Upper gastrointestinal bleeding (UGIB) is a common gastrointestinal (GI) emergency problem which present as Hematemesis in 40-50% , Melena in 70-80% , Hematochezia in 15-20% , Either hematochezia or melena in 90-98% , Syncope in 14.4% , Presyncope in 43.2% , Dyspepsia in 18% , Epigastric pain in 41% , Heartburn in 21% , Diffuse abdominal pain in 10% , Dysphagia in 5% , Weight loss in 12% and Jaundice in 5.2% of the patient. Knowing clinical presentation is very important to determine & identify the underlying cause (10).
Over ten thousand upper GI endoscopic evaluation was done over a period of 15 years from 1979 up to 1994 at black lion specialized hospital for an indication of dyspepsia (59.4%), upper gastrointestinal bleeding (18%) and liver disease (10.8%) which shows UGIB is one of the leading GI problem in our country (9).
After implementation of eradication therapy for Helicobacter pylori, prevention of esophageal variceal bleeding, use of low dose aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs ; prevalence of UGIB has changed.(11,12,13,14). H. pylori infection is one of the most common causes of peptic ulcer disease (PUD), and UGIB. In the developing countries in the last few years, due to improved sanitation, better diagnostic and therapeutic approaches, H. pylori infection related UGIB is decreasing. On the other hand usage of aspirin as a primary or secondary prevention in cardiovascular disease and NSAID in degenerative and musculoskeletal disease which increase with life expectancy has effect on its incidence, site of bleeding and age distribution. In addition vaccination against Hepatitis B virus, prophylactic using of propranolol, esophageal band ligation and liver transplantation has changed the incidence of esophageal variceal bleeding (11).
PUD complicated by bleeding is one of common cause of emergency based admission to hospital, and its estimated incidence is 20 to 60 per 100,000 person-years in the adult population(12); in United states it range from 48 to 160 per 100,000 and 19.4 to 57 individual per 100,000 individuals in Europe yearly (8).
Even though treatment of bleeding peptic ulcer disease is advanced; mortality associated with this disease doesn’t decrease with recent estimation of 5-10% (8,12, 13,14); this may be partly due to increasing number of aging population having PUD (currently more than 60 % of bleeding peptic ulcer patients are older than 60 years) (12).
Currently there is well established management principle for PUD related bleeding with pre endoscopic volume resuscitation, endoscopic hemostasis, and pre and post endoscopic treatment with high-dose intravenous proton pump inhibitors (PPI) which is effective in controlling acute bleeding, which may indicate deterioration or complications of pre-existing comorbidity is the most common cause of death, rather than continuous bleeding in patient with peptic ulcer bleeding (PUB) (8, 12, 13). Resuscitating the patient with intravenous fluids and blood component to reverse both hypovolemic shock and blood loss based on the patients clinical condition. Blood or blood products are recommended in patient with hemoglobin levels ?70 g/l (gram per litter) with a target hemoglobin level of 70–90 g/l, in the absence of comorbidity, in which the hemoglobin level indicated for transfusion is increased to a level of 10 g/l as in a patient with cardiorespiratory diseases to prevent decompensation. Insertion of nasogastric tube in high risk patient or administration of prokinetic agents (such as erythromycin infusion) can improve endoscopic visualization (8).
Six randomized controlled trials (RCTs) comprising 2223 participants with high risk ulcer who present with non-variceal bleeding post endoscopic intra venous PPIs decrease rebleeding, the need for repeat endoscopy or surgery, and mortality (8, 15,16); but pre endoscopic administration has no detectable effect on rebleeding, surgery, and mortality even if it may decrease need of endoscopic therapy initially(16).
Even though international guide line recommend endoscopic evaluation with in 24 hour, audit done in United Kingdom in 2007 shows only 50% of patients undergo endoscopic evaluation with in 24 hour of admission and 74% during their hospital stay; in Spain around 40 % of patient underwent endoscopic evaluation after 24 hour of admission. If endoscopic hemostasis failed surgery is an option of treatment especially in a patient with recurrent massive upper gastrointestinal hemorrhage requiring transfusion greater than 19 units of blood following initial endoscopic treatment; but for a patient older than 80 year arterial embolization is equally effective (8).
A randomized placebo-controlled trial done on 664 patient by administering bolus esomeprazole 80 mg intravenously over 30 min, followed by continuous infusion of 8 mg/h for 71.5 h then changed to esomeprazole 40 mg oral regimen for another 27 days following successful endoscopic hemostasis in patients with Forrest class Ia–IIb bleeding lesions shows significant reduction of rebleedig at 72 h (5.9% vs 10.3% ), at 7th day(7.2% vs 12.9%) and 30th day (7.7% vs 13.6%) in the esomeprazole group as compared to placebo group respectively with additional reduction of need for endoscopic retreatment and surgery and all-cause mortality (17). There is no adequate evidence currently to support the use of either oral PPIs or low-dose intravenous PPIs following endoscopic hemostasis (8).
