Major Upper Gastrointestinal Bleeding Research Articles

Reduction of major gastrointestinal bleeding risk with proton pump inhibitor therapy in patients with atrial fibrillation receiving direct oral anticoagulant

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This research was supported by a grant from the Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC21C0028). Background In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), gastrointestinal bleeding (GIB) is itself a serious event for the patient, and it causes an increase in the thromboembolic risk caused by discontinuation of anticoagulation therapy. There are limited data on the benefit of preventive PPI use to reduce the risk of GIB in DOAC users. Methods We included patients with AF receiving DOAC from 2013 to 2020 based on the Korean Health Insurance Review and Assessment database. For comparison between patients with and without PPI, propensity score (PS) weighting method was used. Primary outcome was major GIB and secondary outcomes were major upper GIB and upper GIB requiring transfusion. Results A total of 171,494 patients were included (mean 72±10 years, mean CHA2DS2-VASc 4.3±1.8; 50,577 of rivaroxaban, 23,010 of dabigatran, 54,461 of apixaban, and 43,446 of edoxaban). Among the total population, 40% of patients were prescribed PPI and 55% of PPI users were prescribed low dose PPI. After PS weighting, patients with PPI were associated with lower risks of major GIB, major upper GIB, and upper GIB requiring transfusion than those without PPI (hazard ratio [95% confidence interval]; 0.816 [0.758-0.878], 0.834 [0.770-0.901], and 0.814 [0.734-0.902], respectively, Figure A). Patients with low dose PPI showed significant risk reduction for major GIB, major upper GIB, and upper GIB requiring transfusion than those without PPI (0.570 [0.515-0.632], 0.563 [0.505-0.628], and 0.505 [0.435-0.587], respectively). The protective effect of PPI was slightly different among DOAC types (Figure B). In the subgroup analyses, major GIB risk reduction of PPI co-therapy was more accentuated in patients older than 75 years and those with underlying GI disease or symptoms. Conclusion In this largest Asian cohort of patients with AF receiving DOAC, PPI co-therapy might be beneficial to reduce the risk of major GIB and upper GIB. This was consistently observed with low-dose PPI. The protective effect of PPI was more pronounced in the high bleeding risk patients.

Aspirin Thromboprophylaxis in Joint Replacement Surgery

Introduction. Total knee replacement (TKR) and total hip replacement (THA) surgeries have historically been felt to carry a high risk of post-operative venous thromboembolism (VTE) events thereby warranting anticoagulant prophylaxis. This risk however was based on composite endpoints in which asymptomatic DVT on venography, as opposed to symptomatic VTE or VTE-related mortality, constituted the majority of the events. Furthermore, current day orthopedic practices have likely led to a reduction in risk of VTE, thought to be 3-5% in the absence of prophylaxis. While the American College of Chest Physicians (ACCP) guidelines recommend the use of an anticoagulant for prophylaxis for all patients undergoing TKR and THR over aspirin, American Academy of Orthopaedic Surgeons (AAOS) guidelines classify patients without a prior history of VTE, and those not meeting their high risk criteria (significant cardiovascular disease; BMI > 40; smoking + DM + BMI > 35; and recent cancer) as low-risk; aspirin (325 mg twice daily) is a recommended alternative for post-operative VTE prophylaxis in these patients. As a result, many orthopedic surgeons in the US use aspirin for patients without major risk factors for VTE other than the surgery itself, accounting for over 40% joint replacement surgery cases in the US. The risk of symptomatic VTE in this patient population outside of small and primarily retrospective studies remains unknown. We conducted a prospective cohort study of patients receiving aspirin thromboprophylaxis following TKR and THR surgery at a large orthopedic specialty hospital to assess the risk of clinically symptomatic VTE and bleeding events. This is a preliminary analysis of planned total accrual of 500 subjects (assuming 2% VTE event rate in aspirin-treated patients, as compared to 1% in anticoagulant-treated, with alpha and beta error levels of 5% and 50%, respectively, and accounting for attrition rate of at least 10%). Methods. All TKR and THR patients prescribed aspirin for VTE prophylaxis by the surgical team and not on any anticoagulant medications were eligible for the study. Study subjects were identified and consented post-operatively prior to their hospital discharge. Enrolled subjects were followed for symptomatic VTE and bleeding events during their hospitalization, and then contacted at 30 and 90 days postoperatively for a telephone survey. Symptomatic VTE and bleeding events were captured using a questionnaire and outside records obtained to confirm VTE or major bleeding events. Three-month risk of symptomatic VTE and major bleeding events associated with aspirin thromboprophylaxis were estimated. Results. A total of 300 patients, 199 TKR and 101 THR, have been enrolled in this ongoing study so far. Table 1 shows the baseline characteristics of the patients. A total of 6 symptomatic VTE (4 pulmonary emboli, 1 proximal deep vein thrombosis (DVT) and 1 isolated-distal DVT) occurred during the follow up period. (3-month post-op VTE event rate of 2%). 3 events were diagnosed during hospitalization, whereas the remaining 3 occurred following hospital discharge (within 7-10 days). Bruising was a common side effect affecting nearly 3% of the patients, but major bleeding events were rare, only 1 major upper gastrointestinal bleeding, giving a 3-month risk of 0.33%. There were no surgical bleeds reported. Conclusions. In this single-center prospective cohort study of TKR and THR patients considered to be at lower risk for VTE, the use of aspirin for thromboprophylaxis was associated with a 2% symptomatic VTE event rate over three months of follow up with minimal bleeding risk. This result, together with those of the EPCATII study from Canada showing that low-dose aspirin was as effective (~0.7% event rate) following 5 days of rivaroxaban following TKR and THR in lower risk patients, argues for a large randomized trial evaluating aspirin as monotherapy for VTE prophylaxis in such patients. Disclosures No relevant conflicts of interest to declare.

