Question 30

A 45-year-old male with a background of chronic liver disease is admitted to the Emergency Department with massive haematemesis secondary to a variceal bleed. He is managed with endoscopy and sclerotherapy.

a)    List the clinical indicators for risk of re-bleeding from the gastric varices.    (20% marks)

b)    List the pharmacological agents that may reduce the risk of a re-bleed.    (20% marks)

c)    Briefly discuss the haemoglobin transfusion trigger you will use in the clinical management of this patient    (20% marks)

d)    List, in order of priority, four specific non-pharmacological options for controlling variceal re-bleed AND, where appropriate, the relative advantages and disadvantages of these.
(40% marks)
 

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College answer

Not available.

Discussion

This question is very similar to Question 1 from the first paper of 2017.

a)    List the clinical indicators for risk of re-bleeding from the gastric varices.

From Augustine et al (2010), there are several features found to be strongly associated with "five-day failure", a composite endpoint consisting of re-bleeding and five-day mortality. All of these have been combined into this list:

  • Uncontrolled bleeding
    • Ongoing acute bleeding, or failure to control bleeding at initial endoscopy ("unable to band all varices")
    • Delay in the procedure
    • Number of bands which were used - according to Xu et al (2011), more than 6 bands is a bad sign
  • Severe liver disease
    • Severity of liver disease: Child-Pugh and MELD scores (even their individual components!)
    • A hepatic venous pressure gradient (HVPG) in excess of 20mmHg
    • Aetiology of cirrhosis (apparently some causes are associated with greater risk of rebleeding)
    • Portal vein thrombosis
  • Severe initial haemorrhage
    • High transfusion needs
    • Shock state
  • Endoscopic features
  • Laboratory features
    • Haematocrit
    • Platelet count
    • Coagulopathy (prolonged PT)

b)    List the pharmacological agents that may reduce the risk of a re-bleed.

  • Terlipressin (has been shown to decrease mortality)
  • Octreotide ( the next best choice after terlipressin)
  • Propanolol (might be helpful but the jury is still out).
  • Antibiotics - sepsis promotes the risk of variceal bleeding; literature demonstrates a benefit from antibiotics in this setting (the usual course is 7 days).
  • Tranexamic acid - mentioned by the college in their answer to Question 1 from the first paper of 2017, but Tavakoli et al published on this later in 2017 and they did not find any difference in rebleeding rate, nor any other outcome variable for that matter. The whole thing is very 80s. However, as the college answers are definitive, the savvy candidate would need to include this potentially pointless therapy in their answer.
  •  Proton pump inhibitors: but PPI infusion probably has no advantage over twice-daily dosing
  • Sucralfate is also mentioned by the college in their answer. The "local anti-fibrinolytic effect" is seen more in patients who have had sclerotherapy and then go on to bleed from post-sclerotherapy ulcers (i.e. no longer varices, but still technically a rebleed). This was reported upon by Brooks (1995). The specific benefit seems to be the result of sucralfate counteracting the pro-fibrinolytic effect of ethanolamine oleate, the specific sclerosant agent widely used in the 1990s. 

c)    Briefly discuss the haemoglobin transfusion trigger you will use in the clinical management of this patient   

A haemoglobin transfusion trigger is not usually the way one decides to give a transfusion, as the decision should be based on a series of clinical assessments and weighing the risks andbenefits of blood transfusion. There is not a lot of data to describe numerical transfusion thresholds in this population. One study which could help is Rockey (2014), where the authors reported better outcomes with a transfusion target of 70g/L vs. 90g/L.

d)    List, in order of priority, four specific non-pharmacological options for controlling variceal re-bleed AND, where appropriate, the relative advantages and disadvantages of these.

Repeat endoscopy
  • May be able to control previously unseen varices, or use a different technique to the previous attempt
  • May be able to use several techniques simultaneously (eg. band ligation, sclerotherapy and electrocautery)
  • Risk of anaesthetic in an already unstable patient
  • If the first attempt did not succeed, what makes you think the subsequent attempt will be any more successful
Balloon tamponade
  • Should be able to control blood loss from otherwise uncontrollable variceal bleeding by applying enough direct pressure
  • Poorly tolerated by the conscious patient
  • Use by non-experts can produce terrible complications (eg. oesophageal rupture, aspiration, etc)
  • May exacerbate bleeding by dislodging variceal bands from previously well-controlled varices
TIPS
  • Decreases the chances of treatment failure in refractory variceal bleeding (in one study, the probability of remaining bleed-free was 97% in the TIPS group and 50% in the pharmacotherapy group)
  • No effect on long-term outcomes
  • Increases the risk of hepatic encephalopathy
  • Requires expertise which is becoming scarce
  • May be impossible in the coagulopathic volume-depleted patient
Surgical control
  • Allows direct control of bleeding, eg. resection of the bleeding varices, or the construction of some sort of surgical shunt, eg. the Warren distal splenorenal shunt.
  • Healing will be poor
  • Future liver transplantation will likely be technically difficult if not impossible
  • So far nobody has demonstrated any mortality benefit from this

Balloon-occluded retrograde transverse obliteration (BRTO)

  • Destroys shunts, and thus increases portal venous pressure
  • Sclerosant used in this procedure may cause renal failure, anaphylaxis and pulmonary oedema

References

Rockey, Don C. "To transfuse or not to transfuse in upper gastrointestinal hemorrhage? That is the question." Hepatology 60.1 (2014): 422-424.

Oh's Intensive Care manual: Chapter 42  (pp. 487)  Acute  gastrointestinal  bleeding  by Joseph  JY  Sung

arcia-Tsao, Guadalupe, and Jaime Bosch. "Management of varices and variceal hemorrhage in cirrhosis." New England Journal of Medicine 362.9 (2010): 823-832.

García-Pagán, Juan Carlos, et al. "Early use of TIPS in patients with cirrhosis and variceal bleeding." New England Journal of Medicine 362.25 (2010): 2370-2379.

Vlavianos, P., et al. "Balloon tamponade in variceal bleeding: use and misuse."BMJ: British Medical Journal 298.6681 (1989): 1158.

Reverter, Enric, and Juan Carlos García‐Pagán. "Management of an acute variceal bleeding episode." Clinical Liver Disease 1.5 (2012): 151-154.

Ioannou, G. N., J. Doust, and D. C. Rockey. "Terlipressin in acute oesophageal variceal haemorrhage." Alimentary pharmacology & therapeutics 17.1 (2003): 53-64.

Corley, Douglas A., et al. "Octreotide for acute esophageal variceal bleeding: a meta-analysis." Gastroenterology 120.4 (2001): 946-954.

Reiberger, Thomas, et al. "Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol." Gut62.11 (2013): 1634-1641.

Hou, Ming‐Chih, et al. "Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial." Hepatology 39.3 (2004): 746-753.

Augustin, Salvador, Antonio González, and Joan Genescà. "Acute esophageal variceal bleeding: Current strategies and new perspectives." World J Hepatol 2.7 (2010): 261-274.

Chen, Ping-Hsien, et al. "Delayed endoscopy increases re-bleeding and mortality in patients with hematemesis and active esophageal variceal bleeding: a cohort study." Journal of hepatology 57.6 (2012): 1207-1213.

Kleber, Gerhard, et al. "Prediction of variceal hemorrhage in cirrhosis: a prospective follow-up study.Gastroenterology 100.5 (1991): 1332-1337.