Management of acute upper GI bleeding

Question 1

Key points

Answer 1

• Initial priorities are resuscitation, risk assessment,
  and early endoscopic treatment as described in
  National Institute for Health and Care Excellence
  Guidance 141
• Non-variceal re-bleeds require interventional
  radiological embolization, or surgery. Repeat
  oesophagogastroduodenoscopy may allow decisions to be made at this point

Variceal bleeds not responding to endoscopic
therapy need management in a specialist centre,
benefit from balloon tamponade if unstable and
should be considered for transjugular intrahepatic
portosystemic shunt.

• Upper gastrointestinal bleeding due to stress
  ulceration in the ICU will occur in up to 15% of
  patients not on prophylactic treatment. Current
  National Institute for Health and Care Excellence
  guidance recommends either H2-receptor antagonists or proton pump inhibitors for primary
  prophylaxis

Question 2

Incidence

Answer 2

acute upper gastrointestinal bleeding (UGIB) in the United Kingdom
varies over the range 84–172/ 100 000 year

Mortality due to upper GI bleeding was found
to be 7% among new admissions, rising to 30% in those who
bled as inpatients

Question 3

PC

Answer 3

UGIB refers to bleeding from any point proximal to the duodenojejunal flexure. It presents clinically with haematemesis
and/or melaena. Fresh bleeding per rectum is usually indicative
of lower GI bleeding, however massive UGIB can present with
passing of red blood clots rectally

90% of cases, melaena
results from any upper GI bleeding

Question 4

CAuses

Answer 4

In developing countries with endemic viral hepatitis, variceal bleeding is the commonest category. In Western communities, peptic ulcer disease (PUD) is the commonest cause

e UK, the commonest causes of UGIB are PUD,
oesophagogastric varices with or without portal hypertensive gastropathy
and oesophagitis

Ulcerative Portal hypertension Tumours

Question 5

Initial assessment

Answer 5

assessment of
severity, general supportive measures and identification of the
cause, should occur in parallel with direct, specific therapies

It is imperative to clarify if the patient has previously presented with UGIB. Sixty per cent of patients who re-bleed, do so from the same source

Drug history is equally important. For example, nonsteroidal anti-inflammatory drugs (NSAIDS) may be identified as a precipitant for bleeding.
Anticoagulant therapies such as
warfarin and new oral anticoagulants (NOACs; direct inhibitors
of thrombin or activated factor Xa) increase the likelihood of
severe bleeding and require specific treatment.

Co-morbid illness may point to a cause for bleeding, such as
chronic liver disease and variceal bleeding. It also identifies
patients at higher risk of developing complications, so requiring

Question 6

Initial assessment exam

Answer 6

Further establish a potential cause for bleeding and determine severity, so aiding appropriate triage of patients. Signs of chronic liver disease such as
jaundice and spider naevi point to variceal bleeding. Significant
upper abdominal tenderness and rigidity may suggest a complication such as perforation

determines the changes in vital signs,
with some caveats. Initial signs of mild blood loss would
include resting tachycardia. Fifteen per cent loss of blood volume is associated with postural hypotension indicated by a
drop in systolic blood pressure greater than 20 mm Hg or with
an increase in heart rate greater than 20 beats mi

Question 7

Initial laboratory tests

Answer 7

should include full blood count, liver
enzymes, bilirubin, serum albumin, urea and electrolytes, coagulation screen, and samples for cross matching of blood. Other
specific tests may be required as appropriate, such as screening
for viral hepatitis.

Question 8

General supportive measures

Answer 8

Patients may require supplemental oxygen to increase oxygen
delivery, particularly with co-morbid lung or heart disease.

Early elective tracheal intubation should be considered in those
with ongoing haematemesis and altered mental or respiratory
status to minimize the risk of aspiration, whilst aiding endoscopy.

Significant co-morbidities lead to a much higher risk of
complications. For those patients and others with signs of
refractory shock
lactate > 4 mmol litre1
, pH < 7.3 after
resuscitation

Invasive arterial monitoring allows closer monitoring of haemodynamic status and facilitates frequent blood
gas and laboratory samples to be taken. Central venous line
insertion, provided coagulation is not deranged, gives secure i.v.
access and allows central venous pressure measurements to be
taken. Flow guided methods of monitoring such as LidCO or
oesophageal pressure monitoring give a more accurate guide to
volume status.

