EBQ:Omeprazole in Bleeding Peptic Ulcers - Revision history

Ostermayer: Prepared the page for translation

2026-01-04T23:49:30Z

Prepared the page for translation

GregArmani: /* Study Design */

2015-10-10T00:35:07Z

Study Design

← Older revision		Revision as of 00:35, 10 October 2015
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	**Studied end points may not directly translate to the emergency department, as the composite outcomes do not require the patient to be clinically sick.		**Studied end points may not directly translate to the emergency department, as the composite outcomes do not require the patient to be clinically sick.
	===Study Design===		===Study Design===
	*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.		Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.
	**While this study showed a significant difference in an Asian population with this composite outcomes, studies performed in Western, industrialized countries have demonstrated decreased efficacy, and even increased mortality		*While this study showed a significant difference in an Asian population with this composite outcomes, studies performed in Western, industrialized countries have demonstrated decreased efficacy, and even increased mortality
	**Study completed in 1997 to study efficacy of PPI in western patients with peptic ulcers was stopped early due to statistically significant mortality in patients who received PPI <ref>Hasselgren G et al. (1997) Continuous intravenous infusion of omeprazole in elderly patients with peptic ulcer bleeding: results of a placebo-controlled multicenter study. Scand J Gastroenterol 32: 328-333</ref>		*Study completed in 1997 to study efficacy of PPI in western patients with peptic ulcers was stopped early due to statistically significant mortality in patients who received PPI <ref>Hasselgren G et al. (1997) Continuous intravenous infusion of omeprazole in elderly patients with peptic ulcer bleeding: results of a placebo-controlled multicenter study. Scand J Gastroenterol 32: 328-333</ref>
	*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>
	**Past studies have shown that interobsrver agreement in peptic ulcer classification is poor to fair <ref>Lau JY1, Sung JJ, Chan AC, Lai GW, Lau JT, Ng EK, Chung SC, Li AK. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc. 1997 Jul;46(1):33-6.</ref>		Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>
	*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring		*Past studies have shown that interobsrver agreement in peptic ulcer classification is poor to fair <ref>Lau JY1, Sung JJ, Chan AC, Lai GW, Lau JT, Ng EK, Chung SC, Li AK. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc. 1997 Jul;46(1):33-6.</ref>

			The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring

	===Further Discussion===		===Further Discussion===
	*Meta-analysis of PPI initiation prior to endoscopy in patients with upper GI bleeding showed no clinically significant difference between PPI vs. placebo. <ref>Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010, Issue 7.</ref>		*Meta-analysis of PPI initiation prior to endoscopy in patients with upper GI bleeding showed no clinically significant difference between PPI vs. placebo. <ref>Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010, Issue 7.</ref>

Ostermayer: /* Outcomes */

2015-09-30T14:27:35Z

Outcomes

← Older revision		Revision as of 14:27, 30 September 2015
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	*No significant difference in patients who underwent surgery (2.5% in [[omeprazole]] group vs. 7.5% in placebo group, P=0.14)		*No significant difference in patients who underwent surgery (2.5% in [[omeprazole]] group vs. 7.5% in placebo group, P=0.14)
	*No significant difference in patients who died within 30 days after endoscopy (4.2% in [[omeprazole]] group vs. 10% in placebo group, P=0.13)		*No significant difference in patients who died within 30 days after endoscopy (4.2% in [[omeprazole]] group vs. 10% in placebo group, P=0.13)


