Gastrointestinal bleeding: Difference between revisions

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===Peptic ulcers===
===Peptic ulcers===
Based on evidence from people with other health problems [[Crystalloid solution|crystalloid]] and [[Volume expander#Colloids|colloids]] are believed to be equivalent for peptic ulcer bleeding.<ref name=Overall2011/> [[Proton pump inhibitor]]s may reduce mortality in those with severe disease as well as the risk of re-bleeding and the need for surgery among this group.<ref name=PPI2007>{{cite journal|last=Leontiadis|first=GI|coauthors=Sreedharan, A, Dorward, S, Barton, P, Delaney, B, Howden, CW, Orhewere, M, Gisbert, J, Sharma, VK, Rostom, A, Moayyedi, P, Forman, D|title=Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding|journal=Health technology assessment (Winchester, England)|date=December 2007|volume=11|issue=51|pages=iii–iv, 1–164|pmid=18021578}}</ref> Oral and intravenous formulations may be equivalent; however, the evidence to support this is not great.<ref>{{cite journal|last=Tsoi|first=KK|author2=Hirai, HW |author3=Sung, JJ |title=Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding.|journal=Alimentary pharmacology & therapeutics|date=Aug 5, 2013|pmid=23915096|doi=10.1111/apt.12441|volume=38|issue=7|pages=721–8}}</ref> In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance.<ref>{{cite journal|last=Sreedharan|first=A|author2=Martin, J |author3=Leontiadis, GI |author4=Dorward, S |author5=Howden, CW |author6=Forman, D |author7=Moayyedi, P |title=Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding|journal=Cochrane database of systematic reviews (Online)|date=2010-07-07|issue=7|pages=CD005415|pmid=20614440|doi=10.1002/14651858.CD005415.pub3|editor1-last=Sreedharan|editor1-first=Aravamuthan}}</ref> The evidence for the inhibition of fibrinolysis with [[tranexamic acid]] is insufficient to recommend its use.<ref name=Overall2011/><ref>{{cite journal|last=Gluud|first=LL|coauthors=Klingenberg, SL, Langholz, E|title=Tranexamic acid for upper gastrointestinal bleeding|journal=Cochrane database of systematic reviews (Online)|date=2012-01-18|volume=1|pages=CD006640|pmid=22258969|doi=10.1002/14651858.CD006640.pub2|editor1-last=Gluud|editor1-first=Lise Lotte}}</ref> [[Somatostatin]] and [[octreotide]], while recommended for varicial bleeding, have not been found to be of general use for non varicial bleeds.<ref name=Overall2011/>
Based on evidence from people with other health problems [[Crystalloid solution|crystalloid]] and [[Volume expander#Colloids|colloids]] are believed to be equivalent for peptic ulcer bleeding.<ref name=Overall2011/> [[Proton pump inhibitor]]s may reduce mortality in those with severe disease as well as the risk of re-bleeding and the need for surgery among this group.<ref name=PPI2007>{{cite journal|last=Leontiadis|first=GI|coauthors=Sreedharan, A, Dorward, S, Barton, P, Delaney, B, Howden, CW, Orhewere, M, Gisbert, J, Sharma, VK, Rostom, A, Moayyedi, P, Forman, D|title=Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding|journal=Health technology assessment (Winchester, England)|date=December 2007|volume=11|issue=51|pages=iii–iv, 1–164|pmid=18021578}}</ref> Oral and intravenous formulations may be equivalent; however, the evidence to support this is not great.<ref>{{cite journal|last=Tsoi|first=KK|author2=Hirai, HW |author3=Sung, JJ |title=Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding.|journal=Alimentary pharmacology & therapeutics|date=Aug 5, 2013|pmid=23915096|doi=10.1111/apt.12441|volume=38|issue=7|pages=721–8}}</ref> In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance.<ref>{{cite journal|last=Sreedharan|first=A|author2=Martin, J |author3=Leontiadis, GI |author4=Dorward, S |author5=Howden, CW |author6=Forman, D |author7=Moayyedi, P |title=Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding|journal=Cochrane database of systematic reviews (Online)|date=2010-07-07|issue=7|pages=CD005415|pmid=20614440|doi=10.1002/14651858.CD005415.pub3|editor1-last=Sreedharan|editor1-first=Aravamuthan}}</ref> There is tentative evidence of benefit for [[tranexamic acid]] which inhibites clot breakdown.<ref>{{cite journal|last1=Bennett|first1=C|last2=Klingenberg|first2=SL|last3=Langholz|first3=E|last4=Gluud|first4=LL|title=Tranexamic acid for upper gastrointestinal bleeding.|journal=The Cochrane database of systematic reviews|date=21 November 2014|volume=11|pages=CD006640|pmid=25414987}}</ref> [[Somatostatin]] and [[octreotide]], while recommended for varicial bleeding, have not been found to be of general use for non varicial bleeds.<ref name=Overall2011/>