Question 9

Circulation support

Answer 9

In all patients, two wide-bore cannulas (16G at least) should
be established. Patients should not be given anything by mouth.
Fluid resuscitation starts with rapid infusion of isotonic crystalloid solution, such as Hartmann’s. In patients non-responsive
to crystalloids, resuscitation is continued using blood and fresh
frozen plasma (FFPs). In many centres, a major haemorrhage
protocol can be activated. In extreme circumstances, O negative
blood may be required initially. The authors do not advocate
the use of colloids in resuscitation, given concerns over kidney
injury, worsened coagulopathy, risk of anaphylaxis, and a lack
of benefit over crystalloids.

Question 10

Blood transfusion

Answer 10

should usually be targeted at patients with haemoglobin (Hb)
level below 70 g litre3 . 4 Evidence comes from a randomized
controlled trial which compared mortality rates at 45 days
between patients randomised to either a restrictive transfusion
strategy (if Hb <70 g litre1 ) or liberal transfusion strategy (if Hb
<90 g litre

The
TRIGGER (Transfusion in Gastrointestinal Bleeding strictive strategies are generally preferred with the exception of patients with
ischaemic heart disease and possibly those with ongoing
haemorrhage

The NICE CG 141 also recommends giving FFP to bleeding
patients with a prothrombin time (or INR) or activated partial
thromboplastin time greater than 1.5 times normal, which are
generally accepted times in other scenarios with major haemorrhage

Cryoprecipitate should be given for fibrinogen levels
below 1.5 g litre1 despite FFP administration. Platelet transfusion should be given to patients with platelet count <50 109
litre1 and considered in those actively bleeding while established on anti-platelet therapy such as clopidogrel. Patients
actively bleeding while taking warfarin therapy should receive
Prothrombin complex concentrate (PCC)

Question 11

Bleeding and anticoagulants

Answer 11

In bleeding, the activation of a major haemorrhage protocol
and early involvement of senior clinicians, including haematologists is vital.

This is particularly important for those taking NOAC drugs,
the effects of which are not easily reversed.

The European Heart Rhythm Association produced practical guidance on their use.

Recommendations include the use of PCC
alongside general resuscitation in life threatening bleeding.

Dabigatran is the only NOAC drug which may be fully
reversed using an antidote. Idarucizumab has been shown in a
pilot trial to achieve haemostasis in serious bleeding from
dabigatran.7 This monoclonal antibody drug is currently pending approval for use in the UK.

Question 12

Pharmacotherapy

Answer 12

1. PPI
2. Terlipressin

Question 13

PPI

Answer 13

Proton pump inhibitors (PPIs) increase gastric pH to above 6.0.
This optimizes platelet function, inhibits fibrinolysis and
reduces peptic activity, so increasing clot stabilization over
bleeding ulcers. PPI use prior to endoscopy in UGIB was evaluated in a Cochrane systematic review of RCTs comparing PPI
vs control [placebo, or H2-receptor antagonists (H2RAs) or no
treatment].8 It found that PPI significantly reduced the need for
endoscopic therapy and reduced the stigmata of recent haemorrhage during index endoscopy, but there was no evidence
of improved clinically important outcomes, namely mortality,
re-bleeding or need for surgery. NICE therefore advises against
the use of PPI prior to endoscopy.3 PPIs should be prescribed
postendoscopy for those with non-variceal UGIB and stigmata
of recent haemorrhage

Question 14

Terlipressin

Answer 14

Terlipressin is a synthetic analogue of Vasopressin, with a
slow, sustained release allowing administration via intermittent injections. It reduces portal blood flow, hence variceal bleeding. It is the only vasoactive drug proven to reduce
mortality

uring resuscitation measures and prior to endoscopic confirmation. Terlipressin can be stopped once definitive
haemostasis is achieved and in any case after 5 days.

Question 15

octreotide

Answer 15

In a recent RCT, somatostatin and its
metabolite octreotide have proven to be as effective as
terlipressin.10 In 2015 the British Society of Gastroenterology
(BSG) published guidance on managing variceal haemorrhage.11
This suggests using terlipressin or somatostatin and if unavailable using octreotide off license

Question 16

erythromycin

Answer 16

I.V. erythromycin as a prokinetic administered prior to
endoscopy vs no erythromycin was evaluated in a systematic
review of seven RCTs.12 Erythromycin was associated with a
greater chance of adequate visualization of the gastric mucosa,
less need for second endoscopy, less blood transfusion and
shorter hospital stay. Due to limitations in the studies (e.g. gastric visualization definitions varied across the studies), an
update to NICE CG 141, did not recommend erythromycin use
as standard.

Question 17

Tranexamic acid

Abx

Answer 17

is not currently recommended by NICE for
acute UGIB. The BSG document recommends further study to
look for benefit in variceal bleeding.

