Diagnosis and treatment of patients with gastrointestinal bleeding

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1 Current Anaesthesia & Critical Care (2004) 15, ARTICLE IN PRESS MEDICAL Diagnosis and treatment of patients with gastrointestinal bleeding C. Meaden, A.J. Makin* UK KEYWORDS Upper gastrointestinal bleeding; Mortality; Peptic ulceration; Proton pump inhibitors Summary Acute gastrointestinal haemorrhage is a common problem and accounts for approximately 300 admissions per year for an average size hospital in the UK. Peptic ulcer and gastritis account for most cases of upper gastrointestinal (UGI) bleeding and diverticular disease and angiodysplasia account for the majority of serious lower gastrointestinal (LGI) bleeding. UGI bleeding is more than twice as common and the mortality rate is more than twice as high as LGI bleeding. Patients at greatest risk are those aged over 65, with serious co-morbid illness, those with severe bleeds and those who haemorrhage while an inpatient for other reasons. For GI bleeding endoscopy is the most accurate diagnostic test and almost always allows treatment for both UGI and LGI bleeding. Gastric acid suppression with proton pump inhibitors reduces the risk of rebleeding and mortality from peptic ulcers. Bleeding due to portal hypertension is usually variceal and best managed with endoscopic band ligation. Glypressin reduces the mortality of variceal haemorrhage as do prophylactic antibiotics. Transvenous intrahepatic portosystemic shunting is the treatment of choice for uncontrolled variceal bleeding and balloon tamponade can provide a bridge to this. Angiography is occasionally needed for localization and treatment, particularly where the bleeding remains obscure after endoscopy. Surgery is required where other treatment modalities have failed, but every effort should be made to localize the cause of bleeding to reduce surgical mortality. & 2004 Published by Elsevier Ltd. Introduction Acute gastrointestinal (GI) bleeding is a common clinical problem. The incidence of acute upper GI bleeding ranges from 50 to 150 per population per year and is twice as common in men as women. 1 Acute lower GI bleeding is less common with an incidence of 20 per The *Corresponding author. Tel.: þ ; fax: þ address: alistair.makin@cmmc.nhs.uk (A.J. Makin). mortality rate from upper GI (UGI) bleeding in the UK is 11% in patients presenting to the hospital with a bleed but the mortality rate is three times as great where UGI bleeding develops during hospitalization. 1 These rates have remained stubbornly high despite the introduction of earlier therapeutic endoscopy and more accurate monitoring of highrisk patients. The mortality rate of acute UGI bleeding is correlated with age and the severity of co-morbid disease, as well as the cause of the bleeding. These factors have been unaffected by improvements in endoscopic and surgical /$ - see front matter & 2004 Published by Elsevier Ltd. doi: /j.cacc

2 124 C. Meaden, A.J. Makin treatments so that the number of truly preventable deaths may be quite small. 3 The mortality rate of lower GI bleeding is 3.6% and is markedly higher when the bleed occurs as in an inpatient setting compared to those who present with this problem. 2 The key factor in the management of acute GI bleeding is the assessment and adequate resuscitation of the patient. This must be achieved before diagnosis and specific therapy can be performed. Presentation and localization Bleeding from the UGI invariably presents with haematemesis and/or melaena. The vomitus can be bright red (fresh) or coffee ground (altered blood). Melaena consists of the passage of black tarry stools caused by bacterial degradation of haemoglobin and is generally due to UGI sources of bleeding, although small bowel and proximal colonic lesions can also be the cause. The passage of bright or dark red blood per rectum (PR) is usually due to a lower GI cause of bleeding, but can be the result of a brisk UGI bleed. In a study of patients presenting with significant PR bleeding, 11% were found to have an upper GI cause. 4 An elevated blood urea is another indication of an UGI source of the bleeding. This is partly due to degradation and absorption of haemoglobin and partly to hypovolaemic renal impairment. The severity of the bleed needs to be accurately assessed, as this will determine the urgency and nature of the patient s subsequent treatment. Patients with a large volume bleed can be confused, anxious or lethargic as well as tachycardic or hypotensive. 