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 is about 4 times as common as lower gastrointestinal tract bleeding. Typically patients present with bleeding from a peptic ulcer and about 80% of such ulcers stop bleeding. Increasing age and comorbidity increase mortality. It is important to identify patients with a low probability of rebleeding from patients with a high probability of rebleeding.

• The strong association of Helicobacter 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.
• Nonsteroidal anti-inflammatory drugs (NSAIDS) are the second most important aetiological factor. The 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 posteroinferiorly in the duodenal bulb.

The incidence of upper gastrointestinal bleeding is between 47 and 116 per 100,000 population.^1,2 There are about 2500 admissions to hospital every year in the United Kingdom for upper gastrointestinal haemorrhage. Incidence is highest in areas of low socioeconomic status.²

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 11% 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 inflammatory use
• Age
• Low socioeconomic 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 rebleeding, 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 non-steroidal anti-inflammatories 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 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 syndrome
• Cholecystitis
• Coeliac sprue
• Dengue fever
• Disseminated intravascular coagulation
• Zollinger-Ellison syndrome
• Von Willebrand 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 and 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

Endoscopy

This is useful for:

• Diagnosing the cause of bleeding
• Estimating prognosis
• Therapeutic haemostasis (see under management below)

Patients with minor bleeding can be managed with observation on the general ward followed by elective endoscopy and probably an early hospital discharge.² Major bleeding requires active resuscitation in an HDU or ITU setting followed by endoscopy urgently. Recently it has become apparent with therapeutic endoscopy that prognosis can be improved in severe bleeding. This is most appropriately performed in dedicated endoscopy suites or operating theatres with full facilities for resuscitation.

Contraindications to upper endoscopy

These include:

• Uncooperative patient
• Acute myocardial infarction (unless haemorrhage life-threatening)
• Perforated viscus

Assessment of bleeding severity³

This can be assessed by:

• The extent of blood loss
• The degree of shock

However there are other factors which affect risk of death:²

• 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 rebleeding and death.
  • Active bleeding in a shocked patient carries an 80% risk of rebleeding or death.
  • Non bleeding but visible vessel has a 50% risk of rebleeding.

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

Co-morbid conditions have a significant effect on prognosis as embodied in the Rockall assessment above. Patients with advanced renal or liver disease and disseminated cancer fare worst.

Patients with an UGIB (other than minor bleeding²) should be admitted to a high dependency unit or intensive care unit. Some hospitals have beds specifically for patients with an UGIB. 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. It is important as when dealing with all critically ill patients that a list of tasks is completed although in practice some of these may be performed simultaneously rather than sequentially :

• Assess the patient taking history and examining the patient as above.
• Identify and treat any co-morbid conditions.
• Take blood for routine bloods as above.
• Establish venous access for intravenous fluids.
• Estimate the severity of bleeding. This can be difficult to assess without the additional information from endoscopy (see table for Rockall scoring system). Clinical judgement is needed to establish:
  • Mild to moderate bleeding:
    • Normal pulse and blood pressure
    • Haemoglobin concentration greater than 100 g/l
    • No or insignificant co-morbidity
    • Usually less than 60 years of age
  • Severe bleeding:
    • Pulse over 100 beats/minute and systolic blood pressure less than 100 mm Hg
    • Haemoglobin concentration less than 100 g/l
    • Most will have significant co-morbidity
    • Patients are usually over 60 years of age

Resuscitation

It has been demonstrated that early and aggressive resuscitation reduces mortality in UGIB.⁴ Resuscitation is a priority to:

• Correct fluid losses
• Restore blood pressure

Therapeutic endoscopy

Meta-analysis of trials⁵ has shown that endoscopic haemostatic techniques:

• Reduce rebleeding
• Reduce the need for surgery
• Reduce mortality

Choice of technique is influenced by the size of the bleeding vessel. Above 2 mm diameter vessels are likely to require clips, banding or surgery. Angiographic techniques may be required when surgery is high risk. Interventional radiology using stents is being developed as a therapeutic option.
Techniques include:

• Banding and injection sclerotherapy for varices.
• Injection of adrenaline solution achieves haemostasis in 95% of cases but 15-20% will rebleed.
• Injection of sclerosants reduces rebleeding but introduces the risk of necrosis at the injection site.
• Injection of agents to stimulate clot formation such as fibrin glue or thrombin have been shown to be effective but are not widely available.
• Application of heat:
  • Laser therapy is no longer used. It was used in combination with adrenaline but could increase bleeding by drilling into the bleeding vessel.
  • Heater probe (teflon coated). This heats to about 250 degrees centigrade and achieves haemostasis with heat and pressure. It is as effective as adrenaline.
  • Multipolar coagulation (BICAP) is as effective as the heater probe.
  • The argon plasma coagulator requires further study. It seems less effective if vessels are larger than 1 mm diameter.
  • Combinations of heat with adrenaline have been tried but are no better than adrenaline alone except in active arterial bleeding.
• Application of clips. These perform well in trials but may be difficult to apply.

Drug therapy²

Three classes of drugs have been tested for non variceal bleeding:

• Acid suppressing drugs:
  • H2- receptor antagonists have not been shown to be effective in UGIB.
  • Proton pump inhibitors (PPIs). In general small studies have shown benefit. Consensus suggests use after endoscopic therapy at high dose for all patients with bleeding ulcers (for example 80mg of omeprazole followed by 8mg per hour for 72 hours).
• Somatostatin. There is insufficient data to recommend use.
• Anti-fibrinolytic drugs. Tranexamic acid has been used but more work is needed.

Management after endoscopy

• Careful monitoring is needed after endoscopy for UGIB (pulse, blood pressure, urine output). It is imperative to identify rebleeding or continuing bleeding.
• 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.
• Repeat endoscopy is required if there is evidence of rebleeding (for example with melaena or unstable observations).
• Occasionally major rebleeding may be an indication for surgical intervention without further endoscopy.

Surgical intervention

Surgical intervention is required when endoscopic techniques fail or are contraindicated. 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.

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 11% in patients admitted with an UGIB.² It is as high as 33% in patients who develop bleeding whilst in hospital. 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 Most deaths occur in elderly patients with co-morbidity. Mortality is reported to be lower in specialist units possibly because of adherence to protocols rather than because of technical advances.² The prognosis in liver disease relates significantly to the severity of the liver disease rather than to the magnitude of the haemorrhage.²

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