===Variceal bleeding===
===Variceal bleeding===

Revision as of 21:13, 9 December 2014

Gastrointestinal bleeding
SpecialtyGastroenterology Edit this on Wikidata

Gastrointestinal bleeding or gastrointestinal hemorrhage describes every form of hemorrhage (loss of blood) in the gastrointestinal tract, from the pharynx to the rectum. It has diverse causes, and a medical history, as well as physical examination, generally distinguishes between the main forms. The degree of bleeding can range from nearly undetectable to acute, massive, life-threatening bleeding.

Initial emphasis is on resuscitation by infusion of intravenous fluids and blood transfusion. Treatment with proton pump inhibitors, octreotide, and antibiotics may be considered in certain cases. Upper endoscopy or colonoscopy are generally considered appropriate to identify the source of bleeding and carry out treatment.

Signs and symptoms

Gastrointestinal bleeding can range from microscopic bleeding, where the amount of blood is such that it can only be detected by laboratory testing, to massive bleeding where bright red blood is passed and hypovolemia and shock may develop.

Blood that is digested may appear black rather than red, resulting in "coffee ground" vomitus or tarry stool called melena.[1]

Differential diagnosis

Gastrointestinal bleeding can be roughly divided into two clinical syndromes: upper gastrointestinal bleeding and lower gastrointestinal bleeding.[1] Types of causes include: infections, cancers, vascular disorders, adverse effects of medications, and blood clotting disorders.[1]

Upper gastrointestinal

Main article: Upper gastrointestinal bleeding

Upper gastrointestinal bleeding is from a source between the pharynx and the ligament of Treitz. An upper source is characterised by hematemesis (vomiting up blood) and melena (tarry stool containing altered blood). About half of cases are due to peptic ulcer disease.[2] Esophagitis and erosive disease is the next most common causes.[2] In those with liver cirrhosis 50–60% of bleeding is due to esophageal varices.[2] Approximately half of those with peptic ulcers have an H. pylori infection.[2] Other causes include: gastric or duodenal ulcers, Mallory-Weiss tears, cancer, and angiodysplasia.[1]

A number of medications are found to cause upper GI bleeds.[3] NSAIDs or COX-2 inhibitors increase the risk about fourfold.[3] SSRIs, corticosteroids, and anticoagulants may also increase the risk.[3] The risk with dabigatran is 30% greater than that with warfarin.[4]

Lower gastrointestinal

Main article: Lower gastrointestinal bleeding

Lower gastrointestinal bleeding is typically from the colon, rectum or anus.[1] Causes include: hemorrhoids, cancer, angiodysplasia, ulcerative colitis, Crohn's disease, and aortoenteric fistula.[1] It may be indicated by red blood per rectum, especially in the absence of hematemesis. Isolated melena may originate from anywhere between the stomach and the proximal colon.