5 These signs generally indicate a blood loss of 40% (or 2000 ml) or greater. Lesser degrees of blood loss, which fail to cause hypotension, can be identified by falls in the postural blood pressure of 20 mmhg or more. The initial haemoglobin concentration is a poor indicator of the amount of blood lost because it does not fall until intravascular volume repletion has occurred from the extravascular space, which may take h. The amount of blood loss is better estimated from the pulse, blood pressure and clinical signs of ongoing blood loss such as haematemesis or melaena. Resuscitation The first priority is to correct fluid losses and to restore blood pressure. In the absence of liver disease a colloid or normal saline can be given initially. In the presence of liver disease a colloid or dextrose should be given initially. An adequately resuscitated patient has a central venous pressure of cm H 2 O and passes 0.5 ml/kg/h of urine. 5 Blood transfusion is almost always required where there is active bleeding with shock and when there is large volume haematemesis. Transfusion is generally reserved for those with a haemoglobin concentration is less than 10 g/dl when the bleeding is less severe. In some patients on intensive care wards, particularly in those with ischaemic heart disease, mortality increases the lower the haemoglobin falls below 10 g/dl, 6 although there is little conclusive information based on large clinical trials to determine the point at which it is safest to transfuse patients who have had a GI bleed. 7 Severity of acute upper GI bleeding The volume of blood lost is a key predictor of the severity of the bleed, but there are other factors which also predict mortality from the bleed; age, co-morbidity, the cause of the bleed and the endoscopic stigmata of the bleeding site. 1 Intuitively, elderly patients with serious co-morbidities (renal or liver failure or cancer) and those who bleed from malignancies of the upper GI tract have the highest death rates. High-risk patients should be fasted and then undergo an upper GI endoscopy after resuscitation, ideally within 12 h of presentation. Patients with organ failure requiring blood transfusion and those with major blood loss (30 40%) should have central venous pressure measurement and be managed on a critical care ward. This facilitates appropriate fluid replacement and gives an early indication of further bleeding. Patients should also have a measurement of their prothrombin time, particularly those with established or suspected liver disease and those who are therapeutically anti-coagulated in order to determine the presence of a correctable coagulopathy and over anti-coagulation. 3 Causes of acute upper GI bleeding The commonest cause of upper GI bleeding seen at endoscopy is peptic ulceration, which accounts for approximately 50% of cases where the cause of upper GI bleeding is identified. Other causes and their frequency are given in Table 1. 1 Although varices and bleeding from upper GI malignancy account for only 8% of cases (4% each) they account for 17% of deaths from upper GI haemorrhage.

3 Diagnosis and treatment of patients with gastrointestinal bleeding 125 Table 1 Incidence and mortality of upper GI bleeding by cause. 1 Final diagnosis Incidence (%) Mortality (%) Peptic ulcer Malignancy 4 37 Varices 4 23 Mallory Weiss 5 3 syndrome Gastritis 11 7 Oesophagitis 10 8 Other 6 18 None Table 2 Stigmata of haemorrhage and the risk of ulcer rebleeding. 12 Stigmata of haemorrhage Incidence (%) Rebleeding (%) Arterial bleeding Non-bleeding visible vessel Adherent clot (no visible vessel) Other stigmata No stigmata Peptic ulcer bleeding has remained the commonest cause of upper GI haemorrhage despite the use of effective acid suppressive medication. A number of factors are probably responsible for this including the increasing use of aspirin and other nonsteroidal anti-inflammatory drugs and the ability of ulcers to bleed without any prior symptoms. 8,9 Ulcers tend to occur on the lesser curve of the stomach and in the duodenal bulb where the anastamotic arterial blood supply is poor. Severe ulcer bleeding typically occurs when the ulcer base erodes through the wall of an artery. The gastroduodenal artery is closely related to the posterior inferior duodenal bulb and ulcers here are more likely to rebleed because of involvement of this artery. 10 Patients that rebleed or continue to bleed have a poorer outcome and a mortality rate of up to 30%. 