Massive gastrointestinal haemorrhage

This chapter deals with the investigations and resuscitation of massive gastrointestinal bleeding, where by "gastrointestinal" one refers to "things that go wrong in the lumen". Bleeding that is intraperioneal or retroperitoneal is obviously going to be a very different thing and will require a separate chapter.

In terms of relevance for the CICM fellowship, massive GI bleeding is probably not a high-yield subject matter (even though it forms a major part of our daily workload). Historically, it has appeared in several SAQs:

  • Question 16 from the second paper of 2023, which was about the management options for lower GI bleeding.
  • Question 1 from the first paper of 2017, which was all about the causes and management of a massive variceal haemorrhage
  •  Question 1a and Question 1b from the second paper of 2001, where the college offered us an exsanguinating alcoholic. The real fun began when in the last part of the SAQ the wife asked whether he was going to survive (see Staging and prognosis of chronic liver disease in ICU)

The best references for this would probably have to be large society guidelines, rather than review articles. 

Causes of gastrointestinal bleeding

Question 1 from the first paper of 2017 asked for four causes of massive GI haemorrhage. There is a long possible list of such causes.  The list offered here was generated mainly using Oh's Manual, but contains conditions which are not listed in the canonic Chapter 42  (pp. 487,  "Acute  gastrointestinal  bleeding"  by Joseph  JY  Sung).

Anywhere

  • Arterio-venous malformation, eg. Dieulafoy vascular malformations
  • Trauma, eg. swallowing 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

Value of investigations in upper GI bleeding

Endoscopy is best. Barium investigations are useless. Why?

  • Barium swallow is useles in hypertensive gastropathy and gastritis/oesophagitis/duodenitis - you simply cannot see these
  • Endoscopically, it is easy to visualise the source of bleeding and treat it simultaneously
  • If one can visualise the source of bleeding, one can predict the risk of rebleeding:
  • Obvious bleeder: 85-90% risk of rebleeding
  • Obvious vessel: 35-55% risk of rebleeding
  • Clot: 30-40% risk of rebleeding
  • Reddish spot: 5-10% risk of rebleeding
  • Nothing found: 5% risk of rebleeding

Generally, postero-inferior duodenal wall ulcers and high lesser curve of stomach ulcers tend to rebleed most vigorously, owing to the presence of large arteries nearby.

In order to catch an upper GI bleeder on an angiogram, the rate of bleeding should be greater than 0.5ml/min.

A high risk patient needs urgent endoscopy

Identifying the high risk patient, whom to cart away to the endoscopy suite:

  • Syncope (indicates hemodynamic instability)
  • Hematemesis (indicates that the stomach is filling with blood)
  • Hypotension
  • Transfusion requirements in excess of 4 units of PRBCs over 12 hrs
  • Age over 60
  • Multiple comorbidities

If endoscopy fails, or there is evidence of perforation, the next move is surgery.

Nobody seems to agree precisely when to make this call. In general, if you are taking a patient to theatre for an emergency salvage surgery after an upper GI bleed, their mortality will be around 15-20%.

Definitive haemostasis in upper GI bleeding

For peptic ulcers:

  • Adrenaline injection - cheap, easy to learn, and effective
  • Heat coagulation - with the added risk of perforation
  • Clipping - no risk of perforation, but technically difficult in some sites

All these methods seem roughly equivalent in their effectiveness.

It is generally thought that the use of all three methods on the same lesion gives the greatest reduction in rebleeding risk.

For varices:

  • Haemostasis:
  • Reducing portal hypertension pharmacologically
  • Reducing portal hypertension invasively
    • TIPS procedure - the redistribution of blood from the portal circulation certainly reduces the presure in oesophageal varices, and prevents rebleeding. 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). However, it is a risky undertaking. It is typically reserved for patients who have failed all the other therapeutic approaches. By commiting to this course of action, you exhange sanity for hemostasis, and condemn the patient to a greatly increased risk of hepatic encephalopathy.
  • Surgical control - this means either the resection of the bleeding varices, or the construction of some sort of surgical shunt, eg. the Warren distal splenorenal shunt. This has never been demonstrated to improve survival, and certainly exposes the patient to a host of complications, most notable of which is the greatly increased difficulty of any future liver transplant procedures.

