Stress Ulcer Prophylaxis

Educational Objectives

The goal of this program is to improve management of stress ulceration. After hearing and assimilating this program, the clinician will be better able to:

1. Prescribe appropriate stress ulcer prophylaxis to prevent gastrointestinal bleeding.

Summary

Introduction: splanchnic hypoperfusion and mesenteric ischemia in critical illness can lead to reduced mucosal blood flow and stress gastropathy; in a small percentage of patients, this can lead to clinically important gastrointestinal (GI) bleeding (CIB; obvious physiologic decline, the need for transfusion, or the need for intervention with surgery or endoscopy); Hastings et al (1978) showed that antacids reduced the occurrence of GI bleeding; 2 meta-analyses demonstrated that histamine-2 receptor antagonists (H2RAs) and sucralfate decrease the rates of GI bleeding and stress ulceration

Risk factors: Cook et al (1994) demonstrated a 1.5% incidence of CIB in patients without stress ulcer prophylaxis (SUP), and the mortality rate was 5 times greater in patients who bled; respiratory failure requiring mechanical ventilation >48 hr and coagulopathy were identified as risk factors for CIB; 847 patients who had 1 or both risk factors had a 3.7% incidence of CIB vs 0.1% in patients with neither risk factor; Simons et al (1995) noted that 57 patients with major trauma developed CIB despite receiving SUP; injury severity score (ISS) ≥16, spinal cord injury, and age >55 yr were identified as the most important risk factors

Eastern Association for the Surgery of Trauma guidelines for SUP: level 1 recommendation — all patients with mechanical ventilation, coagulopathy, traumatic brain injury (TBI), or major burn injury; level 2 recommendation — all intensive care unit (ICU) patients with multiple traumatic injuries, sepsis, or acute renal failure; level 3 recommendation — all ICU patients with ISS >15 or requirement for high-dose steroids

SUP-associated complications: secondary to immunosuppressive effects of proton pump inhibitors (PPIs) and H2RAs; include, eg, pneumonia, Clostridium difficile infection (CDI); Prod’hom et al (1994) found a higher incidence of late-onset pneumonia in mechanically-ventilated patients who receive antacid (16%) or ranitidine (21%), compared with sucralfate (5%), for SUP; patients taking sucralfate also had a lower gastric pH and less frequent gastric colonization; Herzig et al (2009) noted a 30% increased risk for pneumonia in non-ICU patients who receive antacid therapy; Grindlinger et al (2016) noted incidence of ≈10 ventilator-associated pneumonias (VAPs) per 1000 ventilator days in patients who receive a PPI or H2RA vs 3 VAPs per 1000 ventilator days in patients who receive sucralfate; Dial et al (2004) concluded that development of CDI in hospitalized patients receiving antibiotics was significantly associated with use of PPIs (odds ratio 2); Asseri et al (2008) found that the odds of developing CDI increased by 3.6-fold with PPI use

Enteral nutrition: enteral nutrition (EN) may buffer acid, protect mucosal cells, and improve mucosal blood flow and immunity; results from a meta-analysis by Marik et al (2010) showed that, compared with placebo, H2RAs decreased risk for GI bleeding only in patients not receiving EN, and pneumonia and mortality rates increased in patients who received EN and treatment with H2RAs; they concluded that SUP is likely not necessary and may increase risks for pneumonia and mortality in patients receiving EN; a retrospective review by Palm et al (2018) revealed a 0.5% incidence of CIB (though slightly higher for patients with TBI) and very low rates of ventilator-associated pneumonia, CDI, and mortality in patients receiving EN without SUP

Choice of SUP agent: trials have shown variable results; Kantorova et al (2004) noted similar rates of bleeding and pneumonia among high-risk patients taking PPIs, H2RAs, sucralfate, or placebo; SUP-ICU trial (Krag et al, 2016) revealed a 2.5% incidence of CIB with PPIs, compared with 4.2% with placebo, with no differences in infections, complications, and mortality; the PEPTIC randomized clinical trial (PEPTIC Investigators et al, 2020) found a rate of CIB of 1.3% with PPIs, compared with 1.8% with H2RAs; there was a trend toward increased mortality with use of PPIs; the study was limited by crossover from H2RAs to PPIs

Management: start with risk assessment; immediately commence resuscitation with blood products and reversal of any coagulopathy; perform endoscopy in high-risk patients to rule out upper GI bleeding; evaluate for differential diagnosis, hemodynamic stability, and other contributing factors; manage persistent or recurrent bleeding with angiography or surgery

Readings

Aseeri M, Schroeder T, Kramer J, et al. Gastric acid suppression by proton pump inhibitors as a risk factor for clostridium difficile-associated diarrhea in hospitalized patients. Am J Gastroenterol. 2008;103(9):2308-13. doi: 10.1111/j.1572-0241.2008.01975.x; Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994;330(6):377-381. doi: 10.1056/NEJM199402103300601; Dial S, Alrasadi K, Manoukian C, et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004;171(1):33-8. doi: 10.1503/cmaj.1040876; Grindlinger GA, Cairo SB, Duperre CB. Pneumonia prevention in intubated patients given sucralfate versus proton-pump inhibitors and/or histamine II receptor blockers. J Surg Res. 2016;206(2):398-404. doi: 10.1016/j.jss.2016.08.028; Herzig SJ, Howell MD, Ngo LH, et al. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301(20):2120-8. doi: 10.1001/jama.2009.722; Kantorova I, Svoboda P, Scheer P, et al. Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepatogastroenterology. 2004;51(57):757-61; Krag M, Perner A, Wetterslev J, et al. Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial. Trials. 2016;17(1):205. doi: 10.1186/s13063-016-1331-3; Marik PE, Zaloga GP. Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med. 2001;29(12):2264-2270; Palm NM, McKinzie B, Ferguson PL, et al. Pharmacologic stress gastropathy prophylaxis may not be necessary in at-risk surgical trauma ICU patients tolerating enteral nutrition. J Intensive Care Med. 2018;33(7):424-429. doi: 10.1177/0885066616678385; 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. 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. 2020;323(7):616-626. doi: 10.1001/jama.2019.22190; Prod’hom G, Leuenberger P, Koerfer J, et al. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med. 1994;120(8):653-62. doi: 10.7326/0003-4819-120-8-199404150-00005; Simons RK, Hoyt DB, Winchell RJ, et al. A risk analysis of stress ulceration after trauma. J Trauma. 1995;39(2):289-93;discussion 293-4. doi: 10.1097/00005373