Stress Ulcer Prophylaxis Revisited:Why “Just Start a PPI” No Longer Holds Up

One of the most common questions that seems to always come up on rounds is, "Does this patient need GI prophylaxis?" Depending on who's rounding, the day or the experience, a different answer will come. Why is this? Maybe training or experience play a role in this. We can look at the recommendations based on training.

Comparing Surgical Guidelines, SCCM/ASHP Recommendations, and the REVISE Trial

Stress ulcer prophylaxis (SUP) in critically ill patients has been a standard ICU practice for decades. Historically, SUP was often started reflexively—intubate a patient, initiate a proton pump inhibitor (PPI). However, advances in critical care, including earlier enteral nutrition, improved resuscitation, and lung-protective ventilation strategies, have significantly reduced the incidence of clinically significant upper gastrointestinal bleeding (UGIB).

As a result, SUP has moved from a default ICU order to an area of active reassessment. Clinicians today must reconcile guidance from:

• Surgical and trauma literature, including recommendations from the Eastern Association for the Surgery of Trauma (EAST)

• The 2024 clinical practice guideline from the Society of Critical Care Medicine and the American Society of Health-System Pharmacists

• Contemporary randomized trials, most notably the REVISE trial published in The New England Journal of Medicine

While these sources share common principles, they diverge in patient selection, duration of therapy, and emphasis on deprescribing.

Why Stress Ulcer Prophylaxis Guidelines Are Being Revisited

The publication of the REVISE trial alongside the updated 2024 SCCM/ASHP guideline on stress ulcer prophylaxis has reshaped clinical conversations.

The central issue in 2026 is no longer whether SUP can prevent GI bleeding—it can—but how to balance bleeding prevention against risks such as ventilator-associated pneumonia (VAP), Clostridioides difficile infection (CDI), and inappropriate continuation beyond the ICU.

Where Current SUP Guidelines Agree

SUP Should Be Risk-Based, Not Automatic

Modern guidelines agree that routine SUP for all ICU patients is not evidence-based. Clinically important UGIB is relatively uncommon in contemporary ICUs, and prophylaxis should be reserved for patients with clearly defined bleeding risk factors, as emphasized in the SCCM/ASHP guideline.

Proton Pump Inhibitors vs H2 Receptor Antagonists

Both PPIs and H2 receptor antagonists remain acceptable agents for SUP. Current evidence does not support universal superiority of one class over the other. Selection should be individualized based on:

• Route of administration

• Drug–drug interactions

• Infection risk profile

• Institutional formulary considerations

SUP Is Not Without Risk

Across surgical and medical literature, acid suppression has been associated with:

• Ventilator-associated pneumonia (VAP)

• Clostridioides difficile infection (CDI)

• Medication inertia, where SUP continues after ICU-level illness has resolved

Surgical and Trauma Guidance: EAST and SICU Practice

The EAST Practice Management Guideline for stress ulcer prophylaxis reflects a pragmatic, historically protective approach shaped by trauma and postoperative populations.

Common features include:

• SUP recommended for critically ill surgical and trauma patients

• Mechanical ventilation frequently included as a risk factor

• Enteral nutrition alone not considered sufficient prophylaxis

• SUP commonly continued throughout the ICU stay

• Broad agent selection influenced by cost and availability

This framework prioritizes bleeding prevention during periods of maximal physiologic stress, with less explicit emphasis on early deprescribing.

SCCM/ASHP 2024: A Deprescribing-Focused Shift

In contrast, the 2024 SCCM/ASHP clinical practice guideline adopts a more selective, safety-focused stance.

Key distinctions include:

• Mechanical ventilation alone is not a firm indication for SUP

• Greater emphasis on bleeding risk factors such as coagulopathy, shock, and chronic liver disease

• Recognition that enteral nutrition likely reduces UGIB risk

• Strong recommendations for daily reassessment and discontinuation once risk factors resolve

• Explicit guidance to avoid continuation of SUP at ICU transfer or hospital discharge

This reframes SUP as a temporary, indication-driven therapy, rather than a standing ICU order.

What the REVISE Trial Adds to SUP Decision-Making

The REVISE trial, the largest modern randomized trial of SUP in invasively ventilated adults, provides contemporary data.

Key findings:

• IV pantoprazole reduced clinically important upper GI bleeding

• No improvement in mortality

• No clear increase in VAP or CDI within the trial period

REVISE supports SUP use in selected high-risk patients, particularly those requiring invasive mechanical ventilation, but does not justify routine or prolonged prophylaxis.

Practical ICU Takeaway

Modern stress ulcer prophylaxis is not about choosing PPI versus H2RA. It is about daily clinical reassessment:

1. Does the patient still have meaningful bleeding risk?

2. Is enteral nutrition established with low residual risk?

3. Can SUP be discontinued today—especially before ICU transfer?

In contemporary critical care, the safest SUP strategy is measured initiation, continuous reassessment, and intentional discontinuation.

My biggest takeaway is that starting EN within the first day can either negate the need for prophylaxis in the majority of patients. At the minimum it provides the ability to stop SUP earlier in low to moderate risk patients.

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