Other

A number of foods and medications can turn the stool either red or black.[1] Bismuth found in many antacids may turn stools black as may activated charcoal.[1] Blood from the vagina or urinary tract may also be confused with blood in the stool.[1]

Diagnostic approach

Diagnosis is often based on direct observation of blood in the stool or vomit. This can be confirmed with a fecal occult blood test. Differentiating between upper and lower bleeding in some cases can be difficult. The severity of an upper GI bleed can be judged based on the Blatchford score[5] or Rockall score.[3] The Rockall score is the more accurate of the two.[3] As of 2008 there is no scoring system useful for lower GI bleeds.[3]

Clinical

Gastric aspiration and or lavage, where a tube is inserted into the stomach via the nose in an attempt to determine if there is blood in the stomach, if negative does not rule out an upper GI bleed[6] but if positive is useful for ruling one in.[7] Clots in the stool indicate a lower GI source while melana stools an upper one.[7]

Laboratory testing

Recommended laboratory blood testing includes: cross matching blood, hemoglobin, hematocrit, platelets, coagulation time, and electrolytes.[5] If the ratio of blood urea nitrogen to creatinine is greater than 30 the source is more likely from the upper GI tract.[7]

Imaging

A CT angiography is useful for determining the exact location of the bleeding within the gastrointestinal tract.[8] Nuclear scintigraphy is a sensitive test for detecting occult gastrointestinal bleeding when direct imaging with upper and lower endoscopies are negative. Direct angiography allows for embolization of a bleeding source, but requires a bleeding rate faster than 1mL/minute.[9]

Prevention

In those with significant varices or cirrhosis nonselective β-blockers reduce the risk of future bleeding.[10] With a target heart rate of 55 beats per minute they reduce the absolute risk of bleeding by 10%.[10] Endoscopic band ligation (EBL) is also effective at improving outcomes.[10] Either B-blockers or EBL are recommended as initial preventative measures.[10] In those who have had a previous varcial bleed both treatments are recommended.[10] With some evidence supporting the addition of isosorbide mononitrate.[11] Testing for and treating those who are positive for H. pylori is recommended.[3] Transjugular intrahepatic portosystemic shunting (TIPS) may be used to prevent bleeding in people who re-bleed despite other measures.[3]

Treatment

The initial focus is on resuscitation beginning with airway management and fluid resuscitation using either intravenous fluids and or blood.[5] A number of medications may improve outcomes depending on the source of the bleeding.[5]

Peptic ulcers

Based on evidence from people with other health problems crystalloid and colloids are believed to be equivalent for peptic ulcer bleeding.[5] Proton pump inhibitors may reduce mortality in those with severe disease as well as the risk of re-bleeding and the need for surgery among this group.[12] Oral and intravenous formulations may be equivalent; however, the evidence to support this is not great.[13] In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance.[14] There is tentative evidence of benefit for tranexamic acid which inhibites clot breakdown.[15] Somatostatin and octreotide, while recommended for varicial bleeding, have not been found to be of general use for non varicial bleeds.[5]

Variceal bleeding

For initial fluid replacement colloids or albumin is preferred in people with cirrhosis.[5] Medications typically include octreotide or, if not available, vasopression and nitroglycerin to reduce portal pressures.[10] Terlipressin appears to be more effective than octreotide, but it is not available in many areas of the world.[3][16] It is the only medication that has been shown to reduce mortality in acute variceal bleeding.[16] This is in addition to endoscopic banding or sclerotherapy for the varices.[10] If this is sufficient then beta blockers and nitrates may be used for the prevention of re-bleeding.[10] If bleeding continues then balloon tamponade with a Sengstaken-Blakemore tube or Minnesota tube may be used in an attempt to mechanically compress the varicies.[10] This may then be followed by a transjugular intrahepatic portosystemic shunt.[10] In those with cirrhosis antibiotics decrease the chance of re bleeding, shorten the length of time spent in hospital, and decrease mortality.[17] Octreotide reduces the need for blood transfusions[18] and may decrease mortality.[19] No trials of vitamin K have been conducted.[20]