PWE-150 Anaesthetic Support and Theatre Access for Emergency Endoscopy in Major Upper Gastrointestinal Bleeding (UGIB); Where Can We Improve?

Introduction The 2015 NCEPOD “Time to get control” report recommends that hospitals admitting patients with severe UGIB have access to critical care and anaesthetic support for urgent endoscopy. We examined our emergency pathway including theatre urgency codes, time to therapy and clinical outcomes. Methods We analysed all patients who had emergency endoscopy in theatre for suspected severe UGIB at Queen’s Medical Centre, Nottingham, UK, between 1st March 2014 and 28th February 2015. We examined patient demographics, ASA and UGIB risk scores, shock index (SI; heart rate/systolic BP), referral times to endoscopy and breach rates, anaesthetic and operator details, endoscopic findings and therapy (blood product use, interventional radiology and surgery), procedural documentation, re-bleed plans, discharge location, complications and inpatient mortality. Results 95 patients (60 male mean [±SD] age 59.2 [±19.1]; 35 female, 55.2 [±28.4]) with suspected severe UGIB were treated in emergency theatres over the 12 month period. 93/95 (98%) had significant UGIB; 82% ASA grade ≥3 and Glasgow Blatchford Scores (GBS) were recorded in 18% of cases; median (range) score 12 (1–19). 64% were classified as theatre urgency 1 (U1; within 60 mins) and 25% U3 (within 180 mins). 64% of those in U1 had a high shock index (SI > 0.9). However, median time from referral to endoscopy was 215 (range 37–1370) minutes. 47% breached the theatre urgency code times; including 59% of those assigned to U1. A consultant gastroenterologist was present in theatre in 86/95 (91%) of cases and 96% of patients received a general anaesthetic with rapid-sequence induction. The UGIB was non-variceal in 55/95 (58%; endoscopic intervention in 63%), variceal in 32/95 (34%), no cause found 8/95 (8%). 70% received a blood transfusion within 24 hrs of admission, mean 2.7(±2.5) units packed cells. 9/95 (10%) had CT angiography and 6/95 (6%) underwent coil embolization. No patients underwent surgery. An endoscopy report was generated for all cases, but re-bleed plans were only documented in 51%. Following endoscopy, 63/95 (67%) required a high-dependency bed and inpatient mortality was 21%. Conclusion Patients undergoing emergency endoscopy in theatre for acute UGIB had high risk scores and inpatient mortality, but 47% breached theatre urgency timings. These delays may impact on patient outcomes and are likely multifactorial. Potential reasons include time for resuscitation, transfer from admitting areas and co-ordination of emergency endoscopy teams and equipment. These logistics need to be understood more and improved to achieve improvements in patient care. Disclosure of Interest None Declared

