Upper gastrointestinal bleeding: quick reference

Immediate orientation

Two questions govern the initial management:

1. Is the patient haemodynamically compromised, or are there signs of ongoing major bleeding?
2. Is there cirrhosis, or another strong suspicion of portal hypertension?

Variceal and ulcer bleeding are managed differently from the first minute. Peptic ulcer remains the commonest cause of upper gastrointestinal bleeding, but the differential diagnosis includes oesophagitis, gastritis, a Mallory-Weiss tear, a Dieulafoy lesion, angiodysplasia, malignancy and an aortoenteric fistula. Variceal bleeding generally has a higher early mortality than non-variceal bleeding [1,2].

Upper gastrointestinal bleeding can present as haematemesis, coffee-ground vomiting or melaena. Haematochezia can occur in massive upper bleeding with rapid intestinal transit. Coffee-ground vomiting is less specific than fresh haematemesis and can also be seen when the bleeding is slow or has stopped.

The first steps

Assess the severity of the bleeding clinically

Signs of major or ongoing bleeding are:

• hypotension or a postural drop
• tachycardia
• a cold periphery and delayed capillary refill
• confusion, drowsiness or syncope
• oliguria
• a rising lactate or metabolic acidosis
• repeated fresh haematemesis
• haematochezia in combination with circulatory compromise
• a rapidly falling haemoglobin after fluid treatment has been started
• a continuing transfusion requirement.

A normal haemoglobin early on does not exclude major bleeding. In acute blood loss, plasma and red cells are lost simultaneously, which means the haemoglobin can be normal before fluid has redistributed or been given. In massive bleeding, the decision to transfuse must therefore not be based on the haemoglobin alone [3].

The airway

Do not intubate every patient routinely before endoscopy. Observational data do not show that prophylactic intubation reduces aspiration or mortality. It has on the contrary been associated with more pneumonia and a longer stay, although the results are influenced by the fact that the sickest patients are more often intubated [4].

Intubation is reasonable in:

• a reduced level of consciousness with inadequate protective reflexes
• active major haematemesis
• severe agitation
• respiratory failure
• an anticipated difficult or prolonged endoscopic intervention
• a need for general anaesthesia for other reasons.

Extubate as soon as it is safe to do so after the endoscopy.

Fluid and monitoring

Use a balanced crystalloid in the first instance. Give small boluses, for example 250 to 500 mL, with immediate reassessment of the blood pressure, pulse, peripheral perfusion, mental state and chest findings. Avoid large, uncritical volumes of crystalloid, which cause haemodilution, hypothermia and tissue oedema. The aim is adequate organ perfusion while control of the bleeding is arranged, not the rapid normalisation of every blood pressure reading with fluid [5].

An unstable patient, ongoing major bleeding, significant comorbidity, a high rate of transfusion or a need for vasoactive drugs all argue for intensive care or an equivalent level of monitoring.

Platelets and coagulation tests

With ongoing major bleeding and a platelet count around or below 50 × 10^9/L, platelet transfusion may be considered, particularly before therapeutic endoscopy. The evidence for an exact threshold in gastrointestinal bleeding is, however, weak [1].

In cirrhosis the INR does not reliably reflect the overall bleeding risk. Do not therefore give plasma routinely merely to normalise the INR. Plasma can increase the intravascular volume and the portal pressure without reliably improving haemostasis. Discuss individual treatment in massive bleeding, marked hypofibrinogenaemia, disseminated intravascular coagulation, or a documented deficiency after massive transfusion.

Anticoagulants and antiplatelet drugs

Anticoagulants

In serious or life-threatening bleeding, anticoagulants must be paused and rapid reversal considered. Establish:

• the drug
• the indication
• the last dose
• renal and hepatic function
• any concurrent antiplatelet therapy
• previous thrombosis
• a mechanical valve or recent venous thromboembolism.

In serious warfarin-associated bleeding, intravenous vitamin K and four-factor prothrombin complex concentrate are used according to the local protocol. Prothrombin complex concentrate gives faster correction and less volume load than plasma [6].

With dabigatran, idarucizumab can be used in life-threatening bleeding where a residual drug effect is likely. With apixaban or rivaroxaban, andexanet alfa or non-specific prothrombin complex concentrate may be appropriate depending on local availability and guidelines. Reversal carries a thrombotic risk and must be directed at patients with serious bleeding and probable clinically relevant anticoagulation [6].

