PPIs for the Management of Upper GI Bleed


  1. Upper GI bleed (UGIB) is a common reason for ED visits with a major cause of morbidity, mortality and medical care costs.
  2. Peptic ulcer accounts for at least 50% of UGIB cases.
  3. Patients with UGIB usually present with hematemesis, melena and/or hematochezia.
  4. Upon presentation, hemodynamic status should be evaluated and resuscitation provided if necessary. Resuscitation can include blood transfusion for target hemoglobin of ≥7 g/dl.
  5. Patients can be risk stratified to low or high-risk using the Rockall score (range 0-7) and Blatchford score (range 0-23).
  6. Proton pump inhibitors (PPIs) remain one of the mainstays of pharmacological therapy for the management of UGIB. It can be initiated if endoscopy cannot be performed, will be delayed for >24 after presentation or following endoscopy.

DoseInitial Infusion: 80mg bolus then 8mg/hr continuous infusion for a total of 72hours Intermittent: 80mg LD then 40mg IVP Q12H   Maintenance High-risk: 40mg PO BID for 14days, then 40mg PO once daily  Low-risk: 20mg PO once daily   *Duration ranges from 4-12weeks Initial Infusion: 80mg bolus then 8mg/hr continuous infusion for a total of 72hours Intermittent: 80mg LD then 40mg IVP Q12H   Maintenance High-risk: 40mg PO BID for 14days, then 40mg PO once daily  Low-risk: 20mg PO once daily   *Duration ranges from 4-12weeksInitial IV Omeprazole not available in the U.S, give IV Pantoprazole or Esomeprazole   Maintenance High-risk: 40mg PO BID for 14days, then 40mg PO once daily Low-risk: 20mg PO once daily   *Duration ranges from 4-12weeks
AdministrationIVP: Give over at least 2 minutes   Continuous Infusion: 8mg/hr   PO: Swallow whole without crushing or splitting 30-60minutes before foodIVP: Give over at least 3 minutes for dose <80 mg; Loading dose over 30 minutes   Continuous Infusion: 8mg/hr   PO: Capsule can be given orally or opened and mixed with 50mL water for NG administrationPO: Swallow whole without crushing or splitting 30-60minutes before food
PK/PDOnset: IV 15 to 30 minutes, PO 2.5hrs Absorption: Rapid, well absorbed Duration: 24hours (IV and PO)  Distribution: 98% albumin bound Half-life elimination: 1hr, 3.5-10hrs in CYP2C19 deficiency Excretion: Urine (71%), feces (18%)Distribution: 97% protein bound Metabolism: Hepatic primarily via CYP2C19 Half-life elimination: 1 to 1.5hrs in adults Excretion: Urine (80%), 20% fecesOnset: PO 1hr Absorption: Rapid Duration: Up to 72hours  Distribution: 95% albumin bound Half-life elimination: 30min – 1hr, 3 hrs in hepatic impairment Excretion: Urine (77%)
Adverse EffectsHeadache, nausea, abdominal pain, diarrhea, vomitingHeadache, flatulence, nausea, dyspepsia, abdominal pain, diarrheaHeadache, abdominal pain, nausea, diarrhea, vomiting, flatulence 
Drug Interactions & WarningsContraindicated with Atazanavir,  Rilpivirine and their combinationsContraindicated with Atazanavir,  Rilpivirine and their combinations, CYP2C19 InducersContraindicated with Atazanavir, Rilpivirine and their combinations, CYP2C19 Inducers
CompatibilityCompatible with D5W, NS or LRCompatible with D5W, NS or LRNot Applicable
Comments: PPIs may increase the risk of Clostridium difficile associated diarrhea – use lowest dose and shortest duration where possible 