Use of the Over-The-Scope Clip for treatment of refractory upper gastrointestinal bleeding: a case series

The Over-The-Scope Clip (OTSC; Ovesco, Tübingen, Germany) is a novel endoscopic clipping device designed for tissue approximation. The device has been used in the closure of fistulas and perforations. We hereby report on a series of patients in whom OTSCs were used for endoscopic control of refractory or major upper gastrointestinal bleeding from lesions in the gastroduodenal tract between 1 July and 31 December 2012. Nine patients were included (median age 72.5 years, range 39 - 91) with bleeding gastric ulcers (n = 2), bleeding duodenal ulcers (n = 5), bleeding gastrointestinal stromal tumor in the stomach (n = 1), and bleeding from ulcerative carcinoma of the pancreas (n = 1). The median size of the ulcers was 2.5 cm (range 1 - 4). Six of the nine patients had undergone previous endoscopic hemostasis. Technical success was achieved in all patients and the clinical effectiveness was 77.8 %. The OTSC is a safe and effective method of endoscopic hemostasis for major bleeding from miscellaneous upper gastrointestinal causes and should be considered in patients with refractory bleeding after failure of conventional methods of endoscopic hemostasis.

Approach to a Child with Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding (UGIB) is a potentially life threatening medical emergency requiring an appropriate diagnostic and therapeutic approach. Therefore, the primary focus in a child with UGIB is resuscitation and stabilization followed by a diagnostic evaluation. The differential diagnosis of UGIB in children is determined by age and severity of bleed. In infants and toddlers mucosal bleed (gastritis and stress ulcers) is a common cause. In children above 2 y variceal bleeding due to Extra-Hepatic Portal Venous Obstruction (EHPVO) is the commonest cause of significant UGIB in developing countries as against peptic ulcer in the developed countries. Upper gastrointestinal endoscopy is the most accurate and useful diagnostic tool to evaluate UGIB in children. Parenteral vitamin K (infants, 1-2 mg/dose; children, 5-10 mg) and parenteral Proton Pump Inhibitors (PPI's), should be administered empirically in case of a major UGIB. Octreotide infusion is useful in control of significant UGIB due to variceal hemorrhage. A temporarily placed, Sengstaken-Blakemore tube can be life saving if pharmacologic/ endoscopic methods fail to control variceal bleeding. Therapy in patients having mucosal bleed is directed at neutralization and/or prevention of gastric acid release; High dose Proton Pump Inhibitors (PPIs, Pantoprazole) are more efficacious than H2 receptor antagonists for this purpose.

Glomus Tumor of the Stomach: A Rare Cause of Upper Gastrointestinal Bleeding

Introduction. Glomus tumors (GTs) are benign neoplasm originating from the glomus body, commonly described in subungual region. The involvement abdominal is rare. Our aim is to describe a case of glomus tumor of the stomach that presented upper gastrointestinal bleeding. A 34-year-old woman was admitted with upper gastrointestinal bleeding and underwent an upper endoscopy that showed bleeding arising from an ulcerated lesion, treated by sclerosis therapy. A new endoscopy confirmed a submucosal lesion in upper portion of the stomach. During the laparotomy, a tumor at the upper anterior wall of gastric body was found and resected by a vertical gastrectomy. The pathological exam revealed hyperplastic smooth muscle fibers of the muscularis propria of the stomach wall, surrounded by hyaline stroma. The immunohistochemistry panel was positive for smooth muscle actin and type IV collagen, with low rate of mitosis studied by Ki-67 which allowed the final diagnosis of a gastric glomus tumor. Discussion. The majority of intraperitoneal glomus tumors occur in the stomach, and it is phenotypically similar to those localized in peripheral sites. Gastric GT generally is a benign tumor although it can be malignant and have the potential to metastasize. Conclusion. Even though gastric glomus tumor is rarely described, it should be considered as a possible cause of a major upper gastrointestinal bleeding.

