Recommendations
Key Recommendations
Admit any patient with suspected acute variceal bleeding to a high-dependency or intensive care unit.[5]
Intubate the patient before endoscopy if there is haematemesis, or there is a perceived risk of a haemodynamically unstable patient having blood in the stomach, or if the patient presents with an altered mental status (i.e., confusion).[5] Make sure the patient is appropriately resuscitated before undergoing endoscopy.
Request an urgent critical care review for any patient with ongoing haemodynamic instability despite adequate resuscitative efforts.[35]
If the patient has massive bleeding, transfuse with blood, platelets, and clotting factors in line with your local protocols.[5][39][53] Consider activating major haemorrhage protocols early.
Give terlipressin and prophylactic antibiotics (e.g., ceftriaxone) to all patients with suspected or confirmed variceal bleeding at presentation.[5][39] Be aware that terlipressin is contraindicated in patients with arterial disease, hyponatraemia, myocardial ischaemia, severe cardiac failure, or prolonged QTc interval.[37] A somatostatin analogue (e.g., octreotide) can be used as an alternative if terlipressin is contraindicated.[5]
Endoscopic band ligation is the preferred method for the treatment of upper gastrointestinal bleeding from oesophageal varices.[5][39][44]
Transjugular intrahepatic portosystemic shunt can be considered if bleeding is not controlled by band ligation.[5][39][54]
Danis stent or balloon tamponade may be considered at any time as a temporary measure if variceal bleeding has continued despite medical therapy and endoscopy is not immediately available or has failed to control bleeding, until definite treatment.[5][55]
These techniques are specialised and should only be undertaken by someone with adequate training and experience.
Acute oesophageal variceal bleeding is a medical emergency. The main treatment goals are to:
Stop the bleeding
Prevent early recurrence.
Focus management on treating varices to prevent bleeding.
Admit any patient with suspected acute variceal bleeding to a high-dependency or intensive care unit.[5]
Prioritise resuscitation in line with standard Airway, Breathing, Circulation (ABC) practice; protect the airway to prevent aspiration and obtain good peripheral venous access.[5]
Give intravenous fluids to all patients.[5][35] Follow your local protocol.
Monitor National Early Warning Score (NEWS2) and use clinical review to determine the infusion rate for your patient. Royal College of Physicians: National Early Warning Score (NEWS) 2 Opens in new window The British Society of Gastroenterology (BSG) and the National Institute for Health and Care Excellence (NICE) in the UK recommend using a crystalloid solution as a bolus of 500 mL in less than 15 minutes in haemodynamically unstable patients.[35][56] The European Society of Gastrointestinal Endoscopy guidelines recommend prompt intravascular volume replacement using crystalloid fluids in these patients.[38]
In practice, use the largest possible diameter cannula. Give intravenous fluids to maintain systolic blood pressure >90 to 100 mmHg and monitor closely. Aim to switch to blood replacement as soon as possible but beware of over-transfusion - base decisions on blood transfusion on the full clinical picture, with a restrictive approach to transfusion, aiming for a haemoglobin of 70-80 g/L in haemodynamically stable patients.[5]
Evidence from critically ill patients in general (not specifically just people with oesophageal varices) suggests that there is no difference in benefit between normal saline and a balanced crystalloid (such as Hartmann's solution [also known as Ringer's lactate] or Plasma-Lyte®), and therefore either choice of fluid is reasonable.[57][58] Check local protocols for specific recommendations on fluid choice.
Practical tip
Be aware that large volumes of normal saline as the sole fluid for resuscitation may lead to hyperchloraemic acidosis.
Also note that use of lactate-containing fluid in a patient with impaired liver metabolism may lead to a spuriously elevated lactate level, so results need to be interpreted with other markers of volume status.
Evidence: Choice of fluids
Evidence from two large randomised controlled trials (RCTs) suggests there is no difference between normal saline and a balanced crystalloid in mortality at 90 days, and therefore either option is a reasonable choice for the resuscitation of critically ill patients.
