Christos Triantos

University Hospital of Patras, Greece

Complications of portal hypertension: what’s new?

Management of variceal bleeding

I have reveived fees for serving as a speaker for Bristol-Myers Squibb and Gilead.

General principles of management

Management of haemostasis

Uncontrolled variceal bleeding

Patients at high risk of early rebleeding

Management of gastric variceal bleeding

Management of variceal bleeding

46-86 %

cirrhotics varices Non-variceal

patients 336 114

5 day failure 14.6% P=0.03 7%

Rebleed ≤ 5d 4.8% 1.8%

Deaths ≤ 5d 9.2% P=0.18 5.3%

Rebleed ≤ 6w 19% P=0.019 9.6%

Deaths ≤ 6 w 20.8% P=0.16 14.9%

PROSPECTIVE STUDY OF UPPER GI BLEEDING IN CIRRHOTICS

(D’Amico 2003)

CP C and large, actively spurting varices - less likely to achieve spontaneous

hemostasis

Prandi DAm J Surg 1976

The greatest risk - 48 to 72 hours, > 50 % - 10 days de Franchis R, Gastroenterol Clin North Am 1992

The 1-year rate of recurrent bleeding - 60% Bosch J,. Lancet 2003

Recurrent variceal bleeding

Although Graham et al 42% mortality (6 w) in 1981, now 20%

6-week mortality, 15 to 20%, 0% Child class A - 30% Child class C disease

The risk of bleeding and of death in patients who survive six weeks is similar to

patients who have never bled

Villanueva C,. J Hepatol 2006

Abraldes JG, J Hepatol 2008

Bosch J, Hepatology 2008

D’ Amico G, Hepatology 2003

Graham DY, Gastroenterology 1981

De Franchis R, Gastroenterol Clin North Am 1992

Mortality

Bleeding related mortality

1475 pts

28 studies

control arms

26% CP-C

Incident risk ratios for cirrhosis

complications or interventions,

each year from 2002 to

2010.Derived from interaction

terms (e.g. HRS x 2002, x

2003,…x 2010; Sepsis x 2002, x

2003, …2010; etc.) in Poisson

model for inpatient mortality.

Incident risk ratios for cirrhosis complications or interventions,

each year from 2002 to 2010. Monica Schmidt, Gastroenterology 2015

20 mmHG < 20 mmHGHVPG at admission

HVPG and Variceal bleeding (Moitinho, Gastroenterology 1999)

MELD score was comparable to ICU prognostic models in predicting mortality.

hemodynamic resuscitation

prevention and treatment of complications

treatment of bleeding

GENERAL PRINCIPLES OF MANAGEMENT

level of evidence from 1 = highest to 5 = lowest

grade of recommendation from A = strongest to D = weakest

Baveno V

The time frame for the acute bleeding episode should be 120 h

(5 days)

Failure is defined as death or need to change therapy defined by one of

the following criteria: (2b;B)

Fresh hematemesis or NG aspiration of ≥ 100 ml of fresh

blood ≥ 2 h after the start of a specific drug treatment or therapeutic

endoscopy

Development of hypovolaemic shock

3 g drop in Hb (9% drop of Ht) within any 24 h period (no transfusion)

Definitions

The goal of resuscitation is to preserve tissue

perfusion

A (Airway)

B (Breathing)

C (Circulation)

Variceal bleeding

Preferably the access to the

circulation should be both

peripheral and central

Blood volume restitution following a bleeding worsens

the portal hypertension syndrome in cirrhotic rats with a high

portal-systemic shunt index

As compared with a liberal transfusion strategy, a restrictive strategy

significantly improved outcomes in patients with acute

upper gastrointestinal bleeding

Endotracheal intubation in patients with massive bleedingRudolph SJ, Gastrointest Endosc 2003

One study suggested that it may increase the risk Koch DG, Dig Dis Sci 2007

Facilitates the performance of endoscopy and endoscopic therapy

Intubation of the patient before endoscopy should be strongly considered

because of the high risk of aspiration of blood

ASGE 2014

A nasogastric tube can help decompress the stomach and assist in clearing it

Aspiration

2 RCTs and a meta-analysis no benefit

Bosch J, Gastroenterology 2004

Bosch J, Hepatology 2008

Martí-Carvajal AJ, Cochrane Database Syst Rev 2012

A second meta-analysis - beneficial in patients with active bleeding

Bendtsen F,. J Hepatol 2014

Further clarification !

