Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding (UGIB) is a significant and potentially life-threatening worldwide problem. Despite advances in diagnosis and treatment, mortality and morbidity have remained constant.¹ Bleeding from the upper gastrointestinal tract (GIT) is about 4 times as common as bleeding from the lower GIT. Typically patients present with bleeding from a peptic ulcer and about 80% of such ulcers stop bleeding. Increasing age and co-morbidity increase mortality. It is important to identify patients with a low probability of re-bleeding from patients with a high probability of re-bleeding.

A cause is found in 80% of cases. Approximate percentages given.
Note the predominance of peptic ulcer disease:

• Peptic ulcer disease 35 to 50%:
  • Duodenal ulcer 25%
  • Gastric ulcer 20%
• Gastroduodenal erosions 8 to 15%
• Oesophagitis 5 to 15%
• Oesophageal varices 5 to 10%
• 'Mallory-Weiss' tears 15%
• Upper gastrointestinal malignancy 1%
• Vascular malformations 5%
• Rare causes - less than 5%:
  • Dieulafoy's lesion (a vascular malformation of the proximal stomach)
  • Angiodysplasia
  • Haemobilia (bleeding from the gallbladder or biliary tree)
  • Pancreatic pseudocyst and pseudo-aneurysm
  • Aortoenteric fistula
  • Bleeding diathesis
  • Ehlers-Danlos syndrome
  • Pseudoxanthoma elasticum
  • Gastric antral vascular ectasia
  • Rendu-Osler-Weber syndrome

• The strong association of Helicobacter pylori (H. pylori) infection with duodenal ulcer is worthy of special mention. The organism disrupts the mucosal barrier and causes inflammation in the gastric and duodenal mucosae. Eradication reduces the risk of both recurrent ulcers and recurrent haemorrhage.
• Non-steroidal anti-inflammatory drugs (NSAIDS) are the second most important aetiological factor. They exert an effect on cyclooxygenase-1 leading to impaired resistance of the mucosa to acid.
• The size of the bleeding vessel is important in prognosis. Visible vessels are usually between 0.3 mm and 1.8 mm. Large bleeding vessels cause faster blood loss. Generally larger vessels are found deeper in the submucosa and serosa and more specifically high in the lesser curve of the stomach and postero-inferiorly in the duodenal bulb.

The incidence of UGIB is between 47 and 116 per 100,000 population.¹ There are about 2,500 admissions to hospital every year in the United Kingdom for UGIB. Incidence is highest in areas of low socioeconomic status.

Risk factors for upper gastrointestinal bleeding

An aging population with associated conditions and a worse prognosis has helped maintain constant mortality figures despite advances in treatment. Mortality is about 7% in patients admitted because of bleeding but some three times higher amongst those developing UGIB whilst in hospital.² Peptic ulcer disease is the most common cause of UGIB. Risk factors for peptic ulcer disease are:

• Alcohol abuse
• Chronic renal failure
• Non-steroidal anti-inflammatory use
• Age
• Low socio-economic class

Although duodenal ulcers are more common than gastric ulcers, both contribute nearly equally to the incidence of UGIB. After an initial bleed the risk factors for re-bleeding, with associated higher mortality, are:

• Age over 60
• Presence of signs of shock at admission
• Coagulopathy
• Pulsatile haemorrhage
• Cardiovascular disease

History

• Is there abdominal pain?
• History of other gastrointestinal symptoms should be sought. The symptoms in order of frequency are:
  • Haematemesis including coffee-ground emesis: 40 to 50%
  • Melaena: 70 to 80%
  • Haematochezia (red or maroon stool): 15 to 20%
  • Syncope: 14%
  • Presyncope: 43%
  • Dyspepsia:18%
  • Epigastric pain: 41%
  • Diffuse abdominal pain:10%
  • Weight loss: 12%
  • Jaundice: 5%
• Alcohol intake.
• Past history of bleeding (haematemesis or melaena) or of anaemia.
• Drug history is important. Drugs such as NSAIDs, aspirin and corticosteroids are an important cause of bleeding. Iron and bismuth may mimic melaena.
• Retching may precede bleeding with a 'Mallory-Weiss' tear.