A normal INR or APTT does not exclude a clinically significant effect of a factor Xa inhibitor. For direct oral anticoagulants, the time since the last dose and the renal function are often more important than routine coagulation tests.

Coagulopathy must not lead to endoscopy being postponed unnecessarily. Reversal, resuscitation and the planning of endoscopy proceed in parallel [5].

Antiplatelet drugs

Aspirin given for secondary prevention, for example after myocardial infarction, stroke or coronary intervention, should be continued where possible. If aspirin has to be paused in life-threatening bleeding, it must be restarted as soon as haemostasis has been achieved, usually within 3 to 5 days [5].

Aspirin used only for primary prevention can generally be stopped after a significant gastrointestinal bleed.

With dual antiplatelet therapy, particularly after a recently inserted coronary stent, a cardiologist must be contacted urgently. If one drug has to be paused in major bleeding, aspirin should generally be retained while the P2Y12 inhibitor is paused for as short a time as possible [1].

Plan the restart during the first 24 hours

The thrombotic risk does not disappear because the patient is bleeding. Document:

• which drug has been paused
• the indication for the treatment
• the planned time or the criteria for restarting it
• the doctor or clinic responsible.

After controlled non-variceal bleeding, anticoagulation should often be restarted within, or shortly after, 7 days, but the timing is individualised. A mechanical heart valve, recent thromboembolism and a very high stroke risk may justify an earlier restart. Direct oral anticoagulants reach full effect quickly after restarting [5,6].

Transfusion

A restrictive transfusion strategy reduces the number of units transfused and has in meta-analyses of upper gastrointestinal bleeding been associated with a lower mortality and less rebleeding than a liberal strategy [7]. More recent analyses confirm that a restrictive strategy does not increase mortality or rebleeding, but the exact optimal threshold in patients with cardiac ischaemia remains uncertain [8]. In the broader transfusion literature, restrictive thresholds reduce transfusion exposure without a definite increase in 30-day mortality, but the evidence is less robust in acute myocardial infarction and certain cardiovascular conditions [9].

In variceal bleeding, over-transfusion is particularly inappropriate, since an increased intravascular volume can raise the portal pressure and promote continued or recurrent bleeding.

Normally give one unit of red cells at a time to a stable patient, and check the clinical response and the haemoglobin before transfusing further. This does not apply in massive ongoing bleeding.

Risk assessment

The Glasgow-Blatchford score

The Glasgow-Blatchford score, GBS, is calculated before endoscopy and includes:

• urea
• haemoglobin
• systolic blood pressure
• pulse
• melaena
• syncope
• liver disease
• heart failure.

A GBS of 0 to 1 identifies patients at very low risk of needing transfusion, endoscopic treatment, surgery or of dying. These patients can often be managed as outpatients with planned endoscopy, provided they are well, have reliable follow-up and can return promptly if they deteriorate [5,10].

A meta-analysis of 38 studies with more than 36,000 patients found that a GBS of at most 1 gave the best identification of low-risk patients. A threshold of 2 can identify more patients for outpatient management, but it is not as well established in guidelines and should not be used without a local procedure [10].

Limitations

The GBS is better at identifying low risk than at determining exactly which high-risk patient needs immediate endoscopy. AIMS65 and the pre-endoscopic Rockall score can provide prognostic information, particularly on mortality, but must not replace the GBS when the question is whether the patient can be discharged safely [11].

The GBS must not override clinical judgement. Admit the patient despite a low score in, for example:

• ongoing haematemesis
• increasing melaena
• suspected variceal bleeding
• anticoagulation-related bleeding that requires reversal
• significant comorbidity
• a social or geographical situation that makes a prompt return difficult
• an uncertain diagnosis.

Time to endoscopy

Resuscitate before endoscopy. An unstable patient is not made safer by being moved immediately to endoscopy without the airway, the circulation, the blood products and the anaesthetic cover being in place.

For non-variceal bleeding, endoscopy within 24 hours improves the chances of diagnosis, treatment and early discharge. Very early endoscopy, for example within 6 hours, has by contrast not been shown to give better mortality or less rebleeding than endoscopy later during the first 24 hours in resuscitated patients [5,12].