Recombinant factor VIIa

MARGARET S. SOZIO

NAGA CHALASANI

PRBC transfusion should be done conservatively at a target

hemoglobin level between 7 and 8 g/dl, although transfusion

policy in individual patients should also consider other factors

such as co-morbidities, age, hemodynamic status and ongoing

bleeding (1b;A).

Recommendations regarding management of coagulopathy and

thrombocytopenia cannot be made on the basis of currently available data (5;D).

In patients with significant coagulopathy or thrombocytopenia, transfusion of fresh

frozen plasma and/or platelets should be consideredASGE 2014

Bacterial infection and failure to control bleeding

Goulis, J Hepatology 1998

20 %

The most common sites are

urinary tract infections (12 - 29 %)

spontaneous bacterial peritonitis (7 -23 %)

respiratory infections (6 - 10 %)

primary bacteremia (4 - 11 %)

8 trials, 864 patients. A significant beneficial effect on decreasing mortality

(RR 0.73, 95% CI 0.55 to 0.95) and the incidence of bacterial infections (RR

0.40, 95% CI 0.32 to 0.51) was observed.

Soares-Weiser K, Cochrane Database Syst Rev 2002; CD002907

Infection and use of prophylactic antibiotics

No difference in

hospital mortality

Child–Pugh class A had lower rates of bacterial infection and lower mortality

rates in the absence of antibiotic prophylaxis than patients categorized

as classes B or C.

The recommendation for routine antibiotic prophylaxis for this subgroup

requires further evaluation

Baveno V

Antibiotic prophylaxis

from admission (1a;A).

Patients with GI bleeding and features

suggesting cirrhosis should have upper

endoscopy as soon as possible after

admission(within 12 h) (5;D).

Baveno V

Prevention of hepatic encephalopathy

Recommendations regarding management and prevention of

encephalopathy in patients with cirrhosis and upper GI

bleeding cannot be made on the basis of currently available

data (5;D).

Lactulose is effective in prevention of HE in patients with cirrhosis and acute

variceal bleeding

J Gastroenterol Hepatol. 2011 Jun;26(6):996-1003.

Prophylaxis of hepatic encephalopathy in acute variceal bleed: a randomized

controlled trial of lactulose versus no lactulose.

Sharma P, Agrawal A, Sharma BC, Sarin SK.

Rifaximin was not superior to lactulose for prophylaxis

Gut. 2014 Oct 15. pii: gutjnl-2014-308521.

Randomised controlled trial of lactulose versus rifaximin for prophylaxis of

hepatic encephalopathy in patients with acute variceal bleed.

Maharshi S, Sharma BC, Srivastava S, Jindal A.

Hepatic encephalopathy

The risk of renal failure can be minimized by appropriate volume

replacement and avoidance of aminoglycosides

Alcoholic subjects should receive thiamine and be monitored for

withdrawal symptoms.

Nutritionally depleted subjects may develop hypophosphatemia and

hypokalemia, especially after dextrose infusions which raise serum

insulin concentrations; insulin drives both phosphate and potassium

into the cellsKnochel JP. Hypophosphatemia in the alcoholic. Arch Intern Med 1980

Protein synthesis is severely diminished following a simulated upper

GI bleed in patients with cirrhosisOlde Damink SW. J Hepatol 2008

Other measures

Management of haemostasis

In all patients who have varices or who are at

risk for having varices

Should not be delayed pending confirmation that

the source of bleeding is indeed from varices

Pharmacologic therapy

The use of vasoactive agents was associated with a significantly lower risk

of acute all-cause mortality and transfusion requirements, and improved

control of bleeding and shorter hospital stay.

Interpretation, Early administration of natural somatostatin

continued for 120 h, combined with additional bolus

injections, is more effective than placebo in the overall

control of acute variceal haemorrhage in patients with

cirrhosis undergoing sclerotherapy

control of bleeding

mortality

Christos Triantos,,John Goulis,

Andrew K Burroughs.