	~~===Subgroup analysis===~~


	==Criticisms & Further Discussion==		==Criticisms & Further Discussion==

Catierey: further discussion

2015-09-28T18:31:00Z

further discussion

← Older revision		Revision as of 18:31, 28 September 2015
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	===Study Design===		===Study Design===
	*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.		*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.
			**While this study showed a significant difference in an Asian population with this composite outcomes, studies performed in Western, industrialized countries have demonstrated decreased efficacy, and even increased mortality
			**Study completed in 1997 to study efficacy of PPI in western patients with peptic ulcers was stopped early due to statistically significant mortality in patients who received PPI <ref>Hasselgren G et al. (1997) Continuous intravenous infusion of omeprazole in elderly patients with peptic ulcer bleeding: results of a placebo-controlled multicenter study. Scand J Gastroenterol 32: 328-333</ref>
	*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>		*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>
	**Past studies have shown that interobsrver agreement in peptic ulcer classification is poor to fair <ref>Lau JY1, Sung JJ, Chan AC, Lai GW, Lau JT, Ng EK, Chung SC, Li AK. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc. 1997 Jul;46(1):33-6.</ref>		**Past studies have shown that interobsrver agreement in peptic ulcer classification is poor to fair <ref>Lau JY1, Sung JJ, Chan AC, Lai GW, Lau JT, Ng EK, Chung SC, Li AK. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc. 1997 Jul;46(1):33-6.</ref>
	*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring		*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring
	**Previous studies in white patients have shown high doses of [[omeprazole]] to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>
	**Although this study specifically demonstrated the use of [[omeprazole]] after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.
	===Further Discussion===		===Further Discussion===
	*Meta-analysis of PPI initiation prior to endoscopy in patients with upper GI bleeding showed no clinically significant difference between PPI vs. placebo. <ref>Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010, Issue 7.</ref>		*Meta-analysis of PPI initiation prior to endoscopy in patients with upper GI bleeding showed no clinically significant difference between PPI vs. placebo. <ref>Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010, Issue 7.</ref>
	**No significant difference in mortality, re-bleeding, or need for surgery		**No significant difference in mortality, re-bleeding, or need for surgery
	**Use of omeprazole likely less important before endoscopy		**Use of omeprazole likely less important before endoscopy, and may be harmful in Western, industialized countries

	==Funding==		==Funding==

Catierey: further discussion

2015-09-28T18:15:05Z

further discussion

← Older revision		Revision as of 18:15, 28 September 2015
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	**Hazard ratio: 3.9 (95% CI 1.7-9.0)		**Hazard ratio: 3.9 (95% CI 1.7-9.0)
	**Study stopped early due to significant difference between [[omeprazole]] and placebo (P<0.001)		**Study stopped early due to significant difference between [[omeprazole]] and placebo (P<0.001)
	*In vitro studies have shown that high intragastric pH ~~could~~ facilitate platelet aggregation, thus preventing bleeding.<ref> Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation: a possible ~~contrivutor~~ prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38-43. </ref> While this study did not directly measure intragastric pH, it supports the idea that neutralized pH will increase platelet aggregation		*Landmark in vitro studies have shown that high intragastric pH may facilitate platelet aggregation, thus preventing bleeding.<ref> Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation: a possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38-43. </ref> While this study did not directly measure intragastric pH, it supports the idea that neutralized pH will increase platelet aggregation.

	==Study Design==		==Study Design==
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	===Subgroup analysis===		===Subgroup analysis===



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	*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.		*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.
	*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>		*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>
	**~~The study likely has an overall increase~~ in ~~the rate~~ of ~~morbidity and mortality, compared to populations with any~~ bleeding peptic ulcers		**Past studies have shown that interobsrver agreement in peptic ulcer classification is poor to fair <ref>Lau JY1, Sung JJ, Chan AC, Lai GW, Lau JT, Ng EK, Chung SC, Li AK. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc. 1997 Jul;46(1):33-6.</ref>
	*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring		*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring
	**Previous studies in white patients have shown high doses of [[omeprazole]] to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>		**Previous studies in white patients have shown high doses of [[omeprazole]] to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>
	**Although this study specifically demonstrated the use of [[omeprazole]] after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.		**Although this study specifically demonstrated the use of [[omeprazole]] after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.
			===Further Discussion===
			*Meta-analysis of PPI initiation prior to endoscopy in patients with upper GI bleeding showed no clinically significant difference between PPI vs. placebo. <ref>Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010, Issue 7.</ref>
			**No significant difference in mortality, re-bleeding, or need for surgery
			**Use of omeprazole likely less important before endoscopy