Overview of Evidence

Author, yearDesign &  Sample SizeIntervention &  ComparisonOutcomes
Daneshmend et al., 1992Double-blind, placebo- controlled, parallel study (n=1147)Omeprazole 80mg IV bolus followed by 40mg IV every 8hr x3, then 40mg PO twice daily vs placebo Treatment started within 12h of admission, continued for 4 days or until surgery, discharge or deathNo significant differences between placebo and omeprazole for blood transfusions (53% v 52%), rebleeding (18% v 15%), surgery (11% v 11%) and death (5.3% v 6.9%) Significant reduction in signs of UGIB observed during endoscopy with omeprazole (33%) vs placebo (45%); p < 0.0001
Andriulli et al., 2008Randomized, multicenter double-blind study (n=474)PPI Continuous (80mg bolus followed by 8mg/hr infusion for 72hr) PPI Intermittent (40mg IV bolus daily for 72hr) Switched to oral PPI (20 mg twice daily) after 72hr and continued until discharge Used Pantoprazole and OmeprazoleBleeding recurred in 11.8% continuous regimen vs 8.1% in the intermittent regimen; P = 0.18 7.6% vs 8.1% rebleeding during first 72hr in the continuous vs intermittent group; P = 0.32  Patients in the continuous group had a prolonged hospital stay > 5 days (P = 0.03)
Sung et al., 2009Randomized, multicenter double-blind study (n=764)Esomeprazole 80mg IV bolus followed by 8mg/hr  Placebo, continued for 72hr after endoscopic hemostasis o      Both groups received esomeprazole PO 40mg daily for 27days after infusion Esomeprazole had less recurrent bleeding within 72hr compared to placebo (5.9% vs 10.3%). Findings remained significant at day 7 and day 30; p = 0.010 Esomeprazole decreased endoscopic re-treatment (6.4% vs 11.6%), need for surgery (2.7% vs 5.4%) and mortality (0.8% vs 2.1%)
Sreedharan et al., 2010Systematic review and meta-analysis (6RCTs, n=2223)  Active treatment with a PPI (oral or IV) and control with either placebo, histamine-2 receptor antagonist or no treatment before endoscopyPPI before endoscopy did not decrease mortality (OR 1.12 95% CI 0.72-1.73), rebleeding (OR 0.81, 95% CI 0.61- 1.09) or the need for surgery (OR 0.96, 95% CI 0.68-1.35) PPIs significantly decreased the number of patients with stigmata of recent hemorrhage at endoscopy PPIs compared to control significantly reduced endoscopic intervention
Chen et al.,  2012Prospective, randomized control trial (n=201)Pantoprazole 80mg IV bolus then 8mg/hr  Pantoprazole 40mg IV bolus once daily for 72hr o      Both groups received pantoprazole 40mg daily PO for 27days after 72hrNo statistical differences in units of blood transfused, length of hospital stay, surgical/radiological interventions and mortality within 30 days High-dose PPI regimen was not superior in the reduction of recurrent bleeding at 30 days as compared with a standard-dose regimen
Sachar et al., 2014Systematic review and meta-analysis (13RCTs)Intermittent doses of PPIs (IV or PO)  80mg IV bolus followed by 8mg/hr for 72hoursIntermittent PPI regimens were comparable and are non-inferior to continuous PPI infusion regimens in patients with bleeding ulcers and high-risk endoscopic findings. There is no difference in recurrent bleeding with intermittent vs continuous PPI therapy
Rattanasupar et al., 2016Prospective, randomized control trial (n=113)Pantoprazole 80mg IV bolus then 8mg/hr Pantoprazole 40mg IV twice daily No difference in average time of hospital stay (3.03 vs 2.89 days, p>0.05) and mean amount of blood transfused (1.79 vs 1.63 units, p>0.05) between continuous and intermittent pantoprazole No statistically significant difference in terms of recurrent bleeding and mortality between both groups (p>0.05) Blatchford score greater than 10, 11, and 12 showed high sensitivity of predicting high-risk peptic ulcer bleeding


  1. Compared to placebo or other non-PPI treatment measures, evidence suggests PPI therapy did not reduce the need for blood transfusion, rebleeding rate, surgery or death.
  2. Compared to placebo, PPIs reduced the signs of upper gastrointestinal bleeding observed during endoscopy and reduced the need for endoscopic treatment. 
  3. Administration of a PPI as continuous infusion did not impact patient outcomes and is not superior to intermittent therapy; however, high dose PPI may be considered in patients with Blatchford scores greater than 12.


  1. Clinical Pharmacology [Electronic version]. Elsevier, 302 Knights Run Ave., Suite 800, Tampa, FL 33602. Retrieved February 17, 2021, from http://www.clinicalpharmacology-ip.com/
  2. Uptodate [Electronic version]. Retrieved February 15, 2021, from http://www.uptodate.com/
  3. Laine, Loren MD; Jensen, Dennis M MD. Management of Patients With Ulcer Bleeding, American Journal of Gastroenterology: March 2012 – Volume 107 – Issue 3 – p 345-360 
  4. Daneshmend, T. K., Hawkey, C. J., Langman, M. J., Logan, R. F., Long, R. G., & Walt, R. P. (1992). Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. BMJ (Clinical research ed.), 304(6820), 143–147.  
  5. Andriulli, A., Loperfido, S., Focareta, R., Leo, P., Fornari, F., Garripoli, A., Tonti, P., Peyre, S., Spadaccini, A., Marmo, R., Merla, A., Caroli, A., Forte, G. B., Belmonte, A., Aragona, G., Imperiali, G., Forte, F., Monica, F., Caruso, N., & Perri, F. (2008). High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study. The American journal of gastroenterology, 103(12), 3011–3018.  
  6. Sung JJ, Barkun A, Kuipers EJ, et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2009; 150(7):455-464.  
  7. Sreedharan, A., Martin, J., Leontiadis, G. I., Dorward, S., Howden, C. W., Forman, D., & Moayyedi, P. (2010). Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. The Cochrane database of systematic reviews, 2010(7), CD005415.  
  8. Chen CC, Lee JY, Fang YJ, et al. Randomised clinical trial: high-dose vs. standard-dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers. Aliment Pharmacol Ther. 2012; 35(8):894-903.  
  9. Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med. 2014; 174(11):1755-1762.
  10. Rattanasupar A, Sengmanee S. Comparison of High Dose and Standard Dose Proton Pump Inhibitor before Endoscopy in Patients with Non-Portal Hypertension Bleeding. J Med Assoc Thai. 2016; 99(9):988-995.

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