Portal hypertensive bleeding 2011

sclerotherapy (S) vs

sclerotherapy combined with vasoactive agents

The use of variceal ligation instead of sclerotherapy as emergency endoscopic therapy

added to somatostatin for the treatment of acute variceal bleeding

significantly improves the efficacy and safety

Pharmacological treatment

- In suspected variceal bleeding, vasoactive drugs should be started as soon as possible,

before endoscopy (1b;A).

- Vasoactive drugs (terlipressin, somatostatin, octreotide, vapreotide) should be used in

combination with endoscopic therapy and continued for up to 5 days (1a;A).

Endoscopic treatment

- Endoscopic therapy is recommended in any patient who presents with documented

upper GI bleeding and in whom esophageal varices are the cause of bleeding (1a;A).

- Ligation (EVL) is the recommended form of endoscopic therapy for acute esophageal

variceal bleeding, although sclerotherapy may be used in the acute setting if ligation is

technically difficult (1b;A)

Management of variceal bleeding

‘ The definition of uncontrolled variceal bleeding includes:

continued/early variceal rebleeding (within 5

days) despite 2 sessions of therapeutic endoscopy,

continued variceal bleeding despite balloon tamponade

continued/early gastric or ectopic variceal bleeding despite

vasoconstrictor therapy ’

O’Brien J, Triantos C, Burroughs A, Nat Rev Gastroenterol Hepatol. 2013

Uncontrolled variceal bleeding

A. AVGERINOS & A. ARMONIS, Scand J Gastroenterol 1994

Balloon tamponade

Balloon tamponade should be reserved for those patients

with variceal haemorrhage in whom bleeding

continues despite conservative treatment, or as the

first form of treatment only if sclerotherapy is not available

‘Balloon tamponade should only be

used in massive bleeding as a

temporary ‘‘bridge” until definitive

treatment can be instituted

(for a maximum of 24 h, preferably

in an intensive care facility)’

Balloon tamponade – Baveno V

Self-expanding

metal stents

Maufa F. International Journal of Hepatology 2012

Initial control of bleeding 87.5%, mean duration 10 (±6) min, mortality 25.0%, Zakaria MS, Saudi j Gastroenterol 2013

VL failure, Successful initial hemostasis 5/5 . Holster, Endoscopy 2013

M. Vangeli, D. Patch, A.K. Burroughs, J Hepatol. 2002

Uncontrolled variceal bleeding- TIPS

75-100 % 6-27 % 15-75 %

Persistent bleeding despite combined pharmacological and

endoscopic therapy is best managed by TIPS with PTFE-covered

stents (2b;B).

Re-bleeding during the first 5 days may be managed by a second

attempt at endoscopic therapy. If re-bleeding is severe,

PTFE-covered TIPS is likely the best option (2b;B).

Management of treatment failures - Baveno V

Patients at high risk of early rebleeding

In patients at high risk for treatment failure, the early use of TIPS

was associated with significant reductions in treatment failure and in mortality

‘ An early TIPS within 72 h (ideally ≤24 h) should

be considered in patients at high-risk of treatment

failure (e.g. Child-Pugh class C <14 points or

Child class B with active bleeding) after initial

pharmacological and endoscopic therapy’

Early TIPS placement – Baveno V

Management of gastric variceal bleeding

5-33% in patients with portal hypertension

bleeding 25%/y

Gastric varices

Balloon-Occluded Retrograde Transvenous Obliteration (BRTO)

Park J, Dig Dis Sci 2014

Hemoglobin level between 7 and 8 g/dl

Antibiotics from admission

Pharmacologic therapy should not be delayed

Balloon tamponade as a ‘‘bridge”

Persistent bleeding or re-bleeding consider TIPS

IGV/GOV2- N-butyl-cyanoacrylate , TIPS

GOV1 - N-butyl-cyanoacrylate, band ligation

Take home messages

The manegement of uncontrolled variceal

bleeding includes

1. Balloon tamponade

2. Self-expanding metal stents

3. TIPS

4. All the above

Which of the following is correct

1. The time frame for the acute bleeding episode should be 6 months

2. Pharmacologic therapy should not be delayed pending confirmation

that the source of bleeding is indeed from varices

3. Vasoactive drugs should not be used in combination with

endoscopic therapy

4. Sclerotherapy is the recommended form of endoscopic therapy for

acute esophageal variceal bleeding