Introduction Of H2-receptor Antagonists Research Articles

Factors affecting morbidity and mortality in peptic ulcer perforation

Background: Peptic ulcer disease is very common disease in developing countries and so are its complications. With the introduction of H2 receptor antagonists and proton pump inhibitors, the incidence of elective surgery for peptic ulcer (PU) disease has decreased dramatically, although complications of peptic ulcer disease such as perforation and bleeding have remained fairly constant.Methods: A prospective study was conducted on43 patients presenting to KIMS Hospital, Hubli with features suggestive of hollow viscus perforation and intraoperative findings suggestive of peptic ulcer perforation from January 2015 to June 2016.Results: In this study, there were 43 cases of peptic ulcer perforation. Peptic ulcer perforation was common in third decade of life(n=12) with the mean age(SD) 39.88 years. Perforation is more common in males as compared to the female population 7.6:1. Post-operative morbidity is seen in 31 (72.1%) of patients and mortality in 4 (9.3%). Smoking, Alcohol beverage consumption, regular ingestion of NSAIDs were commonly seen in patients with peptic ulcer perforation but these factors were not significant risk factors for postoperative mortality and morbidity. Age ≥60 years (p-value 0.051), Female gender (p-value 0.012), Presence of co-morbid conditions (p-value 0.055), Shock on admission (p-value 0.029, perforation-surgery interval >24 hours (p-value 0.001), preoperative higher-grade ASA, purulent intraperitoneal collection (p-value 0.002) were statistically significant predictors of mortality.Conclusions: Perforated peptic ulcer (PPU) is a life-threatening disease with historically reported high morbidity and mortality rates. Age ≥60 years, female gender, presence of co-morbidities, preoperative shock, higher ASA grade, perforation-surgery interval >24 hours, Purulent intraperitoneal collection are inter-related statistically significant predictors of mortality. Therefore, proper resuscitation from shock, improving ASA grade and decreasing delay in surgery is needed to improve overall results.

The scars of time: the disappearance of surgery for pyloric stenosis

IntroductionThe changing pattern of both elective and emergency operations for peptic ulcer disease (PUD) has been well described but less is known about operations for pyloric stenosis (PS).MethodsData registration was...

Factors affecting mortality and morbidity in patients with peptic ulcer perforation

With the introduction of H2 receptor antagonists and proton pump inhibitors, the incidence of elective surgery for peptic ulcer (PU) diseases has decreased, although complications of PU such as perforation and bleeding have remained fairly constant. The purpose of this study was to identify the risk factors that predict morbidity and mortality in patients with perforated PU. The records of 269 patients who were operated on for perforated PU were reviewed retrospectively. The following factors were analyzed in terms of morbidity and mortality: age >65 years; gender; associated medical illness; chronic ingestion of non-steroidal anti-inflammatory drugs, aspirin, corticosteroids or immunosuppressants; alcohol ingestion and smoking habits; American Society of Anesthesiologist (ASA) status; season; delayed operation; site of ulcer perforation; and shock on admission and type of operation. There were 30 female (11.16%) and 239 male (88.84%) patients. Seventy-one (26.4%) patients had associated diseases. Simple closure was performed in 257 (95.5%) patients; 12 patients (4.5%) underwent definitive operations. A total of 108 postoperative complications were present in 65 (24.2%) patients. Twenty-three patients died (8.55%). Multivariate analysis showed that only age, ASA score, treatment delay, presence of shock and definitive operation were independent predictors of mortality. Significant risk factors that led to morbidity were ASA status, time of surgery, season, presence of shock and type of surgery. There was a significant difference concerning morbidity and mortality between simple closure of the perforation and definitive surgery. Age, delayed surgery, presence of shock, ASA risk and definitive surgery are factors significantly associated with fatal outcomes in patients undergoing emergency surgery for perforated PU. Therefore, proper resuscitation from shock, improving ASA grade, decreasing delay and reserving definitive surgery for selected patients is needed to improve overall results.

Peptic ulcer surgery during the H2-receptor antagonist era: a population-based epidemiological study of ulcer surgery in Helsinki from 1972 to 1987.