In suspected variceal bleeding, endoscopy within 12 hours is recommended, but only after vasoactive treatment, antibiotics and resuscitation have been started [13].

Drugs before endoscopy

Proton pump inhibitors before endoscopy

A proton pump inhibitor before endoscopy probably reduces the need for endoscopic haemostasis, but it has not been shown to reduce mortality, rebleeding or the need for surgery. The treatment is therefore reasonable in suspected non-variceal bleeding, particularly if the endoscopy is delayed, but it must not be given with such priority that the endoscopy is postponed [14].

A continuous high-dose infusion is above all a treatment after endoscopic haemostasis of a high-risk ulcer. Before endoscopy, an intravenous bolus or repeated doses can be given according to the local protocol.

Vasoactive treatment in suspected variceal bleeding

Start vasoactive treatment as soon as variceal bleeding is suspected — that is, before endoscopy. Terlipressin, somatostatin and octreotide reduce splanchnic blood flow and the portal pressure. Continue the treatment for 2 to 5 days after variceal bleeding has been confirmed, depending on the control of bleeding and on local practice [13].

Be alert to contraindications and adverse effects. Terlipressin can cause, among other things, ischaemic complications, hyponatraemia and respiratory complications. The choice of agent and the dose follow the local protocol.

Antibiotics in cirrhosis

As a general rule, all patients with cirrhosis and upper gastrointestinal bleeding must be given antibiotic prophylaxis early, whether the final source of bleeding is varices or, for example, an ulcer. Ceftriaxone 1 g intravenously once daily for up to 7 days is an internationally recommended option, but local resistance, allergy, renal function and previous culture results must guide the choice of agent [13].

Older randomised trials showed reduced infection, rebleeding and mortality with antibiotic prophylaxis [15]. A later meta-analysis including both randomised and observational studies also found lower mortality, infection and rebleeding [16]. A more recent analysis has, however, questioned how large the mortality benefit is in modern practice and pointed to the low to moderate quality of the studies. The risk of infection is reduced more clearly than the mortality, and the optimal duration of treatment is not firmly established [17]. Until better data are available, international guidelines and local procedures should be followed.

Erythromycin

Intravenous erythromycin before endoscopy can improve the view by emptying the stomach of blood and clots. Consider it particularly in major haematemesis, ongoing bleeding, or a suspicion of a great deal of blood in the stomach. A common guideline dose is 250 mg intravenously 30 to 120 minutes before endoscopy [13].

A Cochrane review found improved visualisation but an uncertain effect on mortality and rebleeding [18]. A network meta-analysis also found a reduced need for repeat endoscopy compared with placebo [19].

Take account of QT prolongation, interactions and macrolide allergy. A nasogastric tube and gastric lavage must not be used routinely for diagnostic purposes alone.

Tranexamic acid

Tranexamic acid is not recommended routinely in gastrointestinal bleeding. The large HALT-IT trial showed no reduction in bleeding-related death but an increase in venous thromboembolism with the high-dose regimen studied [1]. A later meta-analysis pooling several different bleeding populations could not entirely exclude a benefit from early tranexamic acid, but this does not change the recommendation for gastrointestinal bleeding [20].

Endoscopic treatment

Ulcer bleeding according to Forrest

In active ulcer bleeding, adrenaline injection must not be used as the sole treatment. Adrenaline can slow the bleeding and improve the view, but it must be combined with mechanical or thermal haemostasis. Clips, contact thermal treatment and other established methods are chosen according to the site of the lesion, the vessel and local expertise [5].

Where bleeding persists despite standard methods, an over-the-scope clip or a haemostatic powder can be used. Powder is often a bridge, since the risk of rebleeding can be substantial.

Oesophageal varices

Acute oesophageal variceal bleeding is treated with endoscopic band ligation in combination with vasoactive treatment already started. Ligation gives better initial control of bleeding than sclerotherapy and has largely replaced it [21].

Gastric varices

Gastric varices must not automatically be treated as oesophageal varices. The treatment depends on the anatomy:

• GOV1 can in some cases be treated with ligation or tissue adhesive.
• Fundal varices, above all GOV2 and IGV1, are usually treated with cyanoacrylate or another locally established method of obliteration.
• If treatment fails, TIPS or balloon-occluded retrograde transvenous obliteration is considered where the method is available [13].