Blood products

The evidence for benefit of blood transfusions in GI bleed is poor with some evidence finding harm.[21] In those in shock O-negative packed red blood cells are recommended.[1] If large amounts of pack red blood cells are used additional platelets and fresh frozen plasma (FFP) should be administered to prevent coagulopathies.[5] In alcoholics FFP is suggested before confirmation of a coagulopathy due to presumed blood clotting problems.[1] Some evidence supports holding off on blood transfusions in those who have a hemoglobin greater than 7 to 8 g/dL and only moderate bleeding.[5][22] If the INR is greater than 1.5 to 1.8 correction with fresh frozen plasma or prothrombin complex may decrease mortality.[5] Evidence of a harm or benefit of recombinant activated factor VII in those with liver diseases and gastrointestinal bleeding is not determined.[23] A massive transfusion protocol may be used, but there is a lack of evidence for this indication.[3]

Procedures

The Blakemore esophageal balloon used for stopping esophageal bleeds if other measures have failed

The benefits versus risks of placing a nasogastric tube in those with upper GI bleeding are not determined.[5] Endoscopy within 24 hours is recommended,[5] in addition to medical management.[24] A number of endoscopic treatments may be used, including: epinephrine injection, band ligation, sclerotherapy, and fibrin glue depending on what is found.[1] Prokinetic agents such as erythromycin before endocopy can decrease the amount of blood in the stomach and thus improve the operators view.[5] They also decrease the amount of blood transfusions required.[25] Early endoscopy decreases hospital and the amount of blood transfusions needed.[5] A second endoscopy within a day is routinely recommended by some[3] but by others only in specific situation.[22] Proton pump inhibitors, if they have not been started earlier, are recommended in those in whom high risk signs for bleeding are found.[5] High and low dose PPIs appear equivalent at this point.[26] It is also recommended that people with high risk signs are kept in hospital for at least 72 hours.[5] Those at low risk of re-bleeding may begin eating typically 24 hours following endoscopy.[5] If other measures fail or are not available, esophageal balloon tamponade may be attempted.[1] While there is a success rate up to 90%, there are some potentially significant complications including aspiration and esophageal perforation.[1]

Colonoscopy is useful for the diagnosis and treatment of lower GI bleeding.[1] A number of techniques may be employed including: clipping, cauterizing, and sclerotherapy.[1] Preparation for colonoscopy takes a minimum of six hours which in those bleeding briskly may limit its applicability.[27] Surgery, while rarely used to treat upper GI bleeds, is still commonly used to manage lower GI bleeds by cutting out the part of the intestines that is causing the problem.[1] Angiographic embolization may be used for both upper and lower GI bleeds.[1] transjugular intrahepatic portosystemic shunting (TIPS) may also be considered.[3]

Prognosis

Death in those with a GI bleed is more commonly due to other illnesses (some of which may have contributed to the bleed, such as cancer or cirrhosis), than the bleeding itself.[1] Of those admitted to a hospital because of a GI bleed, death occurs in about 7%.[3] Despite treatment, re-bleeding occurs in about 7–16% of those with upper GI bleeding.[2] In those with esophageal varicies, bleeding occurs in about 5–15% a year and if they have bled once, there is a higher risk of further bleeding within six weeks.[10] Testing and treating H. pylori if found can prevent re-bleeding in those with peptic ulcers.[5] The benefits versus risks of restarting blood thinners such as aspirin or warfarin and anti-inflammatories such as NSAIDs need to be carefully considered.[5] If aspirin is needed for cardiovascular disease prevention it is reasonable to restart it within seven days in combination with a PPI for those with nonvariceal upper GI bleeding.[22]

Epidemiology

Gastrointestinal bleeding from the upper tract occurs in 50 to 150 per 100,000 adults per year.[21] It is more common than lower gastrointestinal bleeding which is estimated to occur at the rate of 20 to 30 per 100,000 per year.[1] Risk of bleeding is more common in males, and increases with age.[1]

