MEDLINE Abstracts: PPIs in the Critical Care Setting
MEDLINE Abstracts: PPIs in the Critical Care Setting
What's new concerning the role of proton-pump inhibitors (PPIs) in the critical care setting? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Gastroenterology.
Spiegel BM, Ofman JJ, Woods K, Vakil NB
Am J Gastroenterol. 2003;98:86-97
Objectives: Controversy exists regarding the optimal strategy to minimize recurrent ulcer hemorrhage after successful endoscopic hemostasis. Our objective was to evaluate the cost-effectiveness of competing strategies for the posthemostasis management of patients with high risk ulcer stigmata.
Methods: Through decision analysis, we calculated the cost-effectiveness of four strategies: 1) follow patients clinically after hemostasis and repeat endoscopy only in patients with evidence of rebleeding (usual care); 2) administer intravenous proton pump inhibitors (i.v. PPIs) after hemostasis and repeat endoscopy only in patients with clinical signs of rebleeding; 3) perform second look endoscopy at 24 h in all patients with successful endoscopic hemostasis; and 4) perform selective second look endoscopy at 24 h only in patients at high risk for rebleeding as identified by the prospectively validated Baylor Bleeding Score. Probability estimates were derived from a systematic review of the medical literature. Cost estimates were based on Medicare reimbursement. Effectiveness was defined as the proportion of patients with rebleeding, surgery, or death prevented.
Results: The selective second look endoscopy strategy was the most effective and least expensive of the four competing strategies, and therefore dominated the analysis. The i.v. PPI strategy required 50% fewer endoscopies than the competing strategies, and became the dominant strategy when the rebleed rate with i.v. PPIs fell below 9% and when the cost of i.v. PPIs fell below 10 dollars/day.
Conclusions: Compared with the usual practice of "watchful waiting," performing selective second look endoscopy in high risk patients may prevent more cases of rebleeding, surgery, or death at a lower overall cost. However, i.v. PPIs are likely to reduce the need for second look endoscopy and may be preferred overall if the rebleed rate and cost of i.v. PPIs remains low.
Huggins RM, Scates AC, Latour JK
Ann Pharmacother. 2003;37:433-437
Objective: To evaluate the evidence supporting the use of intravenous proton-pump inhibitors in the treatment of gastrointestinal (GI) hemorrhage in comparison with histamine(2) (H(2))-receptor antagonists. DATA SOURCES: Clinical literature was accessed through a MEDLINE search (1966-October 2002). Data from abstracts and fully published articles were retrieved for analysis. Key search terms included pantoprazole, omeprazole, proton-pump inhibitors, gastrointestinal hemorrhage, histamine(2)-receptor antagonists, ranitidine, and cimetidine.
Data Synthesis: There are limited published clinical outcome data evaluating the use of intravenous pantoprazole in patients with upper GI hemorrhage. However, there are several gastric pH studies suggesting that intravenous pantoprazole is effective in quickly obtaining and maintaining a pH >6. When considering the results from studies of high-dose intravenous omeprazole, in addition to the pantoprazole data, the relative efficacy of intravenous proton-pump inhibitors appears to be superior to that of intravenous H(2)-receptor antagonists in providing a more predictable and sustained pH control.
Conclusions: Intravenous proton-pump inhibitors are suitable, possibly superior, alternatives to intravenous H(2)-receptor antagonists in treatment of upper GI bleeding.
Yang YX, Lewis JD
Semin Gastrointest Dis. 2003;14:11-19
Critically ill patients are at increased risk of developing stress-related mucosal lesions. The pathogenesis of stress-related mucosal disease is not entirely clear, but probably is associated with impairment of mucosal protective mechanisms due to compromised gastric mucosal microcirculation. Acid also plays an integral role. The incidence of gastrointestinal bleeding among intensive care unit patients has been declining over the past 30 years. Only a small proportion of patients with stress-related mucosal lesions develop clinically overt bleeding, and the majority of the overt bleedings do not lead to hemodynamic instability. However, the presence of gastrointestinal bleeding in a critically ill patient predicts markedly increased mortality. Prolonged mechanical ventilation and coagulopathy are the most important predictors of stress ulcer related bleeding. Critically ill patients with stress ulcer related bleeding should be managed in the acute setting just as patients presenting with upper gastrointestinal bleeding. Available evidence supports the use of stress ulcer prophylaxis in patients with risk factors for bleeding. Both histamine 2 receptor antagonists and sucralfate are effective forms of stress ulcer bleeding prophylaxis. More potent acid suppression by proton pump inhibitors may offer additional benefit in the prevention of stress ulcer bleeding.