Recombinant activated coagulation factor VII (rFVIIa) as an adjunctive hemostatic therapy in patients with multiple system organ failure and acute upper gastrointestinal bleeding

Major upper gastrointestinal bleeding leads to increased length of stay and increased risk of death among critically ill patients [1]. Despite recent developments in prophylaxis, large randomized trials have not shown a decrease in mortality. Patients with multiple system organ failure (MSOF) accompanied by coagulopathy are among those with high risk for clinically important major gastrointestinal bleeding. The combination of increased risk of gastrointestinal lesions and coagulopathy makes this population of critically ill extremely vulnerable once the bleeding begins. Recombinant activated factor VII (NovoSeven®; Novo Nordisk, Denmark) has recently been used to reduce bleeding complications and to control bleeding in hemophilic patients [2], and also in cases of intractable postsurgical intra-abdominal hemorrhage and traumatic bleeding. Fifteen surgical and nonsurgical patients with clinically significant gastrointestinal bleeding and MSOF (Simplified Acute Physiology Score II between 53 and 69 points) were enrolled in this study. All patients had different types and degrees of coagulation abnormalities before the bleeding episode as a part of their MSOF. After the onset of bleeding all patients required fluid resuscitation, red blood cell transfusion, fresh frozen plasma and platelet concentrates, and in 73% we used inotropes and pressors to support the failing circulation. The initial bleeding rate among patients was between 14 and 22 ml/min. After the bleeding was considered clinically significant we used a single standard intravenous dose of rFVIIa along with other standard accepted therapeutic measures, including endoscopy. Bleeding decreased after this first dose of rFVIIa and ceased within a period of 18–110 min, with progressive return of coagulation parameters to near pre-bleeding values. Four patients required a second dose of rFVIIa. There were no thromboembolic adverse effects and recurrent episodes of bleeding within the first 5 days after the bleeding episode. We concluded the successful use of rFVIIa in patients with MSOF and acute upper gastrointestinal bleeding, when this hemostatic agent could compensate for MSOF-related coagulation abnormalities. Further large studies are needed to assess the efficacy of rFVIIa use and its relationship with possible decreased transfusion requirements in such patients.

Risk of upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases.

Most patients with vascular-occlusive diseases benefit from low-dose aspirin (75-325 mg/day). However, they have an increased risk of upper gastrointestinal bleeding (UGIB). To analyse the incidence and factors influencing the occurrence of UGIB in patients taking low-dose aspirin for the prevention of cardiovascular diseases outside clinical trials. We studied 903 consecutive patients discharged on low-dose aspirin from the Cardiology Department of a general hospital. Data were collected from medical charts and structured telephone interviews. Forty-one patients (4.5%) presented with UGIB requiring hospitalization during follow-up (45 +/- 22 months). The incidence of UGIB was uniform during follow-up (1.2 UGIB per 100 patient years). Multivariate analysis showed that a history of peptic ulcer or UGIB [risk ratio: 3.1, 95% CI: (1.5-6.5)] and aspirin dose (per 100 mg/day) [1.8 (1.5-2.9)] was associated with higher risk of UGIB. On the other hand, antisecretory [0.22 (0.07-0.75)] and nitrovasodilator drugs [0.73 (0.55-0.96)] were associated with a decreased risk. Cardiovascular patients on long-term low-dose aspirin have a stable risk of major UGIB, which is higher than published controlled clinical trials. Antisecretory and nitrovasodilator drugs protect from UGIB, whereas previous peptic ulcer or UGIB and higher doses of aspirin increase the risk.