	==Funding==		==Funding==

Catierey: further discussion

2015-09-28T17:10:52Z

further discussion

← Older revision		Revision as of 17:10, 28 September 2015
Line 105:		Line 105:

	==Criticisms & Further Discussion==		==Criticisms & Further Discussion==
			===Outcomes===
			*Composite primary outcome used: included vomiting, shock with melena, or drop of Hb>2 g/dL after transfusion to 10 g/dL
			**Hb of 10 g/dL no longer regarded as standard for transfusion threshold. A more conservative threshold of 7 g/dL has been shown to have overall benefit in the literature. <ref>Villanueva C. et al. "Transfusion strategies for acute upper gastrointestinal bleeding". NEJM. 2013. 368(1):11-21.</ref>
			**Studied end points may not directly translate to the emergency department, as the composite outcomes do not require the patient to be clinically sick.
			===Study Design===
	*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.		*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.
	*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>		*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>
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	*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring		*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring
	**Previous studies in white patients have shown high doses of [[omeprazole]] to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>		**Previous studies in white patients have shown high doses of [[omeprazole]] to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>
	**Although this study specifically demonstrated the use of [[omeprazole]] after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.		**Although this study specifically demonstrated the use of [[omeprazole]] after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.



	==Funding==		==Funding==

Ostermayer: /* Funding */

2015-09-23T13:30:39Z

Funding

← Older revision		Revision as of 13:30, 23 September 2015
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	==Funding==		==Funding==
	Supported in full by a grant from the Research Grants council of the Hong Kong Special Administration Region		Supported in full by a grant from the Research Grants council of the Hong Kong Special Administration Region

			==External Links==
			*[http://www.smartem.org/podcasts/upper-gi-bleed-2 SMART EM - PPI]
			*[http://www.smartem.org/podcasts/upper-gi-bleed-ppi SMART EM - PPI #2]

	==Sources==		==Sources==

Catierey: added internal links

2015-09-22T16:08:19Z

added internal links

← Older revision		Revision as of 16:08, 22 September 2015
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	{{JC info		{{JC info
	\| title=Effect of Intravenous ~~Omeprazole~~ on Recurrent Bleeding after Endoscopic Treatment of Bleeding Peptic Ulcer		\| title=Effect of Intravenous [[omeprazole]] on Recurrent Bleeding after Endoscopic Treatment of Bleeding Peptic Ulcer
	\| published=2000-08-03		\| published=2000-08-03
	\| author=Lau JYW, et al		\| author=Lau JYW, et al
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	==Clinical Question==		==Clinical Question==
	Does high dose intravenous omeprazole reduce the incidence of recurrent bleeding in patients who have undergone endoscopic intervention for bleeding peptic ulcers?		Does high dose intravenous [[omeprazole]] reduce the incidence of recurrent bleeding in patients who have undergone endoscopic intervention for bleeding peptic ulcers?

	==Conclusion==		==Conclusion==
	High-dose infusion of omeprazole after endoscopic treatment of bleeding peptic ulcers substantially reduces the risk of recurrent bleeding.		High-dose infusion of [[omeprazole]] after endoscopic treatment of bleeding peptic ulcers substantially reduces the risk of recurrent bleeding.

	==Major Points==		==Major Points==
	*Bleeding recurrence in 30 days was 6.7% (8 patients) in the omeprazole group, and 22.% (27 patients) in the placebo group, with bleeding most commonly occurring in the first 3 days after treatment.		*Bleeding recurrence in 30 days was 6.7% (8 patients) in the [[omeprazole]] group, and 22.% (27 patients) in the placebo group, with bleeding most commonly occurring in the first 3 days after treatment.
	**Hazard ratio: 3.9 (95% CI 1.7-9.0)		**Hazard ratio: 3.9 (95% CI 1.7-9.0)
	**Study stopped early due to significant difference between omeprazole and placebo (P<0.001)		**Study stopped early due to significant difference between [[omeprazole]] and placebo (P<0.001)
	*In vitro studies have shown that high intragastric pH could facilitate platelet aggregation, thus preventing bleeding.<ref> Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation: a possible contrivutor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38-43. </ref> While this study did not directly measure intragastric pH, it supports the idea that neutralized pH will increase platelet aggregation		*In vitro studies have shown that high intragastric pH could facilitate platelet aggregation, thus preventing bleeding.<ref> Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation: a possible contrivutor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38-43. </ref> While this study did not directly measure intragastric pH, it supports the idea that neutralized pH will increase platelet aggregation