Barkun AN
Drugs Today (Barc). 2003;39(suppl A):3-10
Upper gastrointestinal (GI) bleeding is a common cause of hospitalization and despite effective endoscopic treatments, it is responsible for a significant societal burden due to the associated morbidity, mortality and financial implications. As it has long been hypothesized that acid suppression may help to improve outcomes of patients with gastroduodenal ulcer bleeding, acid-suppressing agents such as histamine-2 receptor antagonists (H(2)RAs) and intravenous (i.v.) proton pump inhibitors (PPIs) have been the subject of study. However, results for H(2)RAs show little if any improvement in outcomes, which may be explained by their insufficient acid suppression and the existence of rapid drug tolerance. The advent of i.v. proton pump inhibition has made possible a more profound and sustained, predictable acid suppression without the development of tolerance to the drug. Recently published studies on the use of i.v. PPIs in over 1,500 patients have shown that they have an excellent safety profile. Cost-effectiveness decision models have also suggested, in a preliminary fashion, their cost- effectiveness for use following endoscopic hemostasis in patients with bleeding ulcers. The Canadian Registry of Patients with Upper Gastrointestinal Bleeding Undergoing Endoscopy (RUGBE) recorded information on patient characteristics, diagnosis and treatment from 1999-2002 and preliminary data indicate protective effects of endoscopic treatment and PPI use in specific patient subgroups. Randomized trials and meta-analyses have shown that acute high-dose i.v. PPI administration leads to improvements in patients undergoing endoscopic hemostasis for bleeding gastroduodenal ulcers and who also show high risk for rebleeding. However, the optimum dose, timing of administration and subgroups of patients who will benefit most from such treatment need to be further characterized.
Enns RA, Gagnon YM, Rioux KP, Levy AR
Aliment Pharmacol Ther. 2003;17:225-233
Background: The administration of proton pump inhibitors intravenously after endoscopic treatment of peptic ulcers significantly reduces the recurrence of bleeding. AIM: To evaluate the incremental cost-effectiveness in Canada of intravenous proton pump inhibitor before endoscopic therapy to patients presenting with acute upper gastrointestinal bleeding, compared with endoscopic treatment alone.
Methods: From a third-party payer perspective, we modelled the costs and effectiveness over 60 days of the two approaches using decision analysis. The probabilities of various outcomes, such as re-bleeding and the need for surgery, were taken from the published literature. We included the costs of intravenous proton pump inhibitor, therapeutic endoscopy, surgical procedures and hospitalizations, all expressed in 2001 Canadian dollars.
Results: In a hypothetical cohort of 1000 patients, the intravenous proton pump inhibitor approach resulted in mean savings of 20,700 Canadian dollars with 37 re-bleeding episodes averted. The investigation of uncertainty resulted in a likelihood of intravenous proton pump inhibitor being cost-effective of at least 0.73.
Conclusion: It is common in Canada to administer intravenous proton pump inhibitors to patients with upper gastrointestinal bleeding even before endoscopic confirmation of bleeding peptic ulcers. Our results suggest that this approach has a high likelihood of being cost-effective.
