SCCM and ASHP Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults

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Robert MacLaren, PharmD, MPH, MCCM Joanna C. Dionne, MD, PhD, MSc Waleed Alhazzani, MD, MSc
PUBLISHED: 07/15/2024

Citation: MacLaren R, Dionne J, Granholm, A, et al. Society of Critical Care Medicine and American Society of Health-System Pharmacists guideline for the prevention of stress-related gastrointestinal bleeding in critically ill adults. Crit Care Med. 2024 Aug;52(8):e421-e430.

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RATIONALE: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB).

OBJECTIVES: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU.

DESIGN: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting.

METHODS: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance.

RESULTS: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing.

CONCLUSIONS: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient’s existing clinical status.

KEYWORDS: enteral nutrition; gastrointestinal bleeding; histamine 2 blockers; intensive care; proton pump inhibitors; stress ulcer prophylaxis

Guideline Type: Clinical

Related Resources:
Executive Summary: Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults

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We suggest critically ill adults with coagulopathy, shock, or chronic liver disease be considered at risk for clinically important UGIB.
Certainty of evidence: Low to moderate

We suggest clinicians administer enteral nutrition to reduce clinically important stress-related UGIB in critically ill adults compared with no enteral nutrition.
Certainty of evidence: Moderate

We suggest critically ill adults with coagulopathy, shock, or chronic liver disease be considered at risk for overt UGIB.
Certainty of evidence: Low to moderate

We suggest clinicians provide SUP to prevent clinically important UGIB in critically ill adults with risk factors compared with no SUP.
Certainty of evidence: Moderate

We suggest using SUP in neurocritical care adults to reduce clinically important stress-related UGIB compared with no SUP.
Certainty of evidence: Very low

We suggest using SUP for critically ill adults who are enterally fed and possess one or more risk factor(s) for clinically important stress-related UGIB compared with no SUP.
Certainty of evidence: Very low

We suggest not using SUP for critically ill adults who are enterally fed and at low risk for clinically important stress-related UGIB.
Certainty of Evidence: Very low

Concurrent administration of SUP with enteral nutrition may increase pneumonia risk.

We suggest using either PPIs or H2RAs as first-line agents for SUP in critically ill adults with risk factors for clinically important stress-related UGIB compared with no PPIs or H2RAs.
Certainty of Evidence: Moderate

Despite reducing the occurrence of clinically important UGIB with PPIs compared with H2RAs, there is uncertainty regarding the influence of PPIs on mortality in patients with high severity of illness in the ICU. Although recent subgroup assessments of randomized trials suggest an association between PPIs and increased mortality, our judgment is based on pooled analyses of all compiled aggregate data rather than pooled analyses of subgroup data.

We suggest using either enteral or IV routes when administering SUP in critically ill adults with risk factors for clinically important stress-related UGIB compared with no enteral or IV routes.
Certainty of Evidence: Low

Low dose SUP should be administered in critically ill adults with risk factors for clinically important stress-related UGIB compared with high-dose SUP.

“Low-dose” PPI therapy is defined as a daily dose of less than or equal to 40 mg esomeprazole, omeprazole, or pantoprazole and less than or equal to 30 mg lansoprazole. “Low-dose” H2RA therapy is defined as a daily dose of less than or equal to 40 mg famotidine, less than or equal to 150 mg IV ranitidine, less than or equal to 300 mg enteral ranitidine, and less than or equal to 1200 mg cimetidine. “Low-dose” sucralfate is defined as a daily dose of less than or equal to 4 g.

In critically ill adults with risk factors for developing clinically important stress-related UGIB, SUP should be discontinued when the risk factor(s) is no longer present. Discontinuation of SUP prior to transfer out of the ICU is necessary to prevent inappropriate prescribing.

In critically ill adults who do not have risk factors for developing clinically important stress-related UGIB but are on a SUP agent before ICU admission, the indications for these medications should be reviewed and consideration made for discontinuing them.

Some critically ill patients without risk factors for stress ulcers may continue to require SUP therapy received before ICU admission. The most common situations likely require stronger acid suppression with PPIs and include but are not limited to recent UGIB, hypersecretory states, erosive esophagitis, and eradication therapy of Helicobacter pylori infections. Therapy or prevention of anaphylaxis, angioedema, or urticaria may necessitate continuation of maintenance therapy of H2RA. The benefit of continuing these agents for maintenance therapy of their pre-ICU condition must be weighed against possible adverse events, drug interactions, and availability of the route of administration.

In critically ill adult patients with risk factors for developing clinically important stress-related UGIB and who are receiving a SUP agent before ICU, the consideration to change the medication to the most preferred agent for SUP must be weighed against the indication that required the SUP therapy before ICU admission.

Patient-specific factors such as allergies to a specific class of agents or potential severe drug interactions may necessitate the choice of a specific class of agents for SUP.

H2RA, histamine-2 receptor antagonist; PPI, proton pump inhibitor; SUP, stress ulcer prophylaxis; UGIB, upper gastrointestinal bleeding.


Robert MacLaren, PharmD, MPH, MCCM
Author
Robert MacLaren, PharmD, MPH, MCCM
Robert MacLaren, PharmD, MPH, MCCM, is a professor in the Department of Clinical Pharmacy at the University of Colorado and clinical pharmacist in the medical ICU at the University of Colorado Hospital. He is a fellow of the American College of Clinical Pharmacy and Master of the Society of Critical Care Medicine.
Joanna C. Dionne, MD, PhD, MSc
Author
Joanna C. Dionne, MD, PhD, MSc
Joanna C. Dionne, MD, PhD, MSc, is an assistant professor in the Divisions of Critical Care Medicine and Gastroenterology, Department of Medicine and Department of Health Research Methods, Evidence and Impact at McMaster University. She served as a lead methodologist for the Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.
Waleed Alhazzani, MD, MSc
Author
Waleed Alhazzani, MD, MSc
Waleed Alhazzani, MD, MSc, is an associate professor of medicine, and health research methodology, evidence, and impact at McMaster University. He is a consultant intensivist and gastroenterologist at St. Joseph's Healthcare Hospital in Hamilton, Ontario, Canada. He served as a lead methodologist for the Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.

A complete list of the guidelines authors and contributors is available within the published manuscript.

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