There has been extensive debate over the choice between normal saline (an unbalanced crystalloid) versus a balanced crystalloid (such as Hartmann’s solution [also known as Ringer’s lactate] or Plasma-Lyte®). Evidence from critically ill patients points to no benefits from using a balanced crystalloid in preference to normal saline. Clinical practice varies widely, so you should check local protocols.
In 2021-2022, two large double-blind RCTs were published assessing intravenous fluid resuscitation in intensive care unit (ICU) patients with a balanced crystalloid solution (Plasma-Lyte) versus normal saline: the Plasma-Lyte 148 versus Saline (PLUS) trial (53 ICUs in Australia and New Zealand; N=5037) and the Balanced Solutions in Intensive Care Study (BaSICS) trial (75 ICUs in Brazil; N=11,052).[58][57]
In the PLUS study, 45.2% of patients were admitted to ICU directly from surgery (emergency or elective), 42.3% had sepsis, and 79.0% were receiving mechanical ventilation at the time of randomisation.
In BaSICS, almost half the patients (48.4%) were admitted to ICU after elective surgery and around 68% had some form of fluid resuscitation before being randomised.
Both found no difference in 90-day mortality overall or in prespecified subgroups for patients with acute kidney injury (AKI), sepsis, or post-surgery. They also found no difference in the risk of AKI.
In BaSICS, for patients with traumatic brain injury, there was a small decrease in 90 day mortality with normal saline - however, the overall number of patients was small (<5% of total included in the study) so there is some uncertainty about this result. Patients with traumatic brain injury were excluded from PLUS as the authors felt these patients should be receiving saline or a solution of similar tonicity.
A meta-analysis of 13 RCTs (including PLUS and BaSICS) confirmed no overall difference, although the authors did highlight a non-significant trend towards a benefit of balanced solutions for risk of death.[59]
Previous evidence has been mixed.
A 2015 double-blind, cluster-randomised, double-crossover trial conducted in 4 ICUs in New Zealand (N=2278), the 0.9% Saline vs. Plasma-Lyte for ICU fluid Therapy (SPLIT) trial, found no difference for in-hospital mortality, acute kidney injury, or use of renal-replacement therapy.[60]
However, a 2018 US multicentre unblinded cluster-randomised trial - the isotonic Solutions and Major Adverse Renal events Trial (SMART), among 15,802 critically ill adults receiving ICU care - found possible small benefits from balanced crystalloid (Ringer’s lactate or Plasma-Lyte) compared with normal saline. The 30-day outcomes showed a non-significant reduced mortality in the balanced crystalloid group versus the normal saline group (10.3% vs. 11.1%; OR 0.90, 95% CI 0.80 to 1.01) and a major adverse kidney event rate of 14.3% versus 15.4% respectively (OR 0.91, 95% CI 0.84 to 0.99).[61]
A 2019 Cochrane review included 21 RCTs (N=20,213) assessing balanced crystalloids versus normal saline for resuscitation or maintenance in a critical care setting.[62]
The 3 largest RCTs in the Cochrane review (including SMART and SPLIT) all examined fluid resuscitation in adults and made up 94.2% of participants (N=19,054).
There was no difference in in‐hospital mortality (OR 0.91, 95% CI 0.83 to 1.01; high-quality evidence as assessed by GRADE), acute renal injury (OR 0.92, 95% CI 0.84 to 1.00; GRADE low), or organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; GRADE very low).
Give high-flow oxygen, if indicated.[5]
In patients with decompensated cirrhosis, manage any precipitant causes (e.g., give Pabrinex® [vitamin B substances with ascorbic acid] if the patient has a history of current excess alcohol consumption) and their complications. Follow the decompensated cirrhosis care bundle in these patients.[37]
Patients with decompensated cirrhosis have 10% to 20% in-hospital mortality. Early treatment of the complications of cirrhosis can save lives.[37]
Haemodynamically unstable patients
Intubate the patient before endoscopy if there is haematemesis, or there is a perceived risk of a haemodynamically unstable patient having blood in the stomach, or if the patient presents with an altered mental status (i.e., confusion).[5] Make sure the patient is appropriately resuscitated before undergoing endoscopy.