Cash BD
Crit Care Med. 2002;30:S373-S378
An evidence-based-medicine approach may be applied to studies in the medical literature to help physicians make sound judgments about efficacy and safety data and to improve clinical decision making. To assess the role of gastric acid suppression in the prevention of stress ulcer bleeding and in the management of upper gastrointestinal bleeding after successful hemostasis of bleeding peptic ulcer disease, the following questions should be addressed: Is it possible to identify risk factors for clinically important bleeding in critically ill patients? Can intravenous acid suppression prevent stress ulcer-related bleeding or prevent rebleeding in peptic ulcers after successful hemostasis? What is the most effective method of acid suppression for these disorders? An evidence-based-medicine review of published trials yields sufficient evidence to support the use of prophylactic acid suppression in critically ill patients with coagulopathy or in those who are receiving prolonged mechanical ventilation. Not enough data have accumulated to prove the superiority of intravenous proton pump inhibitors to intravenous histamine-2-receptor antagonists for prophylaxis of clinically important stress ulcer bleeding. With respect to acute gastrointestinal bleeding, however, two well-conducted trials indicate that an intravenous proton pump inhibitor is significantly more effective than an intravenous histamine-2-receptor antagonist or placebo in reducing the rate of rebleeding after hemostasis in patients with bleeding peptic ulcer. Analysis of the data from both trials shows that only five to six patients would need to receive an intravenous proton pump inhibitor to avoid one episode of rebleeding.
Morgan D
Crit Care Med. 2002;30:S369-S372
Two well-controlled trials were carried out to investigate the effectiveness of intravenous proton pump inhibitors (PPIs) to reduce peptic ulcer rebleeding after successful hemostasis. The results demonstrated that the PPI reduced the rate of rebleeding significantly. The recent availability of the first intravenous PPI formulation in the United States, intravenous pantoprazole, represents an alternative to intravenous histamine-2 receptor antagonists. The results of 16 randomized, controlled trials involving a total of >3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest that bolus administration plus continuous infusion of PPIs is a more effective pharmacotherapy than bolus infusion alone in decreasing both rebleeding and the need for surgery. Optimal effect is achieved with an intravenous 80-mg bolus, followed by continuous infusion of 8 mg/hr for 3 days, after which therapy may be continued with an oral PPI. Intermittent bolus administration yielded a minimal benefit. A difference in mortality rates has not yet been demonstrated.
What's new concerning the role of proton-pump inhibitors (PPIs) in the critical care setting? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Gastroenterology.
Spiegel BM, Ofman JJ, Woods K, Vakil NB
Am J Gastroenterol. 2003;98:86-97
Objectives: Controversy exists regarding the optimal strategy to minimize recurrent ulcer hemorrhage after successful endoscopic hemostasis. Our objective was to evaluate the cost-effectiveness of competing strategies for the posthemostasis management of patients with high risk ulcer stigmata.
Methods: Through decision analysis, we calculated the cost-effectiveness of four strategies: 1) follow patients clinically after hemostasis and repeat endoscopy only in patients with evidence of rebleeding (usual care); 2) administer intravenous proton pump inhibitors (i.v. PPIs) after hemostasis and repeat endoscopy only in patients with clinical signs of rebleeding; 3) perform second look endoscopy at 24 h in all patients with successful endoscopic hemostasis; and 4) perform selective second look endoscopy at 24 h only in patients at high risk for rebleeding as identified by the prospectively validated Baylor Bleeding Score. Probability estimates were derived from a systematic review of the medical literature. Cost estimates were based on Medicare reimbursement. Effectiveness was defined as the proportion of patients with rebleeding, surgery, or death prevented.
Results: The selective second look endoscopy strategy was the most effective and least expensive of the four competing strategies, and therefore dominated the analysis. The i.v. PPI strategy required 50% fewer endoscopies than the competing strategies, and became the dominant strategy when the rebleed rate with i.v. PPIs fell below 9% and when the cost of i.v. PPIs fell below 10 dollars/day.
Conclusions: Compared with the usual practice of "watchful waiting," performing selective second look endoscopy in high risk patients may prevent more cases of rebleeding, surgery, or death at a lower overall cost. However, i.v. PPIs are likely to reduce the need for second look endoscopy and may be preferred overall if the rebleed rate and cost of i.v. PPIs remains low.