After endoscopy

Proton pump inhibitors after endoscopic haemostasis

After successful haemostasis of a high-risk ulcer, a high-dose proton pump inhibitor is given for 72 hours. An established regimen is 80 mg intravenously as a bolus followed by 8 mg per hour as a continuous infusion. High-dose treatment with repeated intravenous boluses, or high-dose oral treatment twice daily, are acceptable alternatives according to current guidelines [5].

After the first 72 hours, a high-risk ulcer is generally treated with a proton pump inhibitor twice daily up to and including day 14, and thereafter once daily for a duration that depends on the cause and site of the ulcer and on any continuing need for an NSAID or antithrombotic treatment [3].

Helicobacter pylori

Test every patient with ulcer bleeding. Biopsy-based tests can be falsely negative during acute bleeding and concurrent proton pump inhibitor treatment. A negative test in the acute phase therefore does not exclude infection. Combined testing strategies have a higher sensitivity than single tests in this situation [22].

In practice:

1. Take a biopsy for a rapid urease test or histology at the index endoscopy if this is feasible.
2. Eradicate if the result is positive.
3. Repeat the test if the acute result is negative, generally with a urea breath test or a stool antigen test once it is possible to interrupt the proton pump inhibitor.
4. Confirm eradication after treatment has been completed.

Serology cannot distinguish current from previous infection and is therefore unsuitable for checking after treatment.

Nutrition and mobilisation

Once haemostasis has been achieved and no immediate further intervention is planned, oral nutrition can be resumed early. Patients with a low-risk ulcer rarely need to fast after the endoscopy. Mobilisation, thromboprophylaxis and the restarting of regular medication are assessed individually.

Variceal bleeding after initial haemostasis

Assess the risk and consider early TIPS

After confirmed variceal bleeding, the Child-Pugh and MELD scores must be calculated. The following patients are at high risk of treatment failure and should be discussed early for pre-emptive TIPS:

• Child-Pugh C with at most 13 points
• Child-Pugh B above 7 points with active bleeding at endoscopy despite vasoactive treatment
• in some cases a documented very high portal pressure.

Pre-emptive TIPS must be performed within 72 hours and preferably within 24 hours when the criteria are met [13]. Meta-analyses show reduced treatment failure, rebleeding and six-week mortality in selected high-risk patients [23]. Patient selection is decisive, since TIPS can precipitate encephalopathy and cardiac strain, and marked liver failure can make the procedure futile [24].

Secondary prophylaxis

After oesophageal variceal bleeding, a combination is required of:

• a non-selective beta blocker, usually propranolol or carvedilol, once the patient is haemodynamically stable
• repeated band ligation at intervals of about 1 to 4 weeks until the varices have been eradicated [13].

Do not start beta blockade during ongoing shock, marked hypotension or acute kidney injury. Acute vasoactive treatment and long-term beta blockade are two different phases of treatment.

Treatment failure and rebleeding

Non-variceal bleeding

Suspect rebleeding with:

• new haematemesis or haematochezia
• new hypotension or tachycardia
• a fall in haemoglobin after initial stabilisation
• a recurring transfusion requirement
• a rising lactate.

The first step is usually repeat endoscopy with further haemostasis. If endoscopic treatment fails, interventional radiology must be contacted for transcatheter arterial embolisation. Surgery is indicated if embolisation is unavailable, cannot be performed, or fails [5].

Compared with surgery, embolisation results in more rebleeding but fewer complications, with no definite difference in mortality. The evidence consists mainly of retrospective studies with substantial selection bias [25].

Refractory variceal bleeding

With continuing oesophageal variceal bleeding despite vasoactive treatment and endoscopic haemostasis:

1. Continue resuscitation and secure the airway.
2. Contact interventional radiology and the liver team for emergency rescue TIPS.
3. Use a self-expanding oesophageal stent or balloon tamponade as a temporary bridge to definitive treatment.

A self-expanding oesophageal stent achieved immediate control of bleeding in around 91 per cent in one meta-analysis, but rebleeding and stent migration occur. The method is a bridge, not definitive treatment [26].

