published by EBSCO Information Services. Copyright © 2020, EBSCO Information Services. All rights reserved. No part of
this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying,
recording, or by any information storage and retrieval system, without permission.
EBSCO Information Services accepts no liability for advice or information given herein or errors/omissions in the text. It is
merely intended as a general informational overview of the subject for the healthcare professional.

Acute Variceal Hemorrhage - Treatment

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Acute Variceal Hemorrhage - Treatment

Uploaded by

Copyright:

Available Formats

Acute Variceal Hemorrhage - Treatment

Overview and Recommendations

Evaluation and management

● Perform esophagogastroduodenoscopy (EGD) within 12 hours to diagnose and treat variceal

● Transjugular intrahepatic portosystemic shunt (TIPS) is indicated if esophageal variceal bleeding

● In patients who bleed from gastric fundal varices:

● Acute Variceal Hemorrhage

● Esophageal Variceal Hemorrhage - Primary Prophylaxis

● Esophageal Variceal Hemorrhage - Prevention of Rebleeding

Recommendations from Professional Organizations

● Baveno VI 2015 international workshop consensus recommendations on treatment of acute variceal

– goal of resuscitation is to preserve tissue perfusion; volume restitution should be given to

⚬ insu cient evidence for recommendation about management of coagulopathy and

● patients with advanced cirrhosis (Baveno Level 1b, Grade A)

– associated with high incidence of severe adverse events

American Association for the Study of Liver Diseases (AASLD)

acute variceal hemorrhage 1

Drug Recommended Dose Duration of Therapy

Octreotide 50 mcg IV bolus 2-5 days

Vasopressin – Continuous IV 24 hours

Somatostatin 250 mcg IV bolus 2-5 days

Terlipressin – Initial dose for 48 2-5 days

⚬ perform esophagogastroduodenoscopy (EGD) within 12 hours of admission (in hemodynamically

⚬ in patients without early TIPS

– continue IV vasoactive therapy for 2 -5 days

– Child-Pugh-Turcotte Classi cation for Severity of Liver Disease

National Institute for Health and Care Excellence (NICE)

● NICE 2016 guidance for managing complications in patients with cirrhosis

⚬ in patients with upper gastrointestinal bleeding and cirrhosis, o er prophylactic antibiotics IV

● admit to intensive care 1 , 2

● assess for cirrhosis via 2

● assess and protect airway as needed 1 , 2

⚬ no strong data supporting prophylactic endotracheal intubation

– goal of resuscitation is to preserve tissue perfusion; volume restitution should be given to

complications, and increased survival 2

● management of coagulopathy and thrombocytopenia

⚬ insu cient evidence for recommendation about management of coagulopathy and

continued bleeding or rebleeding 2

Level 1b, Grade A) 3

● additional support may include

⚬ renal support by maintaining urine output > 50 mL/hour

– monitor blood glucose

⚬ monitoring mental state and avoiding sedation

reduced portal pressure and variceal bleeding 1 , 2

⚬ ideally during transport or on admission

● additional recommendations for vasoactive drugs

diagnosis, and management of portal hypertension and acute variceal hemorrhage 1

Drug Recommended Dose Duration of Therapy

Octreotide 50 mcg IV bolus 2-5 days

Vasopressin ● Continuous IV 24 hours

Somatostatin 250 mcg IV bolus 2-5 days

Terlipressin ● Initial dose for 48 2-5 days

⚬ Baveno VI international workshop consensus recommendations 3

– vasoactive drugs options include octreotide, somatostatin, terlipressin, and vapreotide

SYSTEMATIC REVIEW: Aliment Pharmacol Ther 2012 Jun;35(11):1267 | Full Text

⚬ no signi cant di erence in hemostasis comparing control to

⚬ Reference - Aliment Pharmacol Ther 2012 Jun;35(11):1267 full-text

● clinical use limited by multiple side e ects including

⚬ cardiac and peripheral ischemia

⚬ continuous vasopressin IV 0.2-0.4 units/minute (maximum 0.8 units/minute) for 24 hours

– initial dose 40 mcg/minute (maximum 400 mcg/minute)

RANDOMIZED TRIAL: Hepatology 1986 May-Jun;6(3):410

– hemorrhage controlled in 68% vs. 44% of episodes (p < 0.05, NNT 5)

⚬ Reference - Hepatology 1986 May-Jun;6(3):410