Huggins RM, Scates AC, Latour JK
Ann Pharmacother. 2003;37:433-437
Objective: To evaluate the evidence supporting the use of intravenous proton-pump inhibitors in the treatment of gastrointestinal (GI) hemorrhage in comparison with histamine(2) (H(2))-receptor antagonists. DATA SOURCES: Clinical literature was accessed through a MEDLINE search (1966-October 2002). Data from abstracts and fully published articles were retrieved for analysis. Key search terms included pantoprazole, omeprazole, proton-pump inhibitors, gastrointestinal hemorrhage, histamine(2)-receptor antagonists, ranitidine, and cimetidine.
Data Synthesis: There are limited published clinical outcome data evaluating the use of intravenous pantoprazole in patients with upper GI hemorrhage. However, there are several gastric pH studies suggesting that intravenous pantoprazole is effective in quickly obtaining and maintaining a pH >6. When considering the results from studies of high-dose intravenous omeprazole, in addition to the pantoprazole data, the relative efficacy of intravenous proton-pump inhibitors appears to be superior to that of intravenous H(2)-receptor antagonists in providing a more predictable and sustained pH control.
Conclusions: Intravenous proton-pump inhibitors are suitable, possibly superior, alternatives to intravenous H(2)-receptor antagonists in treatment of upper GI bleeding.
Yang YX, Lewis JD
Semin Gastrointest Dis. 2003;14:11-19
Critically ill patients are at increased risk of developing stress-related mucosal lesions. The pathogenesis of stress-related mucosal disease is not entirely clear, but probably is associated with impairment of mucosal protective mechanisms due to compromised gastric mucosal microcirculation. Acid also plays an integral role. The incidence of gastrointestinal bleeding among intensive care unit patients has been declining over the past 30 years. Only a small proportion of patients with stress-related mucosal lesions develop clinically overt bleeding, and the majority of the overt bleedings do not lead to hemodynamic instability. However, the presence of gastrointestinal bleeding in a critically ill patient predicts markedly increased mortality. Prolonged mechanical ventilation and coagulopathy are the most important predictors of stress ulcer related bleeding. Critically ill patients with stress ulcer related bleeding should be managed in the acute setting just as patients presenting with upper gastrointestinal bleeding. Available evidence supports the use of stress ulcer prophylaxis in patients with risk factors for bleeding. Both histamine 2 receptor antagonists and sucralfate are effective forms of stress ulcer bleeding prophylaxis. More potent acid suppression by proton pump inhibitors may offer additional benefit in the prevention of stress ulcer bleeding.
Barkun AN
Drugs Today (Barc). 2003;39(suppl A):3-10
Upper gastrointestinal (GI) bleeding is a common cause of hospitalization and despite effective endoscopic treatments, it is responsible for a significant societal burden due to the associated morbidity, mortality and financial implications. As it has long been hypothesized that acid suppression may help to improve outcomes of patients with gastroduodenal ulcer bleeding, acid-suppressing agents such as histamine-2 receptor antagonists (H(2)RAs) and intravenous (i.v.) proton pump inhibitors (PPIs) have been the subject of study. However, results for H(2)RAs show little if any improvement in outcomes, which may be explained by their insufficient acid suppression and the existence of rapid drug tolerance. The advent of i.v. proton pump inhibition has made possible a more profound and sustained, predictable acid suppression without the development of tolerance to the drug. Recently published studies on the use of i.v. PPIs in over 1,500 patients have shown that they have an excellent safety profile. Cost-effectiveness decision models have also suggested, in a preliminary fashion, their cost- effectiveness for use following endoscopic hemostasis in patients with bleeding ulcers. The Canadian Registry of Patients with Upper Gastrointestinal Bleeding Undergoing Endoscopy (RUGBE) recorded information on patient characteristics, diagnosis and treatment from 1999-2002 and preliminary data indicate protective effects of endoscopic treatment and PPI use in specific patient subgroups. Randomized trials and meta-analyses have shown that acute high-dose i.v. PPI administration leads to improvements in patients undergoing endoscopic hemostasis for bleeding gastroduodenal ulcers and who also show high risk for rebleeding. However, the optimum dose, timing of administration and subgroups of patients who will benefit most from such treatment need to be further characterized.