Balloon tamponade can control the bleeding rapidly but carries a risk of aspiration, pressure necrosis and oesophageal rupture. It must be used by experienced staff and for the shortest possible time, generally no more than 24 hours. The plan for TIPS or other definitive treatment must be in place when the tamponade is inserted.

If the endoscopy shows no source of bleeding

With continuing or recurrent bleeding:

• consider whether the first endoscopy had a poor view
• repeat the endoscopy after erythromycin if there was a great deal of blood or clot in the stomach
• perform CT angiography during clinically significant ongoing bleeding
• proceed to angiography with the option of embolisation with a positive finding or a strong clinical suspicion
• consider a colonic source with haematochezia
• investigate the small bowel with capsule endoscopy or enteroscopy once the patient is stable and the bleeding is occult or intermittent.

In haemodynamically significant bleeding with no findings, unusual causes must be actively considered, among them an aortoenteric fistula, haemobilia, haemosuccus pancreaticus and a Dieulafoy lesion.

Red flags and pitfalls

• An aortoenteric fistula: consider this in a patient with previous aortic surgery, an aortic graft or a known aortic aneurysm. A small herald bleed can precede a catastrophic haemorrhage. A negative endoscopy does not exclude the diagnosis. Contact a vascular surgeon and perform urgent CT angiography.
• Melaena without haematemesis: this is still upper gastrointestinal bleeding until proven otherwise.
• Haematochezia with shock: this can be massive upper bleeding.
• A normal initial haemoglobin: this does not exclude a large acute blood loss.
• A raised urea in relation to the creatinine: this supports an upper source but is not diagnostic.
• Waiting for the haemoglobin before transfusing in massive bleeding: treat the clinical picture.
• Over-transfusing in variceal bleeding: aim for a haemoglobin of 70 to 90 g/L after stabilisation.
• Forgetting vasoactive treatment: give it as soon as variceal bleeding is suspected.
• Forgetting antibiotic prophylaxis in cirrhosis: give it even before the source of bleeding has been established.
• Giving plasma routinely in cirrhosis with a raised INR: the INR is a poor measure of overall haemostasis in cirrhosis.
• Using adrenaline as the sole endoscopic treatment of an ulcer: combine it with a clip or a thermal method.
• Intubating everyone routinely: intubation must have a clear clinical indication.
• Giving tranexamic acid routinely: it has no demonstrated net benefit in gastrointestinal bleeding.
• Stopping aspirin given as secondary prevention without a plan: this can increase the risk of myocardial infarction, stent thrombosis and stroke.
• Not planning the restart of anticoagulation: document the timing, the criteria and who is responsible.
• Missing hepatic encephalopathy: gastrointestinal bleeding is a common precipitant. Treat the precipitating bleed, infection, constipation, renal failure and electrolyte disturbance at the same time.
• Calling all gastric varices oesophageal varices: fundal varices often require tissue adhesive or radiological treatment, not ligation alone.
• Delaying the discussion about TIPS: high-risk patients must be identified immediately after the endoscopy, since the therapeutic window is short.

A short on-call algorithm

1. ABCDE, two large-bore cannulae, cross-match, lactate and early contact with the endoscopist.
2. Assess the circulation and activate the major haemorrhage protocol if needed.
3. Transfuse restrictively once the patient is stable, generally at a haemoglobin below 70 g/L.
4. Calculate the Glasgow-Blatchford score. A GBS of 0 to 1 can often be managed as an outpatient.
5. Suspected variceal bleeding: a vasoactive drug and antibiotics immediately.
6. Suspected non-variceal bleeding: a proton pump inhibitor can be started but must not delay the endoscopy.
7. Endoscopy within 12 hours in suspected variceal bleeding, otherwise within 24 hours after resuscitation.
8. After ulcer haemostasis: a high-dose proton pump inhibitor for 72 hours.
9. After variceal haemostasis: continue vasoactive treatment and antibiotics, and assess whether pre-emptive TIPS is needed.
10. In rebleeding: repeat endoscopy. Thereafter embolisation or surgery in non-variceal bleeding, and rescue TIPS in variceal bleeding.
11. Test every ulcer for Helicobacter pylori and repeat the test if the acute result is negative.
12. Document the restarting of anticoagulants and antiplatelet drugs.

References

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