11 The therapies available for treating upper GI bleeding include endoscopic, pharmacological, surgical and radiological and each will be discussed below. Endoscopic treatment of non-variceal upper GI bleeding Endoscopic stigmata have been defined which predict the rate of rebleeding from peptic ulcers (Table 2). Peptic ulcers with an actively bleeding vessel, a visible non-bleeding vessel, or a vessel with an overlying clot are at high risk of rebleeding and should be treated endoscopically which reduces the rebleeding rate, the need for surgery and mortality. 13 Ulcers with a clean base or haematin staining have low rebleed rates and can be managed medically. 12 Endoscopic therapy for bleeding ulcers is based on injection and heat application to the bleeding vessel. Adrenaline diluted to 1: is frequently used as injection therapy in the UK. It acts probably by a combination of vasoconstriction and vessel tamponade. Heat application through a monopolar or bipolar probe cauterizes the end of the bleeding vessel and while being as effective as injection therapy at achieving haemostasis it is associated with a higher risk of perforation. When both treatment modalities are used together they are more effective, particularly if the bleeding is arterial. 5 Endoscopic treatment of high-risk ulcers reduces the rate of rebleeding to 15 20% compared to the values in Table Pharmacological therapy for bleeding ulcers The results of intravenous acid suppression therapy for bleeding ulcers have demonstrated that proton pump inhibitor therapy, in particular omeprazole is superior to H 2 -receptor antagonists. The theoretical reason for this may be the ability of proton pump inhibitors to better suppress gastric acid secretion and stabilize clot formation. 15,16 The use of intravenous omeprazole following endoscopic treatment of a bleeding ulcer compared to oral omeprazole results in a significant reduction in the rate of recurrent bleeding from 22.5% to 6.7%. 17 There was also a reduction in the death rate from 10% to 4.2%, although this did not reach statistical significance. The evidence for the use of intravenous H 2 - receptor antagonists suggests that they may be of mild benefit in reducing the rate gastric ulcer rebleeding, but they have no effect on the rate of duodenal ulcer rebleeding (Figs. 1 and 2). 18 With the availability of proton pump inhibitors there is little to support the use of H 2 -receptor antagonists when required for intravenous use. Most patients who have bled from ulcers require oral rather than intravenous acid suppression. However, high dose oral proton pump inhibitors

4 126 C. Meaden, A.J. Makin Figure 1 A duodenal ulcer with a raised clot over a vessel. This is at high risk of rebleeding and should be treated endoscopically. eradicated to reduce the risk of rebleeding. 21 In those who have Helicobacter and are taking NSAIDs there is some evidence to suggest that eradication therapy in this group will also reduce the risk of further bleeding. If GI bleeding was a result of aspirin ingestion and there are strong grounds for restarting an anti-platelet agent once the ulcer has healed then clopidogrel should be used in preference to aspirin and if an NSAID needs to be used for analgesia then the least ulcerogenic should be used (ibuprofen) in combination with a proton pump inhibitor. 22 In those who have bled from an ulcer associated with Helicobacter it is important to confirm eradication, which is usually done noninvasively with a 13 C-urea breath test. In those who have bled from a gastric ulcer, unlike a duodenal ulcer, it is important to re-endoscope, usually after 6 weeks, to confirm healing and to exclude malignancy. Uncontrolled and recurrent non-variceal upper GI bleeding The management of rebleeding peptic ulcers has been investigated in a randomized controlled trial which compared repeat therapeutic endoscopy with emergency surgery. 23 There was no difference in the mortality rate between the groups. Surgery achieved haemostasis in 93% compared to 73% in the endoscopy, but at the cost of a 36% serious complication rate (including myocardial infarction, respiratory and renal failure) versus 14% for endoscopy. Repeat endoscopy for rebleeding should therefore be tried on one further occasion. If further bleeding occurs the decision to manage it endoscopically or surgically depends on the individual patient and the available endoscopic expertise. It must take into account the risk from a further episode of bleeding and the risk of urgent surgery. Elderly patients with co-morbid disease tolerate further bleeding least well. Figure 2 A small duodenal ulcer without any high-risk features. This should be managed medically. have been demonstrated to reduce the risk of recurrent ulcer bleeding even without endoscopic therapy. 