The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption

OBJECTIVE: Major upper gastrointestinal bleeding (UGIB) is the most important adverse effect of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Alcoholic beverages also precipitate UGIB. This analysis was conducted to evaluate whether the deleterious effects of NSAIDs are further increased among drinkers. METHODS: An interview-based, case-control study was conducted in the U.S. and Sweden; 1224 patients hospitalized with acute major UGIB due to newly occurring peptic ulcer or gastritis were compared to 2945 neighbor controls. RESULTS: Compared with those who drank less than one drink/wk, the relative risk of acute UGIB increased with increasing alcohol consumption, rising to 2.8 among those who drank ≥21 drinks/wk. Among current drinkers, the relative risk of acute UGIB due to the use of aspirin was raised at all levels of alcohol consumption; the estimate for aspirin taken at least every other day (regular use) at doses of >325 mg among all current drinkers combined was 7.0; for regular use at lower doses, the corresponding estimate was 2.8, and for any occasional use, it was 2.4. All estimates were statistically significant. Data for ibuprofen were more limited, but the relative risk estimates did not appear to vary consistently with level of alcohol consumption. For regular use (all doses combined), the estimate among all drinkers combined was significantly elevated, at 2.7; occasional ibuprofen use was not associated with UGIB (1.2). There were insufficient data to evaluate other NSAIDs according to alcohol consumption. CONCLUSIONS: The findings suggest that acute UGIB is similarly associated with the use of the two most common nonprescription NSAIDs, aspirin and ibuprofen, at all levels of alcohol consumption. As heavy alcohol intake independently increases the risk, the incidence of UGIB is highest among persons who are both heavy drinkers and users of aspirin or ibuprofen.

Clinical Aspects of Upper Gastrointestinal Bleeding Associated With the Use of Nonsteroidal Antiinflammatory Drugs

The aim of this study was to compare the clinical features of major upper gastrointestinal bleeding among patients exposed to nonsteroidal antiinflammatory drugs (NSAID) and those not taking these drugs. Using data from a multicenter international case-control study designed to evaluate the role of drugs in the etiology of major upper gastrointestinal bleeding (UGIB), patients with a confirmed first episode of major UGIB were divided into two groups: those exposed to NSAIDs during the week before the onset of bleeding, and those not exposed. The groups were compared according to age and sex, clinical appearance and site of the bleeding, preceding symptoms, and requirement for transfusion and acute surgery. The median age was significantly higher and the proportion of women was slightly higher among the NSAID users. There was no significant difference between users and nonusers according to the clinical presentation, the site of the bleeding, or the frequency of preceding symptoms. Forty percent in each group had no symptoms before the onset of bleeding. Slightly more NSAID users received blood transfusions, although the same median amount of blood per transfusion was given in both groups. There was no difference in the frequency of surgical intervention. There are no important differences in the clinical presentation of major UGIB according to whether or not an individual is an NSAID user. An important finding is the frequent absence of preceding symptoms in patients with major UGIB, regardless of NSAID use.

Clinical aspects of upper gastrointestinal bleeding associated with the use of nonsteroidal antiinflammatory drugs

Objective: The aim of this study was to compare the clinical features of major upper gastrointestinal bleeding among patients exposed to nonsteroidal antiinflammatory drugs (NSAID) and those not taking these drugs. Methods: Using data from a multicenter international case-control study designed to evaluate the role of drugs in the etiology of major upper gastrointestinal bleeding (UGIB), patients with a confirmed first episode of major UGIB were divided into two groups: those exposed to NSAIDs during the week before the onset of bleeding, and those not exposed. The groups were compared according to age and sex, clinical appearance and site of the bleeding, preceding symptoms, and requirement for transfusion and acute surgery. Results: The median age was significantly higher and the proportion of women was slightly higher among the NSAID users. There was no significant difference between users and nonusers according to the clinical presentation, the site of the bleeding, or the frequency of preceding symptoms. Forty percent in each group had no symptoms before the onset of bleeding. Slightly more NSAID users received blood transfusions, although the same median amount of blood per transfusion was given in both groups. There was no difference in the frequency of surgical intervention. Conclusions: There are no important differences in the clinical presentation of major UGIB according to whether or not an individual is an NSAID user. An important finding is the frequent absence of preceding symptoms in patients with major UGIB, regardless of NSAID use.

Diagnostic pitfalls and therapeutic strategies in the treatment of pancreatic duct haemorrhage.