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	*Patients underwent endoscopy within 24 hours after admission		*Patients underwent endoscopy within 24 hours after admission
	**Patients with actively bleeeding ulcers or ulcers with nonbleeding visible vessels were treated with local epi injection followed by thermocoagulation		**Patients with actively bleeeding ulcers or ulcers with nonbleeding visible vessels were treated with local epi injection followed by thermocoagulation
	*After hemostasis achieved, patients were randomly assigned in double-blind fashion to receive omeprazole or placebo (details in interventions).		*After hemostasis achieved, patients were randomly assigned in double-blind fashion to receive [[omeprazole]] or placebo (details in interventions).
	*After infusion, all patients were given 20 mg omeprazole PO daily for 8 weeks		*After infusion, all patients were given 20 mg [[omeprazole]] PO daily for 8 weeks
	*Primary end point was recurrent bleeding within 30 days after endoscopy		*Primary end point was recurrent bleeding within 30 days after endoscopy
	**Bleeding was considered to have recurred if any of the following occurred: vomiting of fresh blood, shock (SBP <90 mm Hg or HR >110) with melena after stabilization, or a drop of Hb >2 g/dL within 24 hours after a transfusion to 10 g/dL		**Bleeding was considered to have recurred if any of the following occurred: vomiting of fresh blood, shock (SBP <90 mm Hg or HR >110) with melena after stabilization, or a drop of Hb >2 g/dL within 24 hours after a transfusion to 10 g/dL
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	==Population==		==Population==
	===Patient Demographics===		===Patient Demographics===
	'''Omeprazole vs. Placebo''' <br/>		'''[[Omeprazole]] vs. Placebo''' <br/>
	Male: 66.7% vs. 66.7% <br/>		Male: 66.7% vs. 66.7% <br/>
	Age: 64 vs. 67 <br/>		Age: 64 vs. 67 <br/>
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	==Interventions==		==Interventions==
	*After endoscopic treatment, patients were randomly assigned to receive an intravenous infusion of placebo or omeprazole		*After endoscopic treatment, patients were randomly assigned to receive an intravenous infusion of placebo or [[omeprazole]]
	**Infusion given as an 80-mg bolus injection followed by a continuous infusion of 8 mg per hour for a period of 72 hours.		**Infusion given as an 80-mg bolus injection followed by a continuous infusion of 8 mg per hour for a period of 72 hours.
	**Identical-appearing vials of omeprazole and placebo were prepared by pharmacy with random numbers in blocks of 80		**Identical-appearing vials of [[omeprazole]] and placebo were prepared by pharmacy with random numbers in blocks of 80
	**Eligible patients were given the lowest-numbered treatment package		**Eligible patients were given the lowest-numbered treatment package
	**Treatment was started in the recovery area of the endoscopy suite and continued in a surgical ward		**Treatment was started in the recovery area of the endoscopy suite and continued in a surgical ward
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	===Primary Outcome===		===Primary Outcome===
	*Bleeding recurred within 30 days after treatment in 8 patients (6.7%) in omeprazole group, as compared with 27 (22.5%) in the placebo group.		*Bleeding recurred within 30 days after treatment in 8 patients (6.7%) in [[omeprazole]] group, as compared with 27 (22.5%) in the placebo group.
	*Hazard ratio: 3.9 (95% CI 1.7-9.0)		*Hazard ratio: 3.9 (95% CI 1.7-9.0)
	*Recurrent bleeding most common in first 3 days: 4.2% in omeprazole vs. 20% in placebo		*Recurrent bleeding most common in first 3 days: 4.2% in [[omeprazole]] vs. 20% in placebo