Practical tip
If the patient has been intubated, they will need to be managed in an intensive care or high-dependency unit until extubation.[5]
Request an urgent critical care review for any patient with ongoing haemodynamic instability despite adequate resuscitative efforts. Consider activating major haemorrhage protocols early.[35]
In patients with massive bleeding, transfuse with blood, platelets, and clotting factors in line with your local protocols.[5][39]
Practical tip
Be cautious of raising vascular pressures with excessive plasma transfusions, especially as standard coagulation tests are limited in the monitoring of patients with liver disease.[53]
Base decisions on blood transfusion on the full clinical picture; bear in mind that over-transfusion may be as damaging as under-transfusion.[39]
Give platelet transfusion to patients who are actively bleeding and have a platelet count of <50 × 109/L.[5][35][39][53] Higher thresholds may be considered in those with falling platelet counts.[53]
Give fresh frozen plasma (FFP) to patients who are actively bleeding and have a prothrombin time, (or INR) or activated partial thromboplastin time >1.5 times normal.[39][53] In ongoing major bleeding, if appropriate coagulation test results are not available, transfuse FFP in at least a 1:2 ratio with units of red blood cells (RBCs).[53]
Offer fibrinogen supplementation to patients with fibrinogen concentrations <1.5 g/L (excluding pregnant women).[53] Give cryoprecipitate to patients with a fibrinogen level that remains <1.5 g/L despite FFP use.[39]
Haemodynamically stable patients
In haemodynamically stable patients, start transfusion when the haemoglobin level falls to below 70 g/L, and maintain between 70 to 80 g/L.[5]
Do not offer platelet transfusion if the patient is haemodynamically stable and not actively bleeding.[39]
Patients taking anticoagulation therapy (e.g., warfarin, direct oral anticoagulants [DOACs])
Consider seeking advice from an appropriate specialist if the patient is taking warfarin or a DOAC.
The British Society of Gastroenterology (BSG) consensus care bundle for acute upper gastrointestinal bleeding and the 2021 update to the BSG and European Society of Gastrointestinal Endoscopy (ESGE) guideline on endoscopy in patients on antiplatelet or anticoagulant therapy recommend:[35][64]
Suspending DOACs at presentation and seeking advice from a haematologist when managing patients with severe haemorrhage to weigh up the risks and benefits of the DOAC.
Suspending warfarin at presentation.
In haemodynamically unstable patients, the 2021 update to the BSG and ESGE guideline recommends:[64]
In patients who are taking warfarin, give intravenous vitamin K and four-factor prothrombin complex concentrate. Fresh frozen plasma can be used if prothrombin complex concentrate is not available.
If the patient is taking a DOAC, consider the use of reversal agents: idarucizumab in patients taking dabigatran, and andexanet alfa in patients taking anti-factor-Xa. Intravenous four-factor prothrombin complex concentrate can be used if andexanet alfa is not available.
Note that NICE in the UK recommends:[39]
Prothrombin complex concentrate in patients who are taking warfarin and actively bleeding
Following local warfarin protocols to treat patients who are taking warfarin and whose upper gastrointestinal bleeding has stopped
Recombinant factor Vlla (eptacog alfa) when all other methods have failed.
If any medications are temporarily stopped, also seek advice on the appropriate time for these to be restarted. The 2021 update to the BSG and ESGE guideline on endoscopy in patients on antiplatelet or anticoagulant therapy recommends restarting anticoagulation:[64]
As soon as possible after 7 days of anticoagulant interruption in patients with low thrombotic risk
Preferably within 3 days of anticoagulant interruption in patients with high thrombotic risk, with heparin bridging.