19 The evidence for H 2 -receptor antagonists given orally suggests that if there is a beneficial effect it is relatively small. 20 Patients who bleed from peptic ulcers should receive a course of a proton pump inhibitor. If Helicobacter pylori is present this should be Management of variceal haemorrhage The mortality of acute variceal haemorrhage due to cirrhosis is approximately 30% and is closely related to the severity of the underlying liver disease. The most accurate predictive score of mortality is the Childs Pugh score which takes into account clinical (encephalopathy and ascites) and laboratory (prothrombin time, bilirubin and albumin) data. 24 As with other causes of upper GI haemorrhage the initial management is the resuscitation and

5 Diagnosis and treatment of patients with gastrointestinal bleeding 127 haemodynamic monitoring of the patient with endoscopy being performed when the patient is haemodynamically stable, although in severe bleeds this may not always be possible. The particular features of severe hepatocellular failure make variceal haemorrhage a complex management problem. Coagulopathy and thrombocytopenia are very common and sepsis occurs in approximately 20% of cirrhotic patients within 48 h of a variceal bleed. 25 With reference to the initial management prior to endoscopy elective tracheal intubation is more likely to be needed especially if encephalopathy is present or if there is prior hypoxaemia, which may be due to aspiration or pulmonary shunting, amongst other causes. (The raised intrathoracic pressure from assisted ventilation can reduce variceal pressure and haemorrhage prior to endoscopy.) At endoscopy the optimal treatment for bleeding oesophageal varices is band ligation and in expert hands this controls haemorrhage in over 90% of cases (Fig. 3). 26 Endoscopic sclerotherapy will also arrest variceal bleeding in the majority of cases and is technically easier to use particularly where there is continued haemorrhage impairing the view. Once endoscopic therapy has been given it is usual to give acid suppression in the form of a proton pump inhibitor. There are two main types of pharmacological therapies available for the treatment of active variceal bleeding. The first is vasopressin and its analogue glypressin and the other is somatostatin and its analogue octreotide. These drugs reduce Figure 3 Two large trunks of oesophageal varices. The risk of bleeding increases with the size of the varices. variceal bleeding by reducing portal pressure. The former achieves this by widespread vasoconstriction including that of the splanchnic circulation, which reduces portal blood flow and pressure. Somatostatin and its analogue octreotide cause selective splanchnic vasoconstriction and are associated with fewer systemic side-effects than vasopressin such as angina. 24 Vasopressin and glypressin have been shown to reduce active variceal bleeding when compared to placebo, as has somatostatin when given for 5 days, but there is no improvement in the control of bleeding with octreotide compared to placebo. In head to head trials of vasopressin or glypressin and somatostatin their efficacy at controlling bleeding is very similar. 24 The crucial difference between the drugs is that only glypressin has been shown to reduce the mortality from variceal bleeds. 27 In this trial it was administered to the patient in their home prior to their arrival in hospital. Whether the results are due to the drug or to the early administration is not clear, but on the available evidence glypressin should be the first choice agent. Balloon tamponade of variceal bleeding is effective at controlling bleeding, but bleeding tends to recur when the balloon is deflated and on its own it does not affect the mortality from the bleed. Its use is also complicated by frequent aspiration and occasional oesophageal rupture. 