	===Secondary Outcomes===		===Secondary Outcomes===
	*Mean number of units transfused after endoscopy was significant smaller in omeprazole group (1.7 vs. 2.4 units, P=0.03)		*Mean number of units transfused after endoscopy was significant smaller in [[omeprazole]] group (1.7 vs. 2.4 units, P=0.03)
	**Mean number of units transfused before treatment was similar in the groups (1.0 vs. 1.1, P=0.46)		**Mean number of units transfused before treatment was similar in the groups (1.0 vs. 1.1, P=0.46)
	*Significantly more patients in the omeprazole group had a hospital stay <5 days (46.7% vs. 31.7%, P=0.02)		*Significantly more patients in the [[omeprazole]] group had a hospital stay <5 days (46.7% vs. 31.7%, P=0.02)
	*No significant difference in patients who underwent surgery (2.5% in omeprazole group vs. 7.5% in placebo group, P=0.14)		*No significant difference in patients who underwent surgery (2.5% in [[omeprazole]] group vs. 7.5% in placebo group, P=0.14)
	*No significant difference in patients who died within 30 days after endoscopy (4.2% in omeprazole group vs. 10% in placebo group, P=0.13)		*No significant difference in patients who died within 30 days after endoscopy (4.2% in [[omeprazole]] group vs. 10% in placebo group, P=0.13)


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	**The study likely has an overall increase in the rate of morbidity and mortality, compared to populations with any bleeding peptic ulcers		**The study likely has an overall increase in the rate of morbidity and mortality, compared to populations with any bleeding peptic ulcers
	*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring		*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring
	**Previous studies in white patients have shown high doses of omeprazole to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>		**Previous studies in white patients have shown high doses of [[omeprazole]] to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>
	**Although this study specifically demonstrated the use of omeprazole after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.		**Although this study specifically demonstrated the use of [[omeprazole]] after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.

Catierey: spacing

2015-09-21T17:45:33Z

spacing

← Older revision		Revision as of 17:45, 21 September 2015
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	\| status=Under Review		\| status=Under Review
	}}		}}


	==Clinical Question==		==Clinical Question==

Catierey: further discussion

2015-09-21T17:44:13Z

further discussion

← Older revision		Revision as of 17:44, 21 September 2015
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	==Major Points==		==Major Points==
	*Bleeding recurrence in 30 days was 6.7% (8 patients) in the omeprazole group, and 22.% (27 patients) in the placebo group		*Bleeding recurrence in 30 days was 6.7% (8 patients) in the omeprazole group, and 22.% (27 patients) in the placebo group, with bleeding most commonly occurring in the first 3 days after treatment.
	*In vitro studies have shown that high intragastric pH could facilitate platelet aggregation, thus preventing bleeding.<ref> Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation: a possible contrivutor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38-43. </ref>		**Hazard ratio: 3.9 (95% CI 1.7-9.0)
			**Study stopped early due to significant difference between omeprazole and placebo (P<0.001)
			*In vitro studies have shown that high intragastric pH could facilitate platelet aggregation, thus preventing bleeding.<ref> Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation: a possible contrivutor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38-43. </ref> While this study did not directly measure intragastric pH, it supports the idea that neutralized pH will increase platelet aggregation

