International Consensus Recommendation for the Management of Non Variceal Bleeding Ulcers
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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