To evaluate the effects of improvements in medical therapy on the incidence of, indications for and operative methods used in peptic ulcer surgery, all cases of primary peptic ulcer surgery among adults in the city of Helsinki in the years 1972, 1977, 1982 and 1987 were analysed. There was a total of 565 such cases in a population which consisted of 5.2 X 10(5) individuals in 1972 and 4.8 X 10(5) individuals in 1987. The introduction of H2-receptor antagonists in 1979 was associated with a fall in the annual incidence of elective duodenal ulcer operations, from 15.5 to 6.7 per 10(5) individuals, and a fall in the annual incidence of elective gastric ulcer operations, from 9.4 to 3.1 per 10(5) individuals (P less than 0.05). The decrease was greatest among males with duodenal ulcer. In contrast, the annual incidence of emergency surgery for ulcer haemorrhage and perforation (all types of ulcers) remained relatively stable, varying from 7.2 to 10.2 per 10(5) inhabitants over the observation period (n.s.). The mean age of patients undergoing elective surgery remained essentially unchanged. The mean age of patients undergoing emergency surgery increased. The decrease in the annual incidence of elective duodenal ulcer surgery occurred mainly in relation to proximal gastric vagotomy. There was a concomitant relative increase in the incidence of gastric resection. The types of operative procedures used in cases of pyloric, prepyloric and gastric ulcer remained unchanged over the years 1972 to 1987.

Changes in surgical strategies for peptic ulcers before and after the introduction of H2-receptor antagonists and endoscopic hemostasis.

A total of 902 surgical patients with peptic ulcer disease were evaluated to clarify the effects of H2-receptor antagonists and endoscopic hemostasis on surgical treatment. Following the introduction of these treatments to our institute in 1982, the number of operations performed annually decreased by 40%, or 36 cases per year. However, a remarkable increase in the frequency of surgical emergency intervention since 1982 was concurrently observed, with the ratio of emergency procedures to the total number of operated cases increasing to 72.5% in the last 5 years of the study. Moreover, intractability as an indication for surgery decreased to 34.1%, compared with an increase in the number of patients with bleeding and perforated ulcers requiring operation. There were 13 postoperative deaths recorded (1.4%). All of the deaths were in patients who had undergone emergency surgery in poor health. Of these 13 patients, 10 had bleeding ulcers. A study of bleeding ulcers for which endoscopic hemostasis had been unsuccessful revealed that shock on admission and a concomitant medical condition had been evident in all the patients who died, and in 52.2% and 30.4% of the survivors, respectively. The current study suggests that the frequency of high-risk patients requiring surgery is increasing since the introduction of H2-receptor antagonists and endoscopic hemostasis, and thus, prompt surgical treatment and intensive management for such patients is essential.

Recent trends in mortality from peptic ulcer disease in Finland.

The enormous change of medical therapy of peptic ulcer disease in the 1970s has resulted in a significant decrease of elective ulcer surgery. It has been speculated whether this might be reflected in the mortality of the disease. Therefore, in the present study, the mortality rate of the disease was evaluated in Finland during the past 17 years covering the dramatic change in the medical therapy: the introduction of H2-receptor antagonists. This was done with a population-based epidemiological study by analyzing 1262 death certificates of people dying from peptic ulcer disease in Finland between 1972 and 1989. The study showed that there has been almost twofold increase in the mortality of the disease between 1972 and 1989 in Finland. This was mainly due to the significantly increased number of fatal ulcer hemorrhages in older people, but also mortality from ulcer perforations increased. This unfavorable epidemiological progress was most striking among elderly women and became manifest during the 1980s. We conclude that mortality from peptic ulcer disease has significantly increased in Finland due to fatal ulcer hemorrhages and perforations. This epidemiological change became manifest in the 1980s, concurrently with the dramatic change in the medical therapy of peptic ulcer disease.

Economic evaluation of new medical technology.

Safety and efficacy are not the only parameters of interest for choice of medical technology--costs play an increasingly important role. There is a growing interest in 'value for money', which can be assessed by economic evaluation comparing the costs and consequences of alternative courses of action. A number of different economic evaluation methods may be used: cost-minimization (looking only at costs with no consideration of consequences); cost-effectiveness (in which a unidimensional clinical outcome is assessed, for example, life-years gained); cost-utility (measuring multidimensional outcomes, for example quantity and quality of life); and cost-benefit (where outcome is considered in monetary terms). A Swedish cost-of-illness study showed that the direct health care costs increased and the indirect cost (in terms of production loss) associated with treatment of peptic ulcer fell following the introduction of H2-receptor antagonists. In a study of reflux oesophagitis, omeprazole was shown to be more cost-effective than ranitidine. With omeprazole, the costs were lower and the effectiveness better than with the H2-receptor antagonist.

Session 6: Is Hypergastrinaemia Dangerous to Man?