Risk factors for re-bleeding from varices

Question 1 from the first paper of 2017 asked specifically for "clinical indicators for risk of re-bleeding", which is a fancy way of asking for a list of risk factors. A good paper by Augustine et al (2010) actually presents an entire table of studies which investigated the various prognostic indicators which predict rebleeding in acute variceal haemorrhage. Re-bleeding in the case of many of these was rolled together into "5-day failure", a sort of composite endpoint together with mortality, which it obviously has some sort of effect upon. This was remixed into the following list of predictive features:

  • 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)

Prevention of rebleeding after endoscopy

For peptic ulcer disease:

  • Proton pump inhibitors
    • and it seems that PPI infusion has no advantage over twice-daily dosing
  • Histamine (H2) receptor blockers

Tranexamic acid plays no role - there is good evidence that it is ineffective.

In general, drugs can prevent rebleeding post endoscopy, but they usually play little role in massive haematemesis, and on their own are ineffective.

For bleeding varices:

  • Early endoscopic control: delayed endoscopy increases re-bleeding risk (Chen et al, 2012)- ideally, the bleed should be controlled within the first 12 hours, as this is associated with the best mortality 
  • Terlipressin is the drug of choice, and it has been shown to decrease mortality in variceal bleeding
  • Octreotide is the next best choice
  • Non-selective beta blockade might be helpful but the jury is still out.
  • 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)
  • Antibiotics: In the patients with chronic liver disease, antibiotic prophylaxis is indicated. Sepsis promotes the risk of variceal bleeding, and variceal bleeding promotes the risk of sepsis. 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.Tavakoli et al published on this in 2017- 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: again, PPI infusion probably has no advantage over twice-daily dosing
  • Sucralfate is also mentioned by the college in their answer to Question 1 from the first paper of 2017. 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. 

Lower gastrointestinal bleeding

For the purposes of having a firm definition, anything below the ligament of Treitz is taken as the "lower" tract.

Risk stratification

Unstable patients: BSG recommend you stratify according to "stable" or "unstable", on the basis of whether or not the patient is shocked, which means most ICU patients will be definition be in the "unstable" category. Weirdly, the BSG use the shock index to determine whether the patient is shock, which is a strange thing to do as nobody else really uses this measure for anything. In case the reader is wondering about this metric (having themselves never encountered or used it before), it is a value is calculated by dividing the heart rate by the systolic blood pressure, where an SI of >1.0 suggests haemodynamic instability. It is a metric which could theoretically give a reassuring number of 0.7 for a patient with a heart rate of 68 and an SBP of 48 mmHg. The ESGE guidelines statement instead suggests that "no single risk score should be used in isolation to predict adverse outcomes" and recommends a gestalt clinical assessment to determine risk. 

Value of investigations in lower GI bleeding

CT angiography  is the recommended investigation for the haemodynamically unstable GI bleeder, from both the BSG and the ESGE. It was not even mentioned in the stem of Question 16 from the second paper of 2023, presumably because there was no point in asking about this uncontroversial first step which everyone is in agreement on. The guidelines quote the sensitivity and specificity as 79 %–95 % and 95 %–100 %. The most important role for this is to identify the site of the bleeding so as to guide the decisions around endoscopy and angiography. 