	==Study Design==		==Study Design==
	*Randomized, double-blind, placebo-controlled study		*Randomized, double-blind, placebo-controlled study
	*Patients underwent endoscopy within 24 hours after admission		*Patients underwent endoscopy within 24 hours after admission
	*Patients with actively bleeeding ulcers or ulcers with nonbleeding visible vessels were treated with local epi injection followed by thermocoagulation		**Patients with actively bleeeding ulcers or ulcers with nonbleeding visible vessels were treated with local epi injection followed by thermocoagulation
	*After hemostasis achieved, patients were randomly assigned in double-blind fashion to receive omeprazole or placebo. (details in interventions)		*After hemostasis achieved, patients were randomly assigned in double-blind fashion to receive omeprazole or placebo (details in interventions).
	*After infusion, all patients were given 20 mg omeprazole PO daily for 8 weeks		*After infusion, all patients were given 20 mg omeprazole PO daily for 8 weeks
	*Primary end point was recurrent bleeding within 30 days after endoscopy		*Primary end point was recurrent bleeding within 30 days after endoscopy
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	===Inclusion Criteria===		===Inclusion Criteria===
	*~~Admitted~~ to Prince of Wales Hospital from May 1998 to July 1999 with bleeding peptic ulcers		*Patients admitted to Prince of Wales Hospital from May 1998 to July 1999 with bleeding peptic ulcers
	*>16 years		*>16 years old
	*Patients with successful endoscopic treatment of actively bleeding ulcers or ulcers with nonbleeding visible vessels		*Patients with successful endoscopic treatment of actively bleeding ulcers or ulcers with nonbleeding visible vessels

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	*Unsuccessful endoscopic treatment, requiring immediate surgery		*Unsuccessful endoscopic treatment, requiring immediate surgery
	*Ulcers with clean bases or flat pigments on endoscopy, therefore not requiring endoscopic treatment		*Ulcers with clean bases or flat pigments on endoscopy, therefore not requiring endoscopic treatment
	*10 ~~patients excluded due to terminal cancer~~		*Terminal cancer (n=10)
	*~~9 patients excluded as they were moribund~~ from concomitant illnesses		*Moribund from concomitant illnesses (n=9)

	==Interventions==		==Interventions==
	*After endoscopic treatment, patients were randomly assigned to receive an intravenous infusion of placebo or omeprazole, given as an 80-mg bolus injection followed by a continuous infusion of 8 mg per hour for a period of 72 hours.		*After endoscopic treatment, patients were randomly assigned to receive an intravenous infusion of placebo or omeprazole
			**Infusion given as an 80-mg bolus injection followed by a continuous infusion of 8 mg per hour for a period of 72 hours.
	**Identical-appearing vials of omeprazole and placebo were prepared by pharmacy with random numbers in blocks of 80		**Identical-appearing vials of omeprazole and placebo were prepared by pharmacy with random numbers in blocks of 80
	**Eligible patients were given the lowest-numbered treatment package		**Eligible patients were given the lowest-numbered treatment package
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	===Secondary Outcomes===		===Secondary Outcomes===
	*Mean number of units transfused after endoscopy was significant smaller in ~~omepraole~~ group (1.7 vs. 2.4 units, P=0.03)		*Mean number of units transfused after endoscopy was significant smaller in omeprazole group (1.7 vs. 2.4 units, P=0.03)
	**Mean number of units transfused before treatment was similar in the groups (1.0 vs. 1.1, P=0.46)		**Mean number of units transfused before treatment was similar in the groups (1.0 vs. 1.1, P=0.46)
	*Significantly more patients in the omeprazole group had a hospital stay <5 days (46.7% vs. 31.7%, P=0.02)		*Significantly more patients in the omeprazole group had a hospital stay <5 days (46.7% vs. 31.7%, P=0.02)
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	==Criticisms & Further Discussion==		==Criticisms & Further Discussion==
	*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.		*Study intended to recruit 320 patients and to conduct four interim analysis. However, the trial was terminated after the third planned interim analysis with 240 patients because a significant different (P<0.001) between the groups.
			*Researchers chose to exclude patients with flat pigments or clean bases seen on endoscopy, due to their low risk of recurrent bleeding <ref> Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol 1995;21:103-6. </ref>
			**The study likely has an overall increase in the rate of morbidity and mortality, compared to populations with any bleeding peptic ulcers
			*The researchers propose that decreased intragastric pH leads to decreased re-bleeding, however this was not directly measured with pH monitoring
			**Previous studies in white patients have shown high doses of omeprazole to neutralize intragastric pH. <ref> Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Borsch G. Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study. Gut 1997;40:36-41 </ref>
			**Although this study specifically demonstrated the use of omeprazole after endoscopic treatment, the principle can be translated to use in the emergency department for patients with bleeding peptic ulcers.