How to treat acute variceal bleeding?

The goal of resuscitation is to preserve tissue perfusion. Volume restitution should be initiated to restore and maintain haemodynamic stability.

Packed red blood cell transfusions should be performed conservatively, with a target haemoglobin level between 7-8 g/dl, although transfusion policy in individual patients should also consider other factors such as cardiovascular disorders, age, haemodynamic status and ongoing bleeding.

Intubation is recommended before endoscopy in patients with altered consciousness and those actively vomiting blood.

Extubation should be performed as quickly as possible after endoscopy.

In suspected variceal bleeding, vasoactive drugs (terlipressin, somatostatin, octreotide) should be started as soon as possible and continued for 2-5 days.

Hyponatremia has been described in patients on terlipressin, especially in patients with preserved liver function. Therefore, sodium levels should be monitored.

Antibiotic prophylaxis is an integral part of therapy for patients with cirrhosis presenting with upper gastrointestinal bleeding and should be instituted from admission.

The risk of bacterial infection and mortality are very low in patients with Child-Pugh A cirrhosis, but more prospective studies are still needed to assess whether antibiotic prophylaxis can be avoided in this subgroup of patients.

Intravenous ceftriaxone 1 g/24 h should be considered in patients with advanced cirrhosis in hospital settings with high prevalence of quinolone-resistant bacterial infections and in patients on previous quinolone prophylaxis, and should always be in accordance with local resistance patterns and antimicrobial policies.

Malnutrition increases the risk of adverse outcomes in patients with cirrhosis and acute variceal bleeding (AVB) and oral nutrition should be started as soon as possible.

Airway manipulation, including use of a nasogastric tube, should be performed with caution because of the risk of pulmonary infection.

Proton pump inhibitors, when started before endoscopy, should be stopped immediately after the procedure unless there is a strict indication to continue them.

Six-week mortality should be the primary endpoint for studies on the treatment of AVB.

Five-day treatment failure is defined either by absence of control of bleeding or by rebleeding within the first 5 days.

Child-Pugh class C, the updated model for end-stage liver disease (MELD) score, and failure to achieve primary haemostasis are the variables most consistently found to predict 6-week mortality.

Child-Pugh and MELD scores are currently the most utilised severity scoring systems.

Following haemodynamic resuscitation, patients with suspected AVB should undergo upper endoscopy within 12 h of presentation. If the patient is unstable, endoscopy should be performed as soon as safely possible.

The availability of an on-call GI endoscopist proficient in endoscopic haemostasis and on-call support staff with technical expertise in the usage of endoscopic devices, enabling performance of endoscopy on a 24/7 basis, is recommended. Trainees performing the procedure must always be closely supervised by the GI endoscopist.

In the absence of contraindications (QT prolongation), pre-endoscopy infusion of erythromycin (250 mg IV 30-120 minutes before endoscopy) should be considered.

Patients with AVB should be managed in intensive or intermediate care units.

Ligation is the recommended form of endoscopic therapy for acute oesophageal variceal bleeding.

Endoscopic therapy with tissue adhesives (e.g. N-butyl-cyanoacrylate/thrombin) is recommended for acute bleeding from isolated gastric varices and type 2 gastro-oesophageal varices that extend beyond the cardia.

Endoscopic variceal ligation (EVL) or tissue adhesive can be used in bleeding from type 1 gastro-oesophageal varices.

Based on current evidence, haemostatic powder cannot be recommended as first-line endoscopic therapy for AVB.

Endoscopic therapy (argon plasma coagulation, radiofrequency ablation or band ligation for PHG and gastric antral vascular ectasia) may be used for local treatment of PHG bleeding.

All patients with AVB should undergo abdominal imaging, preferably contrast-enhanced cross-sectional imaging (CT or MRI) to exclude splanchnic vein thrombosis, HCC and to map portosystemic collaterals in order to guide treatment.

Pre-emptive TIPS with polytetrafluoroethylene (PTFE)-covered stents within 72 h (ideally <24 h) is indicated in patients bleeding from oesophageal varices and type 1/2 gastro-oesophageal varices who meet any of the following criteria: Child-Pugh class C <14 points or Child-Pugh class B >7 with active bleeding at initial endoscopy or HVPG >20 mmHg at the time of haemorrhage.