Patients taking aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), or dual antiplatelet therapy
If the patient is taking aspirin, other NSAIDs (including cyclo-oxygenase-2 [COX-2] inhibitors), or dual antiplatelet therapy:
In general, continue aspirin in the acute phase, if your patient is taking this for secondary prevention:[35][39][64]
Consider seeking urgent advice from a specialist if there is major haemorrhage.
NICE doesn’t make a specific recommendation about major haemorrhage, but advises continuing aspirin only once haemostasis has been achieved.[39]
The BSG consensus care bundle for acute upper gastrointestinal bleeding and the 2021 update to the BSG and ESGE guideline on endoscopy in patients on antiplatelet or anticoagulant therapy recommend continuing aspirin if this is taken as part of dual antiplatelet therapy with a P2Y12 inhibitor (e.g., clopidogrel, prasugrel, or ticagrelor), and the P2Y12 is temporarily stopped.[35][64] However, the 2021 update to the BSG and ESGE guideline recommends that, if aspirin is stopped, it should be restarted as soon as haemostasis is achieved or there is no further evidence of haemorrhage.[64]
The BSG care bundle cites two studies that demonstrate a three-fold increase in the risk of cardiovascular or cerebrovascular events if aspirin, prescribed for the secondary prevention, is discontinued.[35][65][66]
The 2021 update to the BSG and ESGE guideline recommends considering permanently discontinuing aspirin if the patient is taking it for primary prevention:[64]
If the patient is taking any other NSAIDs (including COX-2 inhibitors), NICE recommends stopping these during the acute phase[39]
If the patient is taking dual antiplatelet therapy, seek advice from the appropriate specialist to weigh up the benefits and risks of continuing the P2Y12 inhibitor. Discuss the balance of benefits versus risk with your patient. In general, if the patient:[35]
Does not have coronary artery stents, the P2Y12 inhibitor should be stopped temporarily until haemostasis is achieved
Does have coronary artery stents, dual antiplatelet therapy should ideally be continued due to the high risk of stent thrombosis. However, the risks and benefits of doing so need to be carefully considered by a specialist.
Following risk assessment, if Glasgow-Blatchford score ≤1 consider managing the patient as an outpatient if safe and appropriate to do so. This approach is supported by latest evidence and in line with recommendations from the European Society of Gastrointestinal Endoscopy (ESGE) guidelines and a consensus care bundle for acute upper gastrointestinal (GI) bleeding led by the British Society of Gastroenterology (BSG).[35][38] Refer all patients with acute upper gastrointestinal (GI) bleeding for upper GI endoscopy.[35][38][39]
If the patient is unstable with severe acute upper GI bleeding, do this urgently, immediately after resuscitation.[35][39]
For all other patients with upper GI bleeding, do this within 24 hours of admission.[35][39]
Practical tip
Ensure that haemodynamically unstable patients are adequately resuscitated before undergoing endoscopy.
Give terlipressin to all patients with suspected variceal bleeding at presentation, unless contraindicated.[5][39] The BSG recommends a somatostatin analogue (e.g., octreotide) as an alternative to terlipressin in patients with contraindications to terlipressin.[5] Note that octreotide is used off-label for this indication in the UK.
Terlipressin is contraindicated in patients with arterial disease, hyponatraemia, myocardial ischaemia, severe cardiac failure, or prolonged QTc interval.[67]
Terlipressin is a potent vasoconstrictor; it increases systemic vascular resistance, reduces cardiac output, and reduces portal pressures by approximately 20%.[67][68]
Stop treatment with terlipressin or a somatostatin analogue after definitive haemostasis has been achieved, or after 5 days, unless there is another indication to continue.[5][39]
Give prophylactic antibiotics to all patients with suspected or confirmed variceal bleeding at presentation.[5][17][39]
Give intravenous ceftriaxone immediately.[5][29] Then, change to an antibiotic (if appropriate) recommended by your local protocols and in consultation with an infectious disease or microbiology specialist; take account of local microbial epidemiology and resistance patterns, and availability.[5]
Prophylactic antibiotics reduce the rate of bacterial infection, treatment failure, rebleeding, and mortality.[6][29][69] [
]
Refer patients to a gastroenterology service.[35] These techniques are specialised and should only be undertaken by someone with adequate training and experience.
