Do all ICU patients need Stress Ulcer Prophylaxis?

Introduction

Patients who are admitted to ICU may suffer from Stress Ulceration, which is the development of superficial ulcers in the upper gastrointestinal (GI) tract. This differs from the reactivation of chronic duodenal or gastric ulcers as it is caused by either hypersecretion of gastric acid or impaired mucosal protection. Thus, most patients admitted to the ICU receive Stress Ulcer Prophylaxis (SUP). But first, let us know about Stress Ulcer categories (see table 1).

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Table 1: Stress Ulcer Categories
Category	Definition	Incidence
Stress ulceration with occult bleeding	Fecal samples with guaiac-positive test for blood	15% - 50%
Stress ulceration with overt gastrointestinal bleeding	Hematemesis, bloody nasogastric tube aspirate, or melena	1.5% - 8.5%
Stress ulceration with clinically important gastrointestinal bleeding	Overt gastrointestinal bleeding plus one or more of the following within 24 hours: Decrease in systolic, diastolic, or mean arterial blood pressure of ≥ 20 mm Hg Orthostatic hypotension or postural tachycardia Drop in hemoglobin ≥ 2 g/dL Received transfusion of ≥ 2 units of packed RBCs Need for vasopressors or invasive intervention (e.g., endoscopy)	1% - 3%

Keep in mind...

1. Around 75% of patients do not receive SUP, however, only a minority of these ulcers bleed.
2. Mechanical ventilation for more than 48 hours and coagulopathy are the major 2 risks for developing SUP and GI bleeding.
3. SUP has not been shown to decrease mortality rate, however, it decreases both the risk of clinically significant bleeding and the risk of Clostridioides difficile infection or pneumonia.

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Patients at increased risk

Stress Ulcer suspected in patients who suffer from hematemesis, melena, anemia, or hypotension. Multiple risk factors linked to stress ulcer risk (see table 2).

Table 2: Risk factors linked to stress ulcer
Major risk factors (prophylaxis recommended)
Positive pressure ventilation > 48 hours Coagulopathy (platelet count < 50 x 109/L, INR > 1.5, APTT > 2 times normal) History of gastrointestinal ulceration or bleeding within past year Acute traumatic brain or spinal cord injury
Minor risk factors (prophylaxis recommended if ≥ 2 minor criteria are present)
Sepsis ICU stay > 1 week Occult gastrointestinal bleeding for ≥ 6 days Glucocorticoid therapy (> 250 mg hydrocortisone or the equivalent) Use of antiplatelet or NSAIDs Renal failure or renal replacement therapy Hepatic failure History of peptic ulcer disease Organ transplantation

The best agent to use

SUP medication includes Proton-Pump Inhibitors (PPIs), Histamine-2 receptor blockers (H2-blockers), and Sucralfate. The optimal prophylactic agent in clinical practice remains uncertain and the choice of prophylactic medication should be tailored to the patient’s need, comorbidities, and potential risk of C. difficle infection and pneumonia.

The favorable choice for clinicians is PPIs. Although PPIs effectively prevent GI bleeding over H2-blockers, there has been a concern for increased risk of pneumonia & C. difficle infection. However, the PEPTIC trial (Proton Pump Inhibitors vs Histamine-2 Receptor Blockers for Ulcer Prophylaxis Treatment in the Intensive Care Unit) largely dispelled this concern after discovering that there is no increase neither in C. difficle infection (0.3% with PPIs vs. 0.43% with H2-blocker; RR 0.74 (95%), CI 0.51-1.09) nor pneumonia (6.5% with a PPI vs 5.8% with a histamine-2 receptor blocker; RR 1.18 (95%) CI 0.87-1.59). Table 3 shows the recommended dose for each drug.

*RR = Relative Risk (the ratio of the probability of an outcome in an intervention group to its probability in a control group).
*CI = Confidence Interval (embraces the value of no difference between treatments indicating that the treatment under investigation is not significantly different from the control).

Table 3: Recommended SUP medications doses
Route	PPIs	H2-blocker	Sucralfate
Parenteral	Pantoprazole 40 mg/day Esomeprazole 40 mg/day	Famotidine 20 mg/12 hrs.
Enteral	Pantoprazole 40 mg/day Esomeprazole 40 mg/day Omeprazole 40 mg/day Lansoprazole 30 mg/day	Famotidine 20 mg/12 hrs. Cimetidine 300 mg/6 hrs. Ranitidine 150 mg/12 hrs. (removed from market)	Sucralfate 1g/6 hrs.

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When to stop SUP?

There is no clear optimal duration for SUP, however, most experts agree that prophylaxis should be continued whenever risk factors are present and there is a greater consensus on discontinuing SUP for non-ICU hospitalized patients as they are at minimal risk of developing stress ulcers.

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References

1. Walker M, Leonard, Kyle JA. Stress Ulcer Prophylaxis Within the ICU. US Pharm. 2023; 48(12): HS2-HS10.
2. Saeed, Mariam et al. “Which ICU patients need stress ulcer prophylaxis?.” Cleveland Clinic journal of medicine vol. 89,7 363-367.
3. PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group et al. “Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial.” JAMA vol. 323,7 (2020): 616-626.

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