Stress Ulcer Prophylaxis

Original Date: 04/2012 | Supersedes: 04/2013, 08/2017 | Last Review Date: 06/2021
Purpose: Assist in identification of patients who may benefit from stress ulcer prophylaxis.


Stress Ulcer Prophylaxis is indicated for select patients (Grade Level of Quality – moderate; USPSTF strength of recommendation – C [the intervention is recommended selectively based upon professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small]).

Stress ulcer prophylaxis should be given with the following conditions: 1,2

  • Mechanical Ventilation
  • Disease associated coagulopathy
  • Major burn injury >30% TBSA

Stress Ulcer Prophylaxis Agent Choice:

  1. Famotidine (H2 blocker):
    1. Dosing:
      • 20mg IV q 12H – in patients with no gastric/enteral access
      • 20mg PO/NGT q 12H– in patients with gastric feeds/gastric access only
    2. In patients on TPN, famotidine can be added to the TPN bag daily
  2. Proton Pump Inhibitors
    1. Dosing:
      • Pantoprazole 40mg IV q24 hours
      • Lansoprazole 30mg suspension NGT q 24 hours
    2. Limit use to:
      • Patients with overt and clinically significant GI bleeding
      • PPI use as outpatient


At the onset of risk factors.

Duration of Treatment

Until risk factors resolve


Gastrointestinal bleeding secondary to stress ulcer formation is a well-known complication of critical illness.  However, more recent data suggests that the incidence of clinically significant hemorrhage is decreasing over time.  It has become standard of care for patients to receive chemical stress ulcer prophylaxis if requiring mechanical ventilation, having coagulopathy, or suffering traumatic brain injury or major burns.

More recently, need for prophylaxis and medication of choice have come into question. With increasing popularity of proton pump inhibitors (PPI) as stress ulcer prophylaxis, concerns have risen regarding the risks of infection complications, such as C. difficile colitis and nosocomial pneumonia.  While no randomized trials have suggested a causative link between stress ulcer prophylaxis and infectious complications, several observational studies suggest such a correlation.

H2-receptor antagonists are commonly used and have shown similar efficacy in preventing clinically significant GI bleeding.  Sulcralfate is less commonly used, yet is thought to be equally efficacious in preventing stress ulcer formation and bleeding.

An ongoing, large, multicenter trial (Re-Evaluating the Inhibition of Stress Erosions, REVISE) comparing placebo to pantoprazole is currently underway which should help inform future practice.

Relevant Literature Search

Overall, mostly low quality data regarding these topics exists begging the need for a large multi-center randomized trial to help clarify these questions. A literature search was conducted in Pub Med using the search terms: “Stress Ulcer Prophylaxis”, “Critical Illness”, “Acid suppressing drugs” as outlined below.  Studies were limited to prospective randomized trials published with the last 10 years (since the 2008 EAST guideline upon with the last UTH guideline was based).

Risk Factors Preferred Agent for SUP Duration of SUP
Guillamondegui/2008 Level 1:

  • Mechanical ventilation
  • Coagulopathy
  • Traumatic brain injury
  • Major burn

Level 2:

  • Multi-trauma
  • Sepsis
  • Acute kidney injury

Level 3:

  • ISS>15
  • High dose steroids
Level 1:

  • No difference between H2 blocker, PPI, sucralfate

Level 2:

  • Sucralfate should not be used in patients on dialysis

Level 3:

  • Enteral feeding may be insufficient mono-prophylaxis
Level 1:

  • None

Level 2:

  • Duration of mechanical ventilation or ICU stay

Level 3:

  • Until able to tolerate enteral nutrition
Author/ Year Study Type Patients (n) Population Intervention Type Outcomes Results
PPI versus Placebo
Selvanderan/20163 RCT 214 Mixed medical-surgical ICU Pantoprazole vs placebo GIB, VAP, C diff Clin Sig GIB: 0% (PPI) vs 0% (Placebo)
Any GIB: 3% (PPI) vs 6% (Placebo)
VAP: 1% (PPI) vs 2% (Placebo)
C Diff: 1% (PPI) vs 0% (Placebo)
Lin/20164 RCT 120 Vented >48hrs, NGT, weaning ventilator Lansoprazole vs no acid reducer x 14d GIB, VAP, 30d survival Clin Sig GIB: 0% (PPI) vs 2% (Placebo)
Any GIB: 0% (PPI) vs 8% (Placebo)
VAP: 7% (PPI) vs 10% (Placebo)
Note: both studies have a lower rate of clinically significant bleeding than anticipated, which suggest issues of power and internal/external validity.
Liu/ 20135 RCT 165 Neurosurgical patients with ICH Omeprazole vs cimetidine vs placebo GIB, Death, PNA Any GIB: 16% (PPI) vs 28% (H2) vs 45% (Placebo), p=0.003
PNA: 24% (PPI) vs 22% (H2) vs 15% (Placebo), p=0.469
Note: use of any GIB as outcome and high rate of GIB in Placebo group brings generalizability of this study into question.

Cost Considerations

Famotidine 20mg IV q12 hours $X/day
Famotidine 20mg PO q12 hours $X/day
Ranitidine 150mg suspension q 12 hours $2.7X/day
Pantoprazole 40mg IV q24 hours $13.6X/day
Pantoprazole 40mg PO q24 hours (cannot be crushed) $0.8X/day
Pantoprazole 40mg packet q24 hours $32.8X/day
Lansoprazole 30mg suspension q24 hours $11.7X/day

Actual costs cannot be displayed. However, the costs of different regimens are provided in the form of multiples of the cost of famotidine.

Appendix A: Search Strategy

Search Database Search Terms Limits Articles Excluded articles Included articles
1 Pub Med stress ulcer prophylaxis Randomized Controlled Trial, 10 years, English language 9 6 (2 protocols, 2 surrogate outcomes, 2 off topic) 3
2 Pub Med stress ulcer prophylaxis AND intensive care Randomized Controlled Trial, 10 years, English language 6 5 1 (duplicate)
3 Pub Med Stress ulcer prophylaxis AND acid suppressing drugs Randomized Controlled Trial, 10 years, English language 0 0 0


1 Cook, D.J., Fuller, H.D., Guyatt, G.H., et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Groups. New England Journal of Medicine. 1994; 330(6): 377-381
2 Guillamondegui, O., Gunter, O.L., Bonadies, J.A. et al. Practice management guidelines for stress ulcer prophylaxis. EAST Practice Management Guidelines Committee. 2008
3 Selvanderan, Shane P., Matthew J. Summers, Mark E. Finnis, Mark P. Plummer, Yasmine Ali Abdelhamid, Michael B. Anderson, Marianne J. Chapman, Christopher K. Rayner, and Adam M. Deane. “Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP).” Critical Care Medicine 44.10 (2016): 1842-850
4 Lin, Chien-Chu, et al. “Stress ulcer prophylaxis in patients being weaned from the ventilator in a respiratory care center: A randomized control trial.” Journal of the Formosan Medical Association, vol. 115, no. 1, 2016, pp. 19–24
5 Liu, Bo-Lin, Bing Li, Xiang Zhang, Zhou Fei, Shi-Jie Hu, Wei Lin, Da-Kuan Gao, and Li Zhang. “A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral hemorrhage.” Journal of Neurosurgery 118.1 (2013): 115-20