28 If bleeding has not been controlled by endoscopic and pharmacological means then balloon tamponade can be used until definitive treatment in the form of further endoscopy, transvenous intrahepatic portosystemic shunt (TIPSS) or oesophageal transection surgery can be arranged. TIPSS has been shown to be successful in stopping variceal bleeding which is not controlled endoscopically or pharmacologically. When compared to historical controls who underwent oesophageal transection for uncontrolled variceal bleeding the survival following TIPSS is at least as good. 24 Even if the bleeding is arrested the mortality remains high and is closely related to the severity of the underlying liver disease. The decision to intervene is complex and will in part be determined by whether the patient will ultimately be suitable for definitive treatment, in particular a liver transplant or has a potentially reversible cause for their disease such as alcohol. Under these circumstances TIPSS or surgery could be seen as providing a bridge to more definitive therapy. Bacterial infection is common around the time of variceal bleeding and it has been suggested that portal bacteraemia may be the triggering event in many variceal bleeds. 29 Prophylactic treatment

6 128 C. Meaden, A.J. Makin Causes of lower GI bleeds Figure 4 A Mallory Weiss tear. Bleeding almost always settles, but occasionally adrenaline injection is required. with a wide range of antibiotics (including ciprofloxacin, norfloxacin and amoxycillin/clavulanic acid) given enterally and intravenously significantly reduces mortality and should be part of standard treatment of variceal bleeding (Fig. 4). Angiography for GI bleeding Angiography is occasionally required in some cases for both the localization and treatment of GI bleeding. Such cases arise when the bleeding point is beyond endoscopic access, such as the small bowel, where endoscopic views are poor due to the severity of bleeding and where endoscopic treatment has failed and the patient is at high risk from surgical treatment. It can also be used after bleeding has stopped to detect the characteristic vascular patterns of arterio-venous malformations and tumours. 30 Angiographic embolization is most successful for arterial sources of bleeding, particularly in the upper GI tract. It can be used in the small and large bowel, although the risk of bowel infarction is higher here due poorer collateral blood supply. This risk is in addition to the risks of angiography itself. The higher complication rate of angiographic embolization limits its use to cases where endoscopic treatment has failed or is not appropriate and where surgical treatment is not appropriate due to the site of the bleeding or the patient s fitness for surgery. The approach to upper GI bleeds is summarized in Algorithm Lower GI bleeding usually presents with bright red blood PR or with maroon coloured blood that may be mixed with stool. This distinction is not absolute as severe upper GI bleeding can also present in this way. Conversely, bleeding from the right side of the colon can also present with melaena, which is more commonly due to upper GI bleeding. To distinguish between the two on stool colour is not always possible and one diagnostic approach is to perform an upper GI endoscopy first if the patient has bright or altered blood PR and signs of significant blood loss. An alternative approach is to pass a nasogastric tubefif blood is aspirated this confirms an upper GI bleeding source although the absence of blood does not exclude bleeding from the duodenum where blood may fail to reflux into the stomach. 32 However, if there are copious amounts of bile and no blood in the aspirate this virtually excludes an upper GI source. This approach correctly excludes upper GI bleeding in 94 98% of cases, but may miss lesions that are bleeding intermittently. The commonest causes of major lower GI bleeding are listed in Table 3 Diagnosis of lower GI bleeding A thorough attempt to localize the bleeding point prior to surgery is essential as the mortality rate of surgery is higher where the bleeding point was not localized before surgery. 33 Colonoscopy is the initial investigation of choice as it has a sensitivity of up to 80% for detecting the bleeding point, and allows therapy in many cases. This is best done with bowel preparation but can be done without and is a safe procedure with a very low complication rate (one diverticular perforation in 549 cases) providing the patient is adequately resuscitated first. 32 In addition to diagnosis colonoscopy can be used to treat the majority of the causes of lower GI bleeding and avoid the need for other treatments in most cases. Diverticular bleeding can be treated by injection therapy and thermal coagulation in the same way as peptic ulcers. Angiodysplasia is most commonly treated with argon plasma coagulation or injection therapy 34 (Fig. 5). Angiography may be used to detect an active bleeding source providing that the rate of bleeding is great enough. In those with acute bleeds the sensitivity of angiography was 47% in one series 35 which is typical of the results of other reports. 32