Patients having PUB with comorbidity such as: cardiac disease has RR of death of 2.39 (95 % CI) ; those with respiratory diseases have RR of death of 2.43 (95 % CI); those with hepatic disease have RR of death of 4.04 (95 % CI);those with renal disease have RR of death of 5.34 (95 % CI); those with diabetes have RR of death of 1.63 (95 % CI and; those with malignancy has RR of death of 6.33 (95 % CI) as compared with those without these disease which indicate mortality RR in patient with renal disease, hepatic disease & malignancy was twice that of cardiovascular and respiratory disease, which was in turn about twice that observed for diabetes mellitus(12,18). Beside comorbidity outcome of patient with UGIB depend on characteristics of the patient, severity of bleeding, and available facility and care to control bleeding (19).
Aspirin is widely used worldwide at doses >325 mg daily as analgesic and anti-inflammatory agent, at low doses (75–325 mg daily) as antiplatelet drug to prevent cardiovascular diseases and even at lower doses to decreases risk of colorectal cancer; however due to its topical and systemic damaging effects on gastrointestinal mucosa it lead to GI bleeding which is higher in old age, male sex, ulcer history and usage of concomitant medication with NSAIDs, cyclooxygenase 2 selective inhibitors, corticosteroids or other antithrombotic agents (20).
One long-term prospective cohort study shows increased risk of major gastrointestinal bleeding, after use of regular aspirin greater than 325mg /week which was dose-dependent and greatest risk seen among women who used >14 tablets/ week and the relationships were similar among short-term (?5 years) and long term (>5 years) aspirin users, in contrary prolonging duration of aspirin use was not significantly associated with risk of gastrointestinal bleeding after adjusting for aspirin dose (21).
To reduce this GI effect concomitant administration of antisecretory agents such as PPIs and Helicobacter pylori eradication in patients with a history of ulcer (20) and using low dose aspirin as much as possible is recommended (21).
The most common lethal complication of cirrhosis arising following any form chronic liver disease is variceal bleeding (both esophageal and gastric varices) which account for 60–65% of the bleeding episode (3, 22), the remained 35-40% arise from other cause of bleeding just like general population (3). It is a real medical emergency in which bleeding spontaneously stop only in half of the patients and its outcome depend on severity of liver disease (Child– Pugh class and Meld score) with 6 week mortality of 0 and 40% among patient with Child– Pugh class A and C respectively. Other factor for early mortality are presence of active bleeding on admission, infection, portal vein thrombosis and an initial hepatic-venous portal gradient (HVPG) higher than 20 mmHg (3).
In managing patient with variceal bleeding stopping active bleeding and rebleeding with fast evaluation and resuscitation to maintain systemic blood pressure greater than 100 mmHg is important (3), but vigorous resuscitation can lead to increment of portal hypertension and worsen bleeding (22). Beside resuscitation restricted blood transfusion with target hemoglobin of 7 to 8 g/dl which can reduce further bleeding, rebleeding and complication rate, and increased survival is recommended in contrary to over or liberal transfusion which increase portal hypertension (3, 22). In addition administration of vasoactive substance such as terlipressin, octreotide, somatostatin, and vapreotide prior to endoscopy which is continued for 5 days can diminish mortality and achieves haemostasis in 80% of patients and prophylactic antibiotics such as Norfloxacilin 400 mg twice per day orally, ciprofloxacin 200mg twice per day intravenously if the patient can’t tolerate oral intake and ceftriaxone 1 gm per day in patient with advanced cirrhosis can reduce bacterial infections, early rebleeding and mortality (3, 22).
Upper GI endoscopic evaluation and therapy should be performed with in the first 12 h of admission if there is variceal bleeding preferably with band ligation which is better interims of controlling bleeding and rebleeding as compared to Sclerotherapy (3, 22).
Combined therapy with endoscopy and vasoactive medication has better outcome but if patient continue to bleed or rebleed or unstable balloon tamponade can be applied as a bridge therapy till salvage therapy with placement of trans jugular intrahepatic portosystemic shunt (TIPS) is done. Transplantation can also be considered as early as possible (3, 22).
Once active bleeding is controlled secondary prophylaxis with nonselective beta blocker (e.g. propranolol or nadolol) alone or in combination with mononitrate (e.g. isosorbide mononitrate) which are equally effective (no statistically significant difference seen) should be started prior to discharge from hospital. In addition endoscopic band ligation should be done every 7–14-day until varices obliterate then every 3 to 6 month to check for reappearance of varices and its treatment, but if HVPG drop to