Once the haemorrhage is confirmed by endoscopy, endoscopic band ligation is the technique of choice.[5][39][44]
The British Society of Gastroenterology recommends using balloon tamponade (via a Sengstaken Blakemore tube) temporarily if variceal bleeding has continued despite medical therapy and endoscopy is not immediately available.[5] This requires intensive care monitoring; intubation should be considered.[5] Tamponade must be removed after 24 to 36 hours.[55]
Balloon tamponade is a temporary measure for uncontrolled variceal haemorrhage until endoscopy, transjugular intrahepatic portosystemic shunt (TIPS), or shunt surgery is available.[5]
Tamponade provides good control of bleeding in 90% of patients, although 50% will rebleed when the balloon is deflated. Despite being associated with serious complications (e.g., oesophageal ulceration, aspiration pneumonia) in up to 15% to 20% of patients, balloon tamponade can be a life-saving treatment in patients with massive uncontrolled variceal haemorrhage.[5]
TIPS is recommended if bleeding is not controlled by band ligation.[5][39][54]
If resources and expertise are available, early covered TIPS (<72 hours of active variceal bleed) can be considered in selected patients with:[5]
Child-Pugh class B cirrhosis and active bleeding
Child-Pugh class C cirrhosis with Child-Pugh score <14.[54] [ Child Pugh classification for severity of liver disease (SI units) Opens in new window ]
Patients who do not undergo early TIPS should continue on intravenous terlipressin or a somatostatin analogue (e.g., octreotide) for 2 to 5 days and then begin non-selective beta-blocker therapy once the vasoactive drug (i.e, terlipressin, a somatostatin analogue) is discontinued.[6] Rescue TIPS is indicated in these patients if haemorrhage cannot be controlled, or if bleeding recurs despite treatment with a vasoactive drug (e.g., terlipressin, octreotide) plus endoscopic variceal band ligation. Once TIPS is performed successfully, terlipressin or a somatostatin analogue can be discontinued.[6]
The National Institute for Health and Care Excellence in the UK recommends to consider Danis stent instead of balloon tamponade or early TIPS insertion (i.e., done within 72 hours) when:[55]
The patient does not respond to endoluminal therapy and their oesophageal varices are being considered for definitive treatment (until this treatment is done)
Definitive treatment is not appropriate and the patient is likely to be offered palliative care.
Studies indicate that Danis stent is better than the balloon tamponade device in controlling bleeding in the short term. The stent can stay in place for up to 7 days, whereas balloon tamponade needs to be removed after 24 to 36 hours. The use of Danis stent therefore affords more time to stabilise the patient and plan ongoing treatment options. Patients who have Danis stents do not need to stay in the intensive care unit (ICU), unless other aspects of their clinical condition require ICU care.[55][70][71][72]
Medium to large varices
Refer patients with varices to a gastroenterology service.[35]
A non-selective beta-blocker should be offered as first-line treatment for the prevention of bleeding for patients with cirrhosis and medium to large oesophageal varices, as recommended by the British Society of Gastroenterology (BSG).[5] Baveno VII (the European consensus meeting on portal hypertension) recommends propranolol, carvedilol, or nadolol as first-line agents.[29]
Local protocols should be followed for guidance on when to use endoscopic variceal band ligation. In practice, some UK experts follow the BSG guidelines, which recommend endoscopic variceal band ligation:[5]
For patients who are intolerant to non-selective beta-blockers, or when non-selective beta-blockers are contraindicated
If the patient chooses this as their preferred option.