Antibiotics with gram negative cover, such as third generation cephalosporins Cefotaxime, improve mortality rates and reduce bacterial infections. Cochrane meta-analysis13 also shows fewer
early re-bleeds.

Antibiotic choice is dictated by local resistance
patterns and availability.

Question 18

Risk stratification

Answer 18

The Rockall and Blatchford scores are well-validated risk stratification systems used in UGIB

Used appropriately, these scores help identify patients likely
to require Critical Care support, ensure timely interventions
and help identify those suitable for early discharge from hospital. NICE advises the use of GBS at first assessment and full RS
postendoscopy

Question 19

Rockall score

Answer 19

Table 2
Score 0 1 2 3

1. Age (yr)
   <60 60–79 80 N/A
2. Pulse <100 >100 >100 N/A
3. Systolic blood pressure >100 >100 <100 N/A
4. Comorbidities None Nil major Ischaemic heart disease, cardiac failure,
   other major co-morbidity
   Renal or liver failure,
   disseminated malignancy
5. Diagnosis Mallory–Weiss or
   no lesion/pathology
   All other diagnosis Malignant lesion N/A
6. Stigmata of haemorrhage on endoscopy
   None, or dark spot only None, or dark
   spot only
   Blood, adherent clot, visible/spurting
   vessel
   N/A

Question 20

Endoscopic therapies

Answer 20

high risk lesions, meaning
active bleeding, visible non-bleeding vessels and adherent clots.
They include injection therapies, mechanical therapies, and
thermal interventions

Adrenaline (1:10 000 or 1:20 000) is injected in increments of
0.5–1.5 ml aliquots to the four quadrants around high-risk stigmata. It is easy to administer and can produce a clear field
around a bleeding vessel

Question 21

After endoscopy

Answer 21

Acid suppression using a PPI should be used after endoscopic
haemostasis. An updated large Cochrane meta-analysis showed
that compared with H2 blocker or placebo, PPI reduced re-bleeding, surgical intervention and need for repeated endoscopic
treatment. Use of PPI reduced mortality in those with active
bleeding or non-bleeding vessels

stration in terms of clinical outcomes, remains controversial. However, high dose IV PPI seems the most costeffective.19 Current international consensus guidelines recommend high-dose i.v. PPI therapy e.g. Pantoprazole 80 mg bolus
followed by 8 mg h1 for 3 days.15
Helicobacter pylori eradication should be offered to all who test
positive for the infection. Eradication therapy was shown to be
superior to PPI alone in preventing re-bleeding. Those with PUD, but
negative for H. pylori at the time of acute UGIB, should be retested

Question 22

Specific therapy in variceal UGIB

Answer 22

The techniques involved are either endoscopic variceal ligation (EVL) or
endoscopic sclerotherapy (ES). Initial success rates of 90% are
reported. EVL was found to be as effective as ES in achieving hemostasis, but in meta-analysis EVL was found superior in rates
of re-bleeding, strictures and mortality.1

Balloon tamponade is effective at achieving haemostasis in
acute variceal bleeding, but has high rates of re-bleeding and complications. Balloons should be used temporarily when endoscopic
therapy has failed and until either further endoscopic treatment,
transjugular intrahepatic portosystemic shunt (TIPSS) or surgery
is performed.

e use of the Sengstaken–
Blakemore tube but alternatives include a Minnesota tube. Balloon
insertion is preferably preceded by tracheal intubation to avoid
aspiration. Endoscopic insertion over a guide wire has been suggested to reduce the risk of oesophageal rupture. The gastric balloon is inflated up to a volume of 500 ml with air, with the
oesophageal balloon inflated up to 45 mm Hg for ongoing bleeding.
Balloons are usually left in situ for 24–48 h, with deflation regularly
to assess for re-bleedin

Question 23

TIPSS

Answer 23

TIPSS should be considered when variceal bleeding is not
controlled via endoscopic therapy alone. This involves radiologically establishing a porto-caval shunt, using the transjugular
intrahepatic route

uccess rate at stopping bleeding is
quoted as 90–100%, especially in oesophageal varices. With gastric varices, development of spontaneous splenorenal collaterals may cause re-bleeding. With refractory bleeding and no
other therapeutic options, salvage TIPSS may be considered

Question 24

TIPS

Answer 24

Transjugular intrahepatic portosystemic shunt (TIPS)

acute liver failure, hepatic encephalopathy, hemorrhage, biliary injury, injury to surrounding organs, TIPS thrombosis, TIPS dysfunction, and TIPS migration