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u Westhoff, John (March 2004). "Gastrointestinal Bleeding: An Evidence-Based ED Approach To Risk Stratification". Emergency Medicine Practice. 6 (3).
  2. ^ a b c d e van Leerdam, ME (2008). "Epidemiology of acute upper gastrointestinal bleeding". Best practice & research. Clinical gastroenterology. 22 (2): 209–24. doi:10.1016/j.bpg.2007.10.011. PMID 18346679.
  3. ^ a b c d e f g h i j k l m Palmer, K (2008-10-10). "Management of acute gastrointestinal blood loss: summary of SIGN guidelines" (PDF). BMJ (Clinical research ed.). 337: a1832. doi:10.1136/bmj.a1832. PMID 18849311. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  4. ^ Coleman, CI (January 2012). "Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation". International journal of clinical practice. 66 (1): 53–63. doi:10.1111/j.1742-1241.2011.02809.x. PMID 22093613. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  5. ^ a b c d e f g h i j k l m n o p q r s Jairath, V; Barkun, AN (October 2011). "The overall approach to the management of upper gastrointestinal bleeding". Gastrointestinal endoscopy clinics of North America. 21 (4): 657–70. doi:10.1016/j.giec.2011.07.001. PMID 21944416.
  6. ^ Palamidessi, N; Sinert, R; Falzon, L; Zehtabchi, S (February 2010). "Nasogastric aspiration and lavage in emergency department patients with hematochezia or melena without hematemesis". Academic Emergency Medicine. 17 (2): 126–32. doi:10.1111/j.1553-2712.2009.00609.x. PMID 20370741.
  7. ^ a b c Srygley FD, Gerardo CJ, Tran T, Fisher DA (March 2012). "Does this patient have a severe upper gastrointestinal bleed?". JAMA. 307 (10): 1072–9. doi:10.1001/jama.2012.253. PMID 22416103.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Wu, LM (2010-08-21). "Usefulness of CT angiography in diagnosing acute gastrointestinal bleeding: a meta-analysis". World journal of gastroenterology : WJG. 16 (31): 3957–63. doi:10.3748/wjg.v16.i31.3957. PMC 2923771. PMID 20712058. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unflagged free DOI (link)
  9. ^ Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, Sinclair P; International Consensus Upper Gastrointestinal Bleeding Conference Group. (19 Jan 2010). "International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding". Ann Intern Med. Vol. 152, no. 2. pp. 101–13. doi:10.7326/0003-4819-152-2-201001190-00009. PMID 20083829.{{cite news}}: CS1 maint: multiple names: authors list (link)
  10. ^ a b c d e f g h i j k Cat, TB; Liu-DeRyke, X (September 2010). "Medical management of variceal hemorrhage". Critical care nursing clinics of North America. 22 (3): 381–93. doi:10.1016/j.ccell.2010.02.004. PMID 20691388.
  11. ^ Li, L; Yu, C; Li, Y (March 2011). "Endoscopic band ligation versus pharmacological therapy for variceal bleeding in cirrhosis: a meta-analysis". Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 25 (3): 147–55. PMC 3076033. PMID 21499579.
  12. ^ Leontiadis, GI (December 2007). "Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding". Health technology assessment (Winchester, England). 11 (51): iii–iv, 1–164. PMID 18021578. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  13. ^ Tsoi, KK; Hirai, HW; Sung, JJ (Aug 5, 2013). "Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding". Alimentary pharmacology & therapeutics. 38 (7): 721–8. doi:10.1111/apt.12441. PMID 23915096.
  14. ^ Sreedharan, A; Martin, J; Leontiadis, GI; Dorward, S; Howden, CW; Forman, D; Moayyedi, P (2010-07-07). Sreedharan, Aravamuthan (ed.). "Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding". Cochrane database of systematic reviews (Online) (7): CD005415. doi:10.1002/14651858.CD005415.pub3. PMID 20614440.