However, bear in mind that recommendations from the National Institute for Health and Care Excellence (NICE) in the UK differ. NICE only recommends endoscopic variceal band ligation for the primary prevention of bleeding in patients with medium and large oesophageal varices.[17]
Band ligation of oesophageal varices for the primary prevention of bleeding reduces mortality, upper gastrointestinal bleeding, variceal bleeding, and serious adverse events compared with no intervention.[30] Note that band ligation cannot be done successfully in patients with small varices; it is only used in patients with medium to large varices.[30]
Small varices
Refer patients with varices to a gastroenterology service.[35]
Annual endoscopy should be offered to patients with cirrhosis and small varices, in line with recommendations from the BSG.[5]
If there is clear evidence of disease progression, the BSG recommends modifying the endoscopy intervals according to clinical need.[5]
The role of non-selective beta-blockers for the primary prevention of bleeding in patients with cirrhosis and small varices is unclear.[5][17][31][32][33] A large, triple blinded, multi-centre randomised controlled trial looking at non-selective beta-blockers versus placebo for the primary prophylaxis of variceal haemorrhage in these patients is ongoing.[34]
See the Primary prevention section for more information.
Patients with acute variceal haemorrhage are at high risk of rebleeding and therefore all need interventions for secondary prevention.
The British Society of Gastroenterology (BSG) defines variceal rebleeding as the occurrence of a single episode of clinically significant rebleeding from portal hypertensive sources from day 5.[5]
Clinically significant rebleeding is defined by the BSG as recurrent melaena or haematemesis alongside any of the following scenarios:[5]
Hospital admission
Blood transfusion
30 g/L drop in haemoglobin
Death within 6 weeks.
The BSG recommends the following for the secondary prevention of oesophageal variceal haemorrhage.[5]
A combination of a non-selective beta-blocker plus endoscopic variceal band ligation.[6][29][73][74][75] The Baveno VII consensus recommends propranolol, carvedilol, or nadolol as first-line non-selective beta-blockers.[29]
Non-selective beta-blockers or endoscopic variceal band ligation can be used in monotherapy as an alternative to combined treatment, taking into account the patient’s preferences and clinical judgement.
If non-selective beta-blockers alone are used, further endoscopy is not necessary unless clinically indicated.
Endoscopic variceal band ligation alone is an option to eradicate varices if there are contraindications or intolerance to combined use with a non-selective beta-blocker.
Varices should be banded at 2- to 4-weekly intervals until eradication in patients undergoing variceal band ligation. Once varices have been eliminated, an endoscopy should be performed at 3 months, and then every 6 months.
Recurrent varices should be treated with further endoscopic variceal band ligation until eradication.
Transjugular intrahepatic portosystemic shunt (TIPS) is recommended for patients who rebleed despite combined non-selective beta-blockers plus endoscopic variceal band ligation therapy or either intervention alone. TIPS can also be used based on patient choice.
TIPS with polytetrafluoroethylene (PTFE)-covered stents is recommended in preference to bare stents, as there is evidence that PTFE-covered stents are associated with a significantly higher primary patency rate and survival rate, and a significantly decreased rebleeding rate.[76]
In patients with Child-Pugh class A or B cirrhosis where TIPS is not feasible, shunt surgery can be used if the local expertise and resources are available.
BSG guidelines do not support the use of proton-pump inhibitors (unless required for the treatment of peptic disease), ‘prophylactic’ clotting or platelet support to reduce the risk of rebleeding.[5] Neither BSG nor BSH guidelines recommend the routine use of tranexamic acid or recombinant factor VIIa.[5][53] Studies have shown that high-dose tranexamic acid does not reduce mortality in patients with acute upper gastrointestinal bleeding.[53][77][78]
More info: Contraindications to TIPS placement
Absolute contraindications to TIPS placement include:[79]
Severe pulmonary hypertension (mean pulmonary pressure >45 mmHg)
Severe tricuspid regurgitation
Congestive heart failure
Severe liver failure
Polycystic liver disease
Active sepsis.
Relative contraindications to TIPS include:
Severe obstructive arteriopathy
Hepatic artery and coeliac trunk stenosis (preventing adequate sinusoidal perfusion by the hepatic artery)
Recurrent hepatic encephalopathy
Hepatocellular carcinoma and other liver tumours
Bile duct dilation.
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