Frank L. Lanza

Guidelines for Prevention of NSAID-Related Ulcer Complications

Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind, placebo-controlled studies are preferable, but compassionate use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine. Only when data that will not withstand objective scrutiny are available is a recommendation identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject, without regard to specialty training or interests, and are intended to indicate the preferable, but not necessarily the only, acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. These guidelines were developed under the auspices of the American College of Gastroenterology by a committee of experts in the field, reviewed by its Practice Parameters Committee, and approved by the Board of Trustees. The recommendations of these guidelines are therefore considered valid at the time of production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at an established time and indicated at publication to assure continued validity. Owing to the volume of new data on the subject of non-steroidal anti-inflammatory drug (NSAID)-related injury to the upper gastrointestinal tract, i.e., the advent of cyclooxygenase (COX)-2 inhibitors, new data on interactions between these agents, as well as traditional NSAIDs, with aspirin and H. pylori, it was elected by the Committee to confine these guidelines to upper gastrointestinal (GI) injury and to leave post-duodenal injury as the subject of a separate guideline.

A Guideline for the Treatment and Prevention of NSAID-Induced Ulcers

Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind, placebo-controlled studies are preferable, but compassionate use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject without regard to specialty training or interests and are intended to indicate the preferable, but not necessarily the only, acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Each has been intensely reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision analysis. The recommendations of each guideline are therefore considered valid at the time of their production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at publication to assure continued validity. INTRODUCTION

Endoscopic Evaluation of the Effects of Aspirin, Buffered Aspirin, and Enteric-Coated Aspirin on Gastric and Duodenal Mucosa

THE damaging effect of aspirin on the gastric mucosa has been well documented by endoscopy1 2 3 4 5 6 and by studies of fecal blood loss.7 , 8 Because of the unquestioned value of aspirin in the th...

Effect of ranitidine gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs

The effect of ranitidine in preventing mucosal damage caused by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated for eight weeks in a prospective study of 144 patients requiring NSAIDs. Patients with normal endoscopic findings were randomly assigned to receive either ranitidine 150 mg twice daily or placebo for eight weeks, along with either ibuprofen, indomethacin, naproxen, sulindac, or piroxicam. Duodenal damage was significantly less in the ranitidine group compared with the placebo group by weeks 4 and 8 (P≤0.01). Duodenal ulcers did not develop in any patients on ranitidine (0/57) compared with 4/49 patients (8%) on placebo (P=0.02). No significant difference was found between treatment groups with respect to gastric damage; 6/60 (10%) in the ranitidine group compared with 6/50 (12%) in the placebo group developed gastric ulcers. These findings suggest that acid suppression is of greater importance for mucosal protection in the duodenum than in the stomach, where other defense mechanisms may be operative. While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage.

Seven‐day therapy for Helicobacter pylori in the United States

Background : The ideal duration of Helicobacter pylori treatment in the United States and whether eradication therapy is as successful in nonulcer dyspepsia as in peptic ulcer disease are controversial topics.

The effects of ibuprofen, indomethacin, aspirin, naproxen, and placebo on the gastric mucosa of normal volunteers: a gastroscopic and photographic study.

The effects of various nonsteroidal antiinflammatory drugs on the gastric mucosa were endoscopically evaluated in 40 normal volunteers. Eight groups, each containing five subjects were designed: aspirin (3600 mg/d); placebo; ibuprofen (1600 mg/d); ibuprofen (2400 mg/d); indomethacin (100 mg/d); indomethacin (150 mg/d); naproxen (500 mg/d); and naproxen (750 mg/d). All volunteers took medication for seven days and gastroscopy was carried out on day one and day eight. All findings were documented by photography. Severe gastric mucosal injury occurred with aspirin (P<0.05), both doses of indomethacin, and the higher dose of naproxen. Lesser changes were seen with the lower dose of naproxen, both doses of ibuprofen and placebo. The higher doses of ibuprofen, indomethacin, and naproxen caused a greater degree of gastric mucosal injury, but statistical significance was achieved only with naproxen (P<0.01). Subjective gastrointestinal complaints generally correlated with endoscopic pathology; however, nine volunteers had evidence of severe injury to the gastric mucosa with no symptomatology. This was confined to the patients on indomethacin, naproxen, and ibuprofen. Aspirin patients all had some degree of symptomatology but to a lesser degree than expected in view of the endoscopic findings.