In patients fulfilling the criteria for pre-emptive TIPS, acute-on-chronic liver failure, hepatic encephalopathy at admission and hyperbilirubinemia at admission should not be considered contraindications.

In refractory variceal bleeding, balloon tamponade or self-expandable metal stents (SEMS) should be used as a bridge therapy to a more definite treatment such as PTFE-covered TIPS. SEMS are as efficacious as balloon tamponade and are a safer option.

Failure to control variceal bleeding despite combined pharmacological and endoscopic therapy is best managed by salvage PTFE-covered TIPS.

TIPS may be futile in patients with Child-Pugh ≥14 cirrhosis, or with a MELD score >30 and lactate >12 mmol/L, unless liver transplantation is envisioned in the short-term. The decision to perform TIPS in such patients should be taken on a case-by-case basis.

In patients with AVB and hepatic encephalopathy, bouts of hepatic encephalopathy should be treated with lactulose (oral or enemas).

In patients presenting with acute variceal bleeding (AVB), rapid removal of blood from the gastro- intestinal tract (lactulose oral or enemas) should be used to prevent hepatic encephalopathy.

Variceal bleeding is due to portal hypertension, and the aim of the treatment should be focused on lowering portal pressure rather than correcting coagulation abnormalities.

Conventional coagulation tests, namely, prothrombin time/international normalised ratio (PT/INR) and activated partial thromboplastin time, do not accurately reflect the haemostatic status of patients with advanced liver diseases.

In the AVB episode, transfusion of fresh frozen plasma is not recommended as it will not correct coagulopathy and may lead to volume overload and worsening of portal hypertension.

In the setting of AVB, there is no evidence that platelet count and fibrinogen levels are correlated with the risk of failure to control bleeding or rebleeding. However, in case of failure to control bleeding, the decision to correct the haemostatic abnormalities should be considered on a case-by-case basis.

Recombinant factor VIIa and tranexamic acid are not recommended in AVB.

In patients with AVB who are on anticoagulants, these should be temporarily discontinued until the haemorrhage is under control. Length of discontinuation should be individualised based on the strength of the indication for anticoagulation.

In patients with GOV2, type 1 isolated gastric varices, and ectopic varices, BRTO could be considered as an alternative to endoscopic treatment or TIPS, provided it is feasible (type and diameter of shunt) and local expertise is available, as it has been shown to be safe and effective.

Either endovascular or endoscopic treatment should be considered in patients with ectopic varices.

TIPS may be combined with embolisation to control bleeding or to reduce the risk of recurrent variceal bleeding from gastric or ectopic varices, particularly in cases when, despite a decrease in portosystemic pressure gradient, portal flow remains diverted to collaterals.

In patients with cirrhosis and PVT, management of AVB should be performed according to the guidelines for patients without PVT, when possible.

Initial conduct:

• 80mg of Omeprazole bolus for all patients
• Omeprazole 40 mg 12/12h Suspected portal hypertension Octreotide 100 mcg bolus +100 mcg BI 4/4h for 48h Or Terlipressin 2 mg+ 1 mg 4/4h for 48h
• Prefer Terlipressin in Hepatorenal Syndrome
  Ciprofloxacin or ceftriaxone (to prevent SBP regardless of the presence of ascites)
  Lactulone (2-3 soft bowel movements per day) Erythromycin or metoclopramide 20-120 min before EDA (Less need for new EDA to identify the bleeding focus)

Upper Digestive Endoscopy
It must be performed within 12 hours of presentation or as soon as possible after adequate resuscitation
Endoscopic Treatment:
Ligation is superior to sclerotherapy because it is less expensive and eradicates varicose veins more quickly with lower rates of rebleeding or complications.
In gastroesophageal varices, we prefer ligation, but in less accessible places, such as the gastric fundus, we use cyanoacrylate:
GOV1- Small curvature: Elastic bandage, Ethanolamine or Cyanoacrylate
GOV 2 – Large curvature/Bottom: Cyanoacrylate
IGV 1- Background: Cyanoacrylate
IGV 2 – Other locations: Cyanoacrylate

• Rebleeding: Cyanoacrylate

References:

Corrigendum to ‘Baveno VII – Renewing consensus in portal hypertension’ [J Hepatol (2022) 959-974] Journal of Hepatology, Vol. 77, Issue 2