Examination

The main aim of examination is to assess blood loss and look for signs of shock. A secondary aim is to look for signs of underlying disease and significant co-morbid conditions. For example:

• Pallor and signs of anaemia should be sought
• Pulse and blood pressure
• Postural hypotension may be detected and usually indicates a blood loss of 20% or more
• Other signs of shock:
  • Cool extremities
  • Chest pain
  • Confusion
  • Delirium
• Evidence of dehydration (dry mucosa, sunken eyes, skin turgor reduced)
• Stigmata of liver disease may be present (jaundice, gynaecomastia, ascites, spider naevi, flap etc)
• Signs of a tumour may be present (nodular liver, abdominal mass, lymphadenopathy)
• Subcutaneous emphysema and vomiting suggests Boerhaave's syndrome (oesophageal perforation)
• Urine output should be monitored (oliguria is a sign of shock)

Other conditions which may form part of the differential diagnosis include:

• Abdominal aortic aneurysm
• Boerhaave's syndrome
• Cholecystitis
• Coeliac sprue
• Dengue fever
• Disseminated intravascular coagulation
• Zollinger-Ellison syndrome
• Von Willebrand's disease

Laboratory tests

• Full blood count
• Crossmatch blood (usually between 2 and 6 units according to rate of active bleeding)
• Coagulation profile:
  • Platelet count
  • Prothrombin time with activated partial thromboplastin time and an international normalised ratio (INR)
  • Fibrinogen level
• Liver function tests to detect underlying liver disease
• Plasma fibrinogen level
• Urea and electrolytes
• BUN-to-creatinine ratio (greater than 36 in renal insufficiency suggests UGIB)
• Calcium level should be assessed to detect hyperparathyroid patients and to monitor the effect of citrated blood transfusions
• Gastrin levels can identify the rare gastrinomas causing UGIB

Note:

• Haemoglobin is measured serially (4-6 hourly in the first day) to help assess trend. The requirement for transfusion is based on initial haemoglobin and a clinical assessment of shock. Co-morbid conditions such as advanced cardiovascular disease require transfusion to help prevent myocardial ischaemia.
• A consumptive coagulopathy may occur with UGIB. This may be associated with thrombocytopenia. A platelet count of less than 50 with active bleeding requires platelet transfusion and fresh frozen plasma to try to make up for depleted clotting factors.
• Coagulopathy may be a marker also for advanced liver disease. Low fibrinogen and abnormal liver function tests may also indicate liver disease.

Imaging

• CXR:
  • May identify aspiration pneumonia
  • Pleural effusion
  • Perforated oesophagus
• Erect and supine abdominal X ray to exclude perforated viscus and ileus
• CT scan and ultrasound can identify:
  • Liver disease
  • Cholecystitis with haemorrhage
  • Pancreatitis with haemorrhage and pseudocyst
  • Aortoenteric fistulae
• Nuclear medicine scans have been used to identify areas of active haemorrhage
• Angiography may be useful if endoscopy fails to identify site of bleeding

Assessment of bleeding severity and re-bleeding

Bleeding severity can be assessed by:³

• The extent of blood loss
• The degree of shock

However there are other factors which affect risk of death:

• Age: deaths under age 40 years are rare. 30% of patients over 90 years old with UGIB die as a result of the bleed.
• Co-morbidity: complications are more likely with co-morbid disease.
• Shock: the presence of signs of shock confers a worse prognosis.
• Endoscopic findings: much work has been done on classifying and identifying endoscopic findings which correlate with high risk. For example:
  • 'Mallory-Weiss' tears or clean ulcers have a low risk of re-bleeding and death.
  • Active bleeding in a shocked patient carries an 80% risk of re-bleeding or death.
  • Non-bleeding but visible vessel has a 50% risk of re-bleeding.