Haemorrhage via the pancreatic duct, a rare cause of upper gastrointestinal bleeding (GIB), often poses a diagnostic dilemma. We analysed our experience with 10 patients (8 men, 2 women; mean age 44 years, range 34 – 62) treated during a 12 year period. All had a history of alcohol abuse and presented with major upper GIB requiring a median of 8 units (range 2 – 40) blood, transfusion. Nine had upper abdominal pain at the time of admission and nine had a history of pancreatitis. Upper gastroduodenal endoscopy (median 4; range 1 – 9), was diagnostic in only one. Side-viewing endoscopy showed bleeding from the pancreatic duct in 7 of 8 patients. Visceral aneurysms were demonstrated in 7 of 9 patients in whom coeliac angiography was carried out: (splenic artery 4, gastroduodenal artery 2, and pancreaticoduodenal artery 1). Two of 4 selective embolisations were successful. Six patients underwent distal pancreatectomy, 1 had gastroduodenal artery ligation and 1 died of coagulopathy following a total pancreatectomy. Pancreatic duct haemorrhage should be considered in patients with unexplained recurrent upper GIB, alcohol abuse and epigastric pain, particularly in those with established chronic pancreatitis. Selective angiography is essential for diagnosis and management. For bleeding sites in the head of the pancreas, embolisation should be attempted to avoid major resection. Distal pancreatectomy is preferred for splenic artery lesions.

Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product

Aspirin products are known to cause irritation and injury to the gastric mucosa. The belief that enteric-coated and buffered varieties are less likely to occasion major upper-gastrointestinal bleeding (UGIB) than plain aspirin was tested in data from a multicentre case-control study. 550 incident cases of UGIB admitted to hospital with melaena or haematemesis and confirmed by endoscopy, and 1202 controls identified from population census lists, were interviewed about use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) during the 7 days before the onset of bleeding (cases) or interview (controls). Relative risks of UGIB for each type of aspirin used regularly (at least every other day) were calculated overall, and according to dose, by multiple logistic regression, with control for age, sex, marital status, date, education, cigarette smoking, alcohol use, and use of NSAIDs. The relative risks of UGIB for plain, enteric-coated, and buffered aspirin at average daily doses of 325 mg or less were 2.6, 2.7, and 3.1, respectively. At doses greater than 325 mg, the relative risk was 5.8 for plain and 7.0 for buffered aspirin; there were insufficient data to evaluate enteric-coated aspirin at this dose level. There were no important differences in risk attributable to the three aspirin forms according to bleeding site (gastric vs duodenal), or when users of NSAIDs were excluded. Use of low doses of enteric-coated or buffered aspirin carries a three-fold increase in the risk of major UGIB. The assumption that these formulations are less harmful than plain aspirin may be mistaken.

Accuracy of diagnostic procedures in acute upper gastrointestinal bleeding

Aspirin products are known to cause irritation and injury to the gastric mucosa. The belief that enteric-coated and buffered varieties are less likely to occasion major upper-gastrointestinal bleeding (UGIB) than plain aspirin was tested in data from a multicentre case-control study.550 incident cases of UGIB admitted to hospital with melaena or haematemesis and confirmed by endoscopy, and 1202 controls identified from population census lists, were interviewed about use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) during the 7 days before the onset of bleeding (cases) or interview (controls). Relative risks of UGIB for each type of aspirin used regularly (at least every other day) were calculated overall, and according to dose, by multiple logistic regression, with control for age, sex, marital status, date, education, cigarette smoking, alcohol use, and use of NSAIDs.The relative risks of UGIB for plain, enteric-coated, and buffered aspirin at average daily doses of 325 mg or less were 2·6, 2·7, and 3·1, respectively. At doses greater than 325 mg, the relative risk was 5·8 for plain and 7·0 for buffered aspirin; there were insufficient data to evaluate enteric-coated aspirin at this dose level. There were no important differences in risk attributable to the three aspirin forms according to bleeding site (gastric vs duodenal), or when users of NSAIDs were excluded.Use of low doses of enteric-coated or buffered aspirin carries a three-fold increase in the risk of major UGIB. The assumption that these formulations are less harmful than plain aspirin may be mistaken.