7 Diagnosis and treatment of patients with gastrointestinal bleeding 129 The complication rate of urgent angiography for lower GI bleeding may be as high as 11% 36 and includes contrast induced renal failure, dissection of the vessel wall and bowel infarction. Angiography should be reserved for those who have continued bleeding despite a negative colonoscopy and those with massive bleeding which prevents a diagnostic endoscopy. Radionuclide imaging, using radiolabelled red blood cells can be used to detect lower GI bleeding. It can detect lower rates of bleeding than angiography and because the imaging can occur

8 130 C. Meaden, A.J. Makin over several hours it can detect intermittent bleeding too. 30 The major drawback of the test is inaccurate localization of the bleeding point due to peristaltic movement of blood. In some studies this has led to inaccurate localization in 60% of cases. 30 In the investigation of lower GI bleeding radio-nuclide imaging can be used following a non-diagnostic colonoscopy when either angiography is not available or the rate of bleeding is so low Table 3 Diagnosis Final diagnoses of major lower GI bleeding. Diverticular disease 43 Angiodysplasia 20 Undetermined 12 Neoplasia 9 Colitis 9 Radiation 6 Ischaemic 2 Ulcerative 1 Other 7 Percent of total diagnosis that it is unlikely to be useful. 34 The approach to a patient with lower GI bleeding is summarized in Algorithm Small bowel bleeds Despite a logical approach to the investigation of a patient with GI bleeding the cause of the bleeding may remain obscure. One of the possible reasons for this is that the bleeding source is in the small bowel. The clinical presentation of this can be indistinguishable from other sources of bleeding. The commonest causes of this are angiodysplasia and small bowel tumours which can be primary or secondary. Other causes include ulcers, which are usually associated with NSAID use and a Meckel s Diverticulum, particularly in a young person. The approach to such a patient will be determined by the rate of bleeding. 31,34 If there is rapid blood loss then angiography is appropriate, but usually the bleeding is slower or has stopped. In this case further investigation should begin with endoscopy of either the upper or lower GI tract, depending on which has not yet been visualized. If this is

9 Diagnosis and treatment of patients with gastrointestinal bleeding 131 Figure 5 A colonic angiodysplatic vessel. It is commonest in the elderly. Figure 7 Haemorrhage from colonic Crohn s disease. This is occasionally torrential. Conclusions Figure 6 A colonic cancer. They can present with overt (in this cause) or occult bleeding. not diagnostic then enteroscopy to image the rest of the duodenum and part of the jejunum should be used as this can also therapeutic as well as diagnostic. If however this is not diagnostic then radionuclide imaging can be used if there is continued bleeding as can angiography, which has the advantage that it can detect characteristic vascular patterns of angiodysplasia and tumours even if they have stopped bleeding (Figs. 6 and 7). Upper and lower GI bleeding are common emergencies which have a significant mortality. This can be minimized by aggressive resuscitation, identification of those at highest risk and early access to diagnostic and therapeutic modalities. The key step in this process is adequate resuscitation as all other investigations and treatments are dependent on this. The first choice investigation for both upper and lower GI bleeding is endoscopy. It allows accurate diagnosis and specific treatment in the majority of cases. However there are times when endoscopy will be unsuccessful and it will be necessary to use other modalities such as angiography and surgery. This emphasizes the point that a multi-disciplinary team including the intensivist, gastroenterologist, radiologist and surgeon ideally manages significant GI bleeding. References 1. Rockall TA, Logan RF, Devlin HB, Northfield TC. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. Br Med J 1995;311(6999): Longstreth GF. Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol 1997;92(3): Rockall TA, Logan RF, Devlin HB, Northfield TC. Influencing the practice and outcome in acute upper gastrointestinal

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