Various methods have been designed to assess the risk of re-bleeding. These include Rockall score (see below) and Baylor score. Use of these remains controversial.

Rockall Numerical Risk Scoring System³

Resuscitation is a priority

It has been demonstrated that early and aggressive resuscitation reduces mortality in UGIB.⁴

• Maintain airway - remember vomitus can lead to airway obstruction.
• Provide high flow oxygen - this will aid tissue perfusion.
• Correct fluid losses (place 2 wide bore cannulae and also send bloods at the same time). Initial fluid resuscitation may be with crystalloids or colloids; give intravenous blood when 30% of circulating volume is lost.² Major haemorrhage protocols should be in place.²

Once patient is more stable

• Assess the patient, taking history and examining the patient as above - a collateral history might be needed.
• Identify and treat any co-morbid conditions.
• Estimate the severity of bleeding (as above).

Rockall score - initial assessment or at admission

Calculate the initial Rockall score:

• If 0, then consider patient for discharge or non-admission with out-patient follow-up.
• Rockall score >0 - i.e. all other patients - should be considered for admission and early endoscopy and should have a full Rockall score calculation.

Patients who have a Rockall score >0 should have an early endoscopy which will allow calculation of their full Rockall score.²

Endoscopy²

• Ideally, endoscopy should be performed within 24 hours.
• Endoscopy can be used both in diagnosis and therapy.
• Therapy might involve injection of adrenaline or other sclerosants, thermal coagulation or application of clips.
• Meta-analysis of trials has shown that endoscopic haemostatic techniques reduce bleeding, reduce the need for surgery and reduce mortality.⁵
• Endoscopic therapy should be applied to the following:
  • Actively bleeding lesion
  • Non-bleeding visible vessels
  • Ulcers with adherent clot
• The preference is for dual therapy, e.g. injection of adrenaline with thermal coagulation.
• High dose PPI should be given to those with major peptic ulcer bleeding, i.e. active bleeding or non-bleeding visible vessel.
• All other patients who do not receive endoscopic therapy should commence oral PPI post-procedure.

Post-initial endoscopy²

Calculate the full (post-endoscopic) Rockall score:

• Score <3 is associated with low risk of re-bleeding or death and can be considered for early discharge.
• Full Rockall score >3 indicates patients need further close observation as an inpatient.
• Careful monitoring is needed after endoscopy for UGIB (pulse, blood pressure, urine output). It is imperative to identify re-bleeding or continuing bleeding.
• Repeat endoscopy (within 24 hours) is needed if the initial endoscopy was sub-optimal, e.g. poor visualisation or in patients in whom re-bleeding is likely to be life-threatening.
• Occasionally major re-bleeding may be an indication for surgical intervention without further endoscopy.
• If patients are stable 4-6 hours after endoscopy they should be put on a light diet, as there is no benefit in continued fasting.

• Routine bloods
• Observation on the general ward
• Elective endoscopy
• Early discharge from hospital

• This is associated with high mortality and need for urgent intervention.
• Subsequent therapies may require:
  • Further endoscopic treatment
  • Surgery
  • Angiography with selective arterial embolisation

Surgical intervention

Surgical intervention is required when endoscopic techniques fail or are contra-indicated. Clinical judgement is required and consideration given to local expertise.

• In general it is recommended:
  • To inform surgeons early of the possibility of surgery
  • To use the most experienced personnel available
  • To avoid operations in the middle of the night
• The particular procedure required depends on a number of factors, not least the site of bleeding. Gastric ulcers are probably best excised. There are few studies comparing the different techniques.