Prevention of upper gastrointestinal bleeding in long-term ventilated patients: Sucralfate versus ranitidine

Thirty-two long-term ventilated patients were randomly selected for a study of the efficacy of sucralfate (1 g six times per day via gastric tube) versus ranitidine (six 50-mg to six 100-mg doses per day intravenously) for the prevention of upper gastrointestinal bleeding. The patients of the two treatment groups (each 16) were comparable with respect to diseases precipitating acute respiratory failure and risk factors of bleeding, e.g., renal failure, thrombopenia, coagulopathy, and anticoagulant treatment. Mean duration of mechanical ventilation was 7.4 in sucralfate- and 7.7 days in ranitidine-treated patients. During mechanical ventilation, macroscopically visible bleeding developed in three of the sucralfate-treated (18.7 percent) and seven of the ranitidine-treated (43.7 percent) patients. Until the end of the study, only three of the sucralfate-treated but nine of the ranitidine-treated (56.2 percent) patients bled; the difference between the two treatment groups was at all times significant (p <0.05). Packed red blood cells had to be administered to the three bleeding patients in the sucralfate group and to seven bleeding in the ranitidine group. Therefore it seems that sucralfate prevented mostly minor bleeding. The high bleeding rate during ranitidine treatment was presumably due to the high number of pH-nonresponders, as almost 30 percent of the gastric aspirates of this group had a pH less than 5. During treatment no difference was found in positive blood culture specimens and bronchial secretions between the two groups. However, nosocomial pneumonia developed in two ranitidine-treated patients, whereas that complication developed in none of the sucralfate-treated patients. In long-term ventilated patients, sucralfate prevented minor upper gastrointestinal bleeding significantly better than ranitidine. However, this does not imply that major upper gastrointestinal bleeding can be prevented by either sucralfate or ranitidine in these patients.

Prevention of upper gastrointestinal bleeding in burn patients: a role for 'elemental' diet.

In a retrospective study, the role of the elemental diet in preventing upper gastrointestinal (GI) bleeding was evaluated in 146 severely burned patients. The patients were divided into two groups. Group A consisted of 77 patients with 20% to 80% body-surface-area burns who received the usual diet. Group B consisted of 69 patients with similar-sized burns receiving Vivonex as the elemental diet. In group A, the incidence of upper GI bleeding was 44%, major upper GI bleeding was 30%, and two patients required surgery. The incidence of upper GI bleeding in group B was 20%, major upper GI bleeding was 3%, and no patients required surgery. Group A had 55% mortality, and group B, 38% mortality. Vivonex was associated with a noticeable decrease in major upper GI bleeding in severely burned patients, and unlike antacid and cimetidine therapy, contributed concomitantly to increased caloric intake.

IMPACT OF CHANGE TO EARLY DIAGNOSIS AND SURGERY IN MAJOR UPPER GASTROINTESTINAL BLEEDING

The diagnostic, operation, and mortality rates in two series of patients with major upper gastrointestinal bleeding have been compared. In one (1968-69) patients were admitted to medical wards, radiology was the only investigation, and few were operated on. In 1972-74 a more vigorous policy was adopted with investigation by both radiology and endoscopy, more (and earlier) surgery, and intensive care by a surgical team. Failure to reach a diagnosis fell from 38·9% to 5·7%; the operation-rate increased; transfusion requirements decreased; and mortality in both operated (47% v. 11%) and non-operated (17% v. 8%) fell. A policy of early and vigorous investigation and management by a surgical team is urged for patients presenting with severe bleeding from the duodenum, stomach, or œsophagus.

Aspirin use in patients with major upper gastrointestinal bleeding and peptic-ulcer disease. A report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center.

Possible relations between long-term regular use of aspirin-containing drugs and hospital admissions for (1) major upper gastrointestinal bleeding in the absence of known predisposing conditions and (2) newly diagnosed peptic ulcer were explored in a large hospital survey. For patients who were admitted with major bleeding and in whom there was no evidence of duodenal ulcer, there was a statistically significant association with aspirin taken regularly for four or more days a week (p<0.01). A similar association was found for patients admitted with newly diagnosed and uncomplicated benign gastric ulcer (p<0.05). The corresponding estimated incidence rates of hospital admissions, for these two conditions, that were attributable to this level of aspirin use were 15 and 10 per 100,000 users per year, respectively. Aspirin taken regularly for four or more days a week was not significantly associated with either bleeding or uncomplicated duodenal ulcer. There was no evidence of significant associations with the diseases under consideration when less heavy use of aspirin was considered. (N Engl J Med 290:1158–1162, 1974)