Enns RA, Gagnon YM, Rioux KP, Levy AR
Aliment Pharmacol Ther. 2003;17:225-233
Background: The administration of proton pump inhibitors intravenously after endoscopic treatment of peptic ulcers significantly reduces the recurrence of bleeding. AIM: To evaluate the incremental cost-effectiveness in Canada of intravenous proton pump inhibitor before endoscopic therapy to patients presenting with acute upper gastrointestinal bleeding, compared with endoscopic treatment alone.
Methods: From a third-party payer perspective, we modelled the costs and effectiveness over 60 days of the two approaches using decision analysis. The probabilities of various outcomes, such as re-bleeding and the need for surgery, were taken from the published literature. We included the costs of intravenous proton pump inhibitor, therapeutic endoscopy, surgical procedures and hospitalizations, all expressed in 2001 Canadian dollars.
Results: In a hypothetical cohort of 1000 patients, the intravenous proton pump inhibitor approach resulted in mean savings of 20,700 Canadian dollars with 37 re-bleeding episodes averted. The investigation of uncertainty resulted in a likelihood of intravenous proton pump inhibitor being cost-effective of at least 0.73.
Conclusion: It is common in Canada to administer intravenous proton pump inhibitors to patients with upper gastrointestinal bleeding even before endoscopic confirmation of bleeding peptic ulcers. Our results suggest that this approach has a high likelihood of being cost-effective.
Cash BD
Crit Care Med. 2002;30:S373-S378
An evidence-based-medicine approach may be applied to studies in the medical literature to help physicians make sound judgments about efficacy and safety data and to improve clinical decision making. To assess the role of gastric acid suppression in the prevention of stress ulcer bleeding and in the management of upper gastrointestinal bleeding after successful hemostasis of bleeding peptic ulcer disease, the following questions should be addressed: Is it possible to identify risk factors for clinically important bleeding in critically ill patients? Can intravenous acid suppression prevent stress ulcer-related bleeding or prevent rebleeding in peptic ulcers after successful hemostasis? What is the most effective method of acid suppression for these disorders? An evidence-based-medicine review of published trials yields sufficient evidence to support the use of prophylactic acid suppression in critically ill patients with coagulopathy or in those who are receiving prolonged mechanical ventilation. Not enough data have accumulated to prove the superiority of intravenous proton pump inhibitors to intravenous histamine-2-receptor antagonists for prophylaxis of clinically important stress ulcer bleeding. With respect to acute gastrointestinal bleeding, however, two well-conducted trials indicate that an intravenous proton pump inhibitor is significantly more effective than an intravenous histamine-2-receptor antagonist or placebo in reducing the rate of rebleeding after hemostasis in patients with bleeding peptic ulcer. Analysis of the data from both trials shows that only five to six patients would need to receive an intravenous proton pump inhibitor to avoid one episode of rebleeding.
Morgan D
Crit Care Med. 2002;30:S369-S372
Two well-controlled trials were carried out to investigate the effectiveness of intravenous proton pump inhibitors (PPIs) to reduce peptic ulcer rebleeding after successful hemostasis. The results demonstrated that the PPI reduced the rate of rebleeding significantly. The recent availability of the first intravenous PPI formulation in the United States, intravenous pantoprazole, represents an alternative to intravenous histamine-2 receptor antagonists. The results of 16 randomized, controlled trials involving a total of >3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest that bolus administration plus continuous infusion of PPIs is a more effective pharmacotherapy than bolus infusion alone in decreasing both rebleeding and the need for surgery. Optimal effect is achieved with an intravenous 80-mg bolus, followed by continuous infusion of 8 mg/hr for 3 days, after which therapy may be continued with an oral PPI. Intermittent bolus administration yielded a minimal benefit. A difference in mortality rates has not yet been demonstrated.
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