Question 1

Created on Mon, 06/05/2017 - 21:42
Last updated on Sat, 07/08/2017 - 18:45
Pass rate: 50%
Highest mark: 7.0

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A 45-year-old male with a background of chronic liver disease is admitted to the Emergency Depattment (ED) with massive haematemesis secondary to gastric varices. He is managed with endoscopy and sclerotherapy.

List four other causes for massive haematemesis.    (10% marks)

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

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

Following initial stabilisation and control of bleeding, he deteriorates with a variceal re-bleed.

List the options for controlling the re-bleed AND, where appropriate, the relative advantages and disadvantages of these.          (50% marks)

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College answer

a) Causes
• Gastric or duodenal ulcer with bleeding visible vessel
• Dieulafoy's lesion (large exposed arteriole within gastric wall)
• Tear at gastro-oesophageal junction (Mallory Weiss)
• Aorto-duodenal fistula
• Eroding cancer into vessel (short gastric artery, splenic artery)

b) Rebleed likely if:
• Advanced age
• Unable to band all varices
• Gastric > oesophageal varices
• Severe coagulopathy due to liver disease or massive transfusion
• Severity of portal hypertension or liver disease
• Size of varices – larger higher risk
• Presence of red signs (localised reddish spots on the mucosal surface of the varix)

c) Drugs to reduce risk of re-bleed
• Octreotide/somatostatin
• Vasopressin / terlipressin +/- venodilator
• Tranexamic acid
• Oral Sucralfate (local anti-fibrinolytic effect)
• PPI infusion if concomitant ulcer bleeding
• Beta blockers e.g. propranolol if haemodynamics permit
• Short-term prophylactic antibiotics

d) Options for re-bleeding:
• Measure and fix coagulation, ongoing resuscitation


• Repeat endoscopy
   o Can be done in ICU although may be more appropriate in the operating theatre
   o Requires airway protection
   o Allows endoscopic variceal obturation or endoscopic variceal ligation


• TIPS to reduce portal pressure; risks of encephalopathy
   o Strategy of choice with initial treatment failure
   o May be contra-indicated in high MELD score
   o Complications of shunting blood away from liver and increased hepatic encephalopathy


• Balloon tamponade (Sengstaken, Minnesota)
   o Only useful in varices in the oesophagus or GO junction; not useful for gastric
   o Requires airway protection
   o Mucosal injury and necrosis


• Surgery
   o Ligation and resection of gastric vessels
   o Oesophageal venous ligation
      ▪ Requires luminal incision; high risk of breakdown in context of liver disease
      ▪ May not be available depending on local resources


• Balloon-occluded retrograde transverse obliteration (BRTO)
   o New technique and still undergoing evaluation
   o Increases portal hepatic blood flow and may be alternative for patients who may not tolerate TIPS
   o Obliterates spontaneous porto-systemic shunts and may aggravate portal hypertension
• Activated factor 7
   o Questionable efficacy
   o Highly pro-coagulant
   o May have a role in buying time to allow retrieval to a more specialised centre

Discussion

a) Other causes of haematemesis could include a whole range of differentials. Owing to the author's shameful obsession with structured classifications, this range can be divided into "blood is coming from the gut" and "blood is not coming from the gut but somehow has ended up in the gut". This was generated with the use of Oh's Manual, but contains conditions which are not listed in the canonic Chapter 42  (pp. 487,  "Acute  gastrointestinal  bleeding"  by Joseph  JY  Sung).

Bleeding of gastrointestinal origin 

  • Oesophageal sources:
    • Oesophageal varices (90% of varices)
    • Mallory-Weiss tears or Boerhaave's syndrome
    • Oesophagitis
  • Gastric sources
    • Gastric varices (10% of varices)
    • Peptic ulcers (75% of bleeding ulcers)
    • Portal hypertensive gastropathy
    • Gastritis
  • Duodenal sources
    • Duodenal ulcers (25% of bleeding ulcers)
    • Duodenitis
  • Anywhere
    • Arterio-venous malformation
    • Dieulafoy lesion 
    • Trauma, eg. swallowed sharp object
    • Iatrogenic, eg. following sphincterotomy or duodenal polypectomy
    • Malignancy

Bleeding of non-gastrointestinal origin 

  • Swallowed blood
    • Epistaxis
    • Haemoptysis
    • Blood swallowed during delivery (neonates)
    • Haemorrhage following dental surgery or facial trauma
  • Exotic causes
    • Innomino-oesophageal fistula or aorto-duodenal fistula

b) The college have listed causes of rebleeding which seem fairly logical, eg. "unable band everything" and "still coagulopathic". To this list, one might also add gastroenterological lazyness (delayed endoscopy increases re-bleeding risk  according to Chen et al, 2012). 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)

c) Pharmacological agents which can decrease the risk of rebleeding:

  • 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, but Tavakoli et al published on this 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. 

d) Options for controlling a re-bleed: whenever the college ask for something with a list of advantages and disadvantages, it is usually better to put it in a table. Thus:

Options for Controlling a Variceal Re-Bleed
Strategy Advantages Disadvantages
Medical resuscitation
  • It does not hurt to correct coagulopathy and resuscitate with fluid and blood products
  • If the venous pressure ends up too high, there will be more bleeding
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
     
     

Factor VIIa is also mentioned by the college in their answer, though they themselves moderate their enthusiasm by pointing out that it has "questionable efficacy". If one reads the papers (eg. Bosch et al, 2008) this would certainly seem correct (there was no effect on any primary endpoints). The mention of this option in the college answer is itself questionable, as it is promoted as an option for controlling a re-bleed even when trial results "do not support the routine use of rFVIIa in this setting". In protest, I did not add it to my table.

References

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.