  15. ^ Bennett, C; Klingenberg, SL; Langholz, E; Gluud, LL (21 November 2014). "Tranexamic acid for upper gastrointestinal bleeding". The Cochrane database of systematic reviews. 11: CD006640. PMID 25414987.
  16. ^ a b Ioannou, G; Doust, J; Rockey, DC (2003). Ioannou, George N (ed.). "Terlipressin for acute esophageal variceal hemorrhage". Cochrane database of systematic reviews (Online) (1): CD002147. doi:10.1002/14651858.CD002147. PMID 12535432.
  17. ^ Chavez-Tapia, NC; Barrientos-Gutierrez, T; Tellez-Avila, F; Soares-Weiser, K; Mendez-Sanchez, N; Gluud, C; Uribe, M (September 2011). "Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding – an updated Cochrane review". Alimentary pharmacology & therapeutics. 34 (5): 509–18. doi:10.1111/j.1365-2036.2011.04746.x. PMID 21707680.
  18. ^ Gøtzsche, PC; Hróbjartsson, A (2008-07-16). Gøtzsche, Peter C (ed.). "Somatostatin analogues for acute bleeding oesophageal varices". Cochrane database of systematic reviews (Online) (3): CD000193. doi:10.1002/14651858.CD000193.pub3. PMID 18677774.
  19. ^ Wells, M; Chande, N; Adams, P; Beaton, M; Levstik, M; Boyce, E; Mrkobrada, M (June 2012). "Meta-analysis: vasoactive medications for the management of acute variceal bleeds". Alimentary pharmacology & therapeutics. 35 (11): 1267–78. doi:10.1111/j.1365-2036.2012.05088.x. PMID 22486630.
  20. ^ Martí-Carvajal, AJ; Cortés-Jofré, M; Martí-Peña, AJ (2008-07-16). Martí-Carvajal, Arturo J (ed.). "Vitamin K for upper gastrointestinal bleeding in patients with liver diseases". Cochrane database of systematic reviews (Online) (3): CD004792. doi:10.1002/14651858.CD004792.pub3. PMID 18677778.
  21. ^ a b Jairath, V; Hearnshaw, S; Brunskill, SJ; Doree, C; Hopewell, S; Hyde, C; Travis, S; Murphy, MF (2010-09-08). Jairath, Vipul (ed.). "Red cell transfusion for the management of upper gastrointestinal haemorrhage". Cochrane database of systematic reviews (Online) (9): CD006613. doi:10.1002/14651858.CD006613.pub3. PMID 20824851.
  22. ^ a b c Barkun, AN (2010-01-19). "International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding". Annals of internal medicine. 152 (2): 101–13. doi:10.1059/0003-4819-152-2-201001190-00009. PMID 20083829. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  23. ^ Martí-Carvajal, AJ (2012-03-14). Martí-Carvajal, Arturo J (ed.). "Human recombinant activated factor VII for upper gastrointestinal bleeding in patients with liver diseases". Cochrane database of systematic reviews (Online). 3: CD004887. doi:10.1002/14651858.CD004887.pub3. PMID 22419301. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  24. ^ D'Amico, G; Pagliaro, L; Pietrosi, G; Tarantino, I (2010-03-17). d'Amico, Gennaro (ed.). "Emergency sclerotherapy versus vasoactive drugs for bleeding oesophageal varices in cirrhotic patients". Cochrane database of systematic reviews (Online) (3): CD002233. doi:10.1002/14651858.CD002233.pub2. PMID 20238318.
  25. ^ Bai, Y (July 2011). "Meta-analysis: erythromycin before endoscopy for acute upper gastrointestinal bleeding". Alimentary pharmacology & therapeutics. 34 (2): 166–71. doi:10.1111/j.1365-2036.2011.04708.x. PMID 21615438. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  26. ^ Wu, LC (2010-05-28). "High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding: a meta-analysis". World journal of gastroenterology : WJG. 16 (20): 2558–65. doi:10.3748/wjg.v16.i20.2558. PMC 2877188. PMID 20503458. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unflagged free DOI (link)
  27. ^ "Management of acute lower GI bleeding". University of Pennsylvania Health System (UPHS). Jan 2009. p. 6.
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