First line colonoscopy is useless. You will never find the bleeder in that mess of blood and stool. Both the BSG and the ESGE seem to believe that unprepped colonoscopy in acute gastrointestinal bleeding is a waste of time. Both sources of guidelines agree that there is a role for colonoscopy at some stage during that admission, but not in the initial acute stages, unless the bleeder is very clearly localised by CT and is well-placed in some easily accessible area of the distal bowel. Rapid bowel prep (4–6 L of PEG solution within 3–4 hours, usually via NG tube because who could possibly), is also an option, with a view to perform colonoscopy within six or so hours. This unpalatable option may be viable where angioembolisation is not possible. Interestingly, both societies recommend upper GI endoscopy as the next stage, if CT has failed to identify an embolisable lower GI source of bleeding.

Angiography is the gold standard, as it can identify a bleeder 85% of the time, and allows one to launch a bunch of Gelfoam into the offending artery, thus putting an end to the bleeding.

In order to see the characteristic "blush" of contrast, you need to be bleeding at a rate of at least 0.5ml/minute. Time is generally accepted to be the most important factor determining outcome here, and both societies suggest the angio happen as soon as possible following the CTA (ESGE actually specify 60 minutes).

Tc-99 Red Cell Scan is a way of radiolabelling RBCs and observing where they go. Apparently, it is identifies a GI bleeder 80% of the time. However it is unlikely that this will be available within the timeframe required to control acute bleeding.

Definitive hemostasis in lower GI bleeding

Colonoscopy is the ideal treatment option for patients in whom the bleeding is minor, and who have been prepped sufficiently. It is probably the least invasive treatment option.

Angioembolisation is the best option for patients who are bleeding too rapidly to wait for bowel prep. In these people, the rate of bleeding - which makes endoscopy futile - also makes angiography more accurate. The societies are broad;y in agreement that haemodynamically unstable patients should undergo angioembilisation as soon as possible, with the UK guidelines showing a slightly higher preference for this modality. 

Surgery is the option of choice for diverticular disease, unmanageable polyps and malignancies, and in situations where AVMs or inflammatory bowel disease lesions are not amenable to endoscopic management. It is the option of last resort for patients with bleeding that could not be controlled by other methods. On one hand, definitive control of major bleeding can be achieved by bowel resection, and good samples can be collected intraoperatively to aid diagnosis (eg. of malignancy), but on the other hand it is a laparotomy in an unprepped and unstable patient, with all the attendant risks and morbidity. Risk of perforation, slow recovery, wound infection, etc - but also one needs to consider the possibility that the bit of the bowel they resect was not the one that was bleeding. Determining the source of endoluminal bleeding is actually rather challenging, and the surgeons do not always got it right. 

Balloon-occluded retrograde transverse obliteration (BRTO) is mentioned by the college in their answer to Question 1 from the first paper of 2017 as a "new technique and still undergoing evaluation", which is weird because we have been doing this since 1996 (Haruta et al). It is basically a technique whereby the interventional radiologist accesses a portosystemic shunt vein and inflates a balloon in it. Usually the gastric fundus varices drain into the left renal vein via a gastrorenal shunt, and that makes it all very convenient. With the balloon inflated, the radiologist can then inject sclerosant in a retrograde fashion into the the varix. Unfortunately, the usual sclerosant (ethanolamine oleate again) can cause anaphylaxis, renal failure and pulmonary oedema. Once the balloon is released, some sclerosant may make its way into the systemic circulation. This does not seem to impact much on outcomes, as  Park et al (2015) reviewed the evidence and had found this technique "safe and efficacious".

Factor VIIa is also mentioned by the college in their answer to Question 1 from the first paper of 2017, 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"

References

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

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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.

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Barer, David, et al. "Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding." New England Journal of Medicine308.26 (1983): 1571-1575.

Brooks, W. Scott. "Use of Sucralfate in Variceal Sclerotherapy-Induced Ulcerations." Sucralfate (1995): 323-331.

Haruta, Ikuko, et al. "Balloon-occluded retrograde transvenous obliteration (BRTO), a promising nonsurgical therapy for ectopic varices: a case report of successful treatment of duodenal varices by BRTO." American Journal of Gastroenterology 91.12 (1996).

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