Double-blind, placebo-controlled endoscopic comparison of the mucosal protective effects of misoprostol versus cimetidine on tolmetin-induced mucosal injury to the stomach and duodenum

Ninety normal volunteers were entered into a double-blind, placebo-controlled study to compare the efficacy of misoprostol (200 micrograms q.i.d.) vs. cimetidine (300 mg q.i.d.) in protecting the gastric and duodenal mucosa from tolmetin-induced (400 mg q.i.d.) injury. After 6 days of treatment, the degree of mucosal injury between treatments was compared by endoscopy, using a predetermined rating scale of 0 (normal mucosa) to 4+ (greater than 25 hemorrhages or erosions or an invasive ulcer). Utilizing a score of less than or equal to 2+ (2-10 hemorrhages or erosions) as a therapeutic success, the overall success rates were 8/30 (26.7%) for placebo, 19/30 (63.3%) for cimetidine, and 27/29 (93.1%) for misoprostol (p less than 0.001). Pairwise comparisons were also significant: misoprostol vs. placebo (p less than 0.001), misoprostol vs. cimetidine (p = 0.006), and cimetidine vs. placebo (p = 0.004). A separate analysis of the gastric scores alone revealed success rates identical to those in the overall evaluation; however, success rates in the duodenum for both misoprostol (29/29) and cimetidine (29/30) were extremely high and did not differ. It is concluded that misoprostol is highly effective and significantly better than cimetidine in protecting the gastric mucosa from tolmetin-induced injury; however, both agents were highly protective in the duodenum.

A double-blind study of prophylactic effect of misoprostol on lesions of gastric and duodenal mucosa induced by oral administration of tolmetin in healthy subjects

Tolmetin, a nonsteroidal antiinflammatory drug, is known to induce edema, submucosal hemorrhage, and erosions of the gastrointestinal tract when administered at recommended doses. The purpose of our study was to determine whether misoprostol prevented or reduced the severity of duodenal and gastric mucosal injury induced by tolmetin. Following endoscopic screening, 60 healthy male and female subjects were assigned at random to one of two treatment groups. One group was treated with tolmetin (2000 mg/day, in four divided doses) and misoprostol (200 μg four times daily); the other with tolmetin and placebo. Both drugs were administered for six and a quarter days. On the seventh day, 2 hr after the last dose, an endoscopic examination of the gastric and duodenal mucosa was repeated, and the results graded. Subjects with 10 or fewer hemorrhages or erosions were considered treatment successes; those with 11 or more erosions, plus any other lesions, were considered treatment failures. A total of 59 subjects completed the study. One withdrew because of an unsuspected pregnancy. In regard to the gastric mucosa, seven of 29 (24%) placebo subjects were considered treatment successes. In the misoprostol group, 27 of 30 (90%) were treatment successes. This difference is statistically significant at theP<0.0001 level. The overall damage to the duodenal mucosa caused by tolmetin is less than that to the gastric mucosa, with the misoprostol-treated subjects having significantly less damage than the placebo subjects (P<0.001). Side effects were common in both groups, but almost all were mild, gastrointestinal in origin, and did not require treatment or withdrawal from the study. In conclusion, misoprostol is effective in preventing gastric and duodenal mucosal injury induced by tolmetin and, perhaps, by other nonsteroidal antiinflammatory drugs as well.

Endoscopic comparison of cimetidine and sucralfate for prevention of naproxen-induced acute gastroduodenal injury

Nonsteroidal antiinflammatory drug-induced gastroduodenal mucosal damage observed endoscopically is usually categorized as hemorrhages, erosions, or ulcerations. We undertook this study to determine whether the injury produced by a commonly prescribed NSAID, naproxen, could be reduced by cotherapy with sucralfate or cimetidine and to determine how dependent the differences in the degree of protection against mucosal injury measured were on the scoring system used. Four groups of 20 healthy volunteers with endoscopically normal gastric and duodenal mucosa received naproxen (500 mg twice a day) plus cimetidine (300 mg four times a day or 400 mg twice a day), sucralfate (1 g four times a day), or placebo for seven days. After seven days of therapy, a second endoscopy was performed. Separate scoring systems were used for the presence of hemorrhages, erosions, and a combination of both types of injury. There were significantly fewer mucosal hemorrhages present when naproxen and cimetidine were administered than when naproxen was administered with placebo or sucralfate (placebo vs 300 mg cimetidine, P=0.04, and placebo vs 400 mg cimetidine, P=0.006, placebo vs sucralfate, P=0.26). Both cimetidine dosages resulted in significantly fewer hemorrhages than were present following cotherapy of naproxen and sucralfate (P<0.05). In contrast, there was no discernible difference in the mucosal injury between placebo and any drug or between any two active therapies when the injury was evaluated based on the presence of gastric erosions. Duodenal damage was infrequent and slight following naproxen administration; erosions were present in all drug treatment groups but were numerous in only 10% (two of 20) of naproxen-placebotreated subjects, and there was no significant difference between any two groups. The scoring system that used the combination of hemorrhages and erosions showed that the naproxen-placebo group had significantly more duodenal injury than either 400-mg cimetidine or sucralfate group (P<0.02, for each). We conclude that the coadministration of either H2-receptor antagonists or sucralfate fails to produce any clinically meaningful reduction in naproxen-induced acute gastroduodenal mucosal erosion or ulceration and that reliance on reductions in endoscopic damages scores either based on, or heavily influenced by, hemorrhages (or hemorrhages plus erythema) may provide misleading information to the clinician.

An assessment of the management of acute bleeding varices: a multicenter prospective member-based study

OBJECTIVE:Bleeding from esophagogastric varices is a major complication of portal hypertension. Despite recent practice guidelines for the management of bleeding esophageal or gastric varices, the widespread application of these measures by gastroenterologists has not been evaluated. The purpose of this study was to continue the concept of membership-based research within diverse practice settings by expanding the American College of Gastroenterology (ACG) GI Bleeding Registry to assess the management and outcome of acute variceal bleeding.METHODS:All ACG members (domestic and foreign) were invited to participate during the 1997 Annual Fall meeting and by mail. Data were collected over 12 months. Information obtained included physician training, practice demographics, patient demographics, disease etiology and severity, clinical presentation, medications, transfusion needs, therapy, complications, and rebleeding within 2 wk.RESULTS:A total of 93 physicians/centers (79.6% domestic, 26.9% university and affiliated, 3.2% Veterans Affairs) participated. Complete demographic data were available for 725 of the 741 patients enrolled with index bleeding. The median age of these 725 patients was 52 yr and 73.3% were male. The most common single etiology for portal hypertension was cirrhosis (94.3%). The most common causes of cirrhosis were alcohol (56.7%), hepatitis C virus (30.3%), and hepatitis B virus (10.0%). Hemodynamic instability was noted in 60.7% of the patients (22.3% tachycardic, 9.7% orthostatic, 28.7% hypotensive). Index interventions included banding (40.8%; median five bands), sclerotherapy (36.3%), combination banding/sclerotherapy (6.2%), octreotide (52.6%; median 3 days), balloon tamponade (5.5%), transjugular intrahepatic portosystemic shunt (TIPS) (6.6%), liver transplantation (1.1%), surgical shunt (0.7%), and embolization (0.1%). Transfusion of packed red blood cells, fresh frozen plasma, and platelets was given in 83.4%, 44.7%, and 24.6% of the patients with index bleeding, respectively. Median transfusion was four units of packed red blood cells, three units of fresh frozen plasma, and 1.5 units of platelets. Rebleeding occurred in 92 of the 741 patients (12.6%) at a median of 7 days (mean 11 days) and was treated by banding (18.5%; median six bands), sclerotherapy (30.4%), octreotide (63%; median 2 days), balloon tamponade (17.4%), TIPS (15.2%), and surgical shunt (3.3%). Complications from the index bleeding and rebleeding within 2 wk included ulceration (2.6%, 2.2%), aspiration (2.4%, 3.3%), medication side effects (0.8%, 0%), dysphagia (2.3%, 0%), odynophagia (2.2%,0%), encephalopathy (13%,17.4%), and hepatorenal syndrome (2.4%, 2.2%), respectively. After the index bleeding, 46.2% of patients were treated with β-blockers and 8.2% with nitrates. The majority of patients with index bleeding had Childs B cirrhosis (61.5%). Patients presenting with recurrent bleeding had mostly Childs B (46.7%) or Childs C cirrhosis (44.6%). The overall short-term mortality after index bleeding was 12.9%.CONCLUSIONS:Acute variceal hemorrhage occurs more often in patients with Childs B and C cirrhosis. Endoscopic banding is the most common single endoscopic intervention. Adjunctive pharmacotherapy is prevalent acutely and after stabilization. Both morbidity and mortality may be lower than reported in previous studies.