Medical management post-endoscopy²

H. pylori eradication - see Helicobacter Pylori article:

• All patients with bleeding peptic ulcer should be tested for H. pylori, e.g. urea breath test and biopsy specimen.
• Patients who test positive should receive a 1-week course of eradication therapy.
• This should be followed by 3 further weeks with ulcer healing treatment.
• All therapy can be discontinued after successful healing of peptic ulcers provided patients are not taking NSAIDs.
• A negative urea breath test should be confirmed on the initial biopsy specimen taken prior to diagnosis and before any PPI therapy was given.
• Two weeks after successful therapy and stopping of all medication, a repeat urea breath test should be performed to confirm successful eradication.
• Unsuccessful eradication should be treated with second-line therapy.

Other points to note

• PPI use is not recommended prior to diagnosis by endoscopy in the latest SIGN guidance, however current hospital protocols often include PPI use for suspected UGIB before endoscopic confirmation.
• There is insufficient evidence to use somatostatin or tranexamic acid in UGIB.
• In selected patients (e.g. variceal haemorrhage) it may be appropriate to use terlipressin or octreotide and, in the case of uncontrolled UGIB in an unstable patient, balloon tamponade may be necessary, e.g. Sengstaken-Blakemore, Minnesota or Linton-Nachlas tubes.
• Patients with an UGIB might need to be admitted to a high-dependency unit or intensive care unit. This decision should be clinical and used in conjunction with the Rockall score.
• Some hospitals have beds specifically for patients with an UGIB. Evidence suggests that patients with UGIB should be assessed and managed in dedicated units as their outcome is improved.²
• Emergency endoscopy should be available 24 hours a day in such units.
• Note that patients with liver disease are a special case and have separate guidelines for management.

Continuing other medication²

• Anticoagulants and antiplatelet agents should be stopped during the acute phase and restarted later only if there is a clear indication.
• Patients who have healed ulcers and were H. pylori negative and require aspirin or NSAIDs or COX2 inhibitors, should be given concomitant PPI.
• SSRIs should be used in caution in patients at risk of UGIB or who have had a previous UGIB (especially if other drugs such as aspirin or NSAIDs are used).
• Corticosteroids will also need to be used carefully and probably with concomitant PPI in high-risk patients or those on high doses.

The complications of UGIB are self-evident. Other complications can arise from treatments administered. For example:

• Endoscopy:
  • Aspiration pneumonia
  • Perforation
  • Complications from coagulation, laser treatments
• Surgery:
  • Ileus
  • Sepsis
  • Wound problems
• Salvage surgery for patients who continue to bleed is associated with a high mortality

Mortality is about 7% in patients admitted with an UGIB. It is as high as 26% in patients who develop bleeding whilst in hospital having been admitted for another cause.² A score of less than 3 using the Rockall system above is associated with an excellent prognosis, whereas a score of 8 or above is associated with high mortality.³

Prognosis is worse with the following:²

• Increasing age
• Co-morbidity
• Liver disease
• Shock at presentation
• Inpatient
• Continued bleeding after presentation
• Haematemesis
• Haematochezia
• Elevated blood urea

Mortality is reported to be lower in specialist units, possibly because of adherence to protocols rather than because of technical advances. The prognosis in liver disease relates significantly to the severity of the liver disease rather than to the magnitude of the haemorrhage.

The most important factor to consider is treatment for H. pylori infection. This should be completed as an outpatient.

1. Fallah MA, Prakash C, Edmundowicz S; Acute gastrointestinal bleeding. Med Clin North Am. 2000 Sep;84(5):1183-208. [abstract]
2. Management of acute upper and lower gastrointestinal bleeding, SIGN Clinical Guideline (September 2008)
3. Rockall TA, Logan RF, Devlin HB, et al; Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996 Mar;38(3):316-21. [abstract]
4. Baradarian R, Ramdhaney S, Chapalamadugu R, et al; Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality. Am J Gastroenterol. 2004 Apr;99(4):619-22. [abstract]
5. Cook DJ, Guyatt GH, Salena BJ, et al; Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Gastroenterology. 1992 Jan;102(1):139-48. [abstract]