Achlorhydria has been discussed as a possibly dangerous consequence of therapeutic inhibition of gastric acid secretion since the introduction of H2-receptor antagonists. The risk of long-term hypergastrinaemia has only been considered for about 5 years. The reason for this was the demonstration that gastric carcinoids (ECLomas) observed after life-long treatment of rats with the proton pump inhibitor omeprazole could also be produced in rats by other methods leading to long-lasting profound hypergastrinaemia. Such methods were the 80% resection of the oxyntic mucosa or feeding of ranitidine (2000 mg/day) for 2 years. The endocrine tumours corresponded to the gastric carcinoids found in patients with long-lasting hypergastrinaemia due to pernicious anaemia or with a gastrinoma as part of the MEN I syndrome. Neither in animals nor in man could other endocrine tumours or adenocarcinomas of the gastrointestinal tract be related to hypergastrinaemia. Epidemiologic data do not support gastrin dependence of adenocarcinoma of the stomach or the colon. Experimental findings of gastrin effects on tumour growth in vivo and in vitro have been contradictory and may be explained by the presence of gastrin receptors on tumour cells and the role of gastrin as an autocrine growth factor in some of these tumours. Since acid blockade by proton pump inhibitors or H2-receptor blockers dose-dependently increase serum gastrin levels, patients with ranitidine-resistant peptic ulceration receiving long-term treatment with high-dose omeprazole have been followed up with serial gastric biopsy specimens for up to 5 years. Complete healing, moderate hypergastrinaemia, and a slight hyperplasia but no dysplasia of the ECL cells in the oxyntic mucosa have been observed, which seemed to be correlated to chronic gastritis progressing over the years. Despite these negative findings excessive hypergastrinaemia by overdosage of potent drugs for inhibition of gastric secretion should be avoided and monitoring of plasma gastrin levels is recommended in case of long-term treatment.

All perforated ulcers are not alike.

To determine if ulcer location and other clinical factors affect the hospital course and early outcome of patients with perforated peptic ulcers in the decade since the introduction of H2 receptor antagonists, the records of 80 patients with perforated peptic ulcers were analyzed. Demographic factors, clinical features, and the outcome of patients with duodenal ulcer perforation were similar to patients with prepyloric ulcer perforation. In contrast, patients with gastric ulcer perforation had differing characteristics from the group with perforated pyloroduodenal ulcers. Overall, NSAID use preceded perforation in one half of the patients; severe coexisting medical illness and a short interval of symptoms before perforation were seen in more than one half of patients. Gastric ulcer location, hemodynamic instability, greater degree of peritoneal contamination, and larger ulcer size were factors associated with increased rates of mortality. Overall mortality rate was 12.5% and rate of morbidity was 33%. Oversewing with or without omental patch was the operation most commonly employed by a diverse group of surgeons.

What is new in the epidemiology and pathogenesis of peptic ulcer?

The old dictum 'no acid--no ulcer' is no longer a sufficient explanation of the pathogenesis of ulcer disease. The real question is 'if acid--why ulcer?' Although acid remains predominant, some of the other factors influencing ulcerogenesis are nocturnal acid secretion, pepsin enzyme subspecies, the mucus layer, bicarbonate levels, prostaglandins, Campylobacter pylori infection, consumption of non-steroidal anti-inflammatory drugs, and smoking habits. Although the ulcer burden has been greatly reduced by the introduction of H2-receptor antagonists, complications such as bleeding and perforation remain a problem, especially in the elderly. Medical treatment, in the form of H2-receptor antagonists, is effective for many patients.

Clinical Benefits of Intravenously Administered Famotidine in the Treatment of Upper Gastrointestinal Hemorrhage Caused by Peptic Ulcer and Stress Ulcer Disease

Bleeding may stop spontaneously in mild or moderate cases of GI bleeding. Therefore, to prove that H2-receptor antagonists effectively stop GI bleeding, evaluation of the results of treatment in patients who are classified as severe cases by the Nagao taxonomy is needed. Data from the literature show that mortality is higher in patients with specific endoscopic findings, such as active bleeding, visible vessels, clot, or stain, than it is in patients without these findings. The criteria for establishing whether H2-receptor antagonists effectively control GI bleeding in severe cases include a reduction in mortality, in the rate of recurrent bleeding, or in the rate of emergency surgery. Data gathered from a current multicenter trial assessing the efficacy of 20 mg famotidine administered intravenously twice daily show that the rate of emergency surgery in patients with bleeding ulcer is 8.6%, which is substantially less than the 54.2% rate found in a retrospective review of patients treated before the introduction of H2-receptor antagonists. In addition, there were no deaths among famotidine-treated patients. Similarly, among patients with bleeding caused by stress ulcer, the percentage who were treated with famotidine and required emergency surgery was much less than that in the historical control group (15.8% versus 40.0%). Famotidine was effective in greater than or equal to 88% of patients with peptic ulcers and in 78.9% of patients with stress ulcers. Recurrent bleeding occurred more often in patients with exposed blood vessels. Intravenously administered famotidine is, therefore, effective for the control of GI bleeding caused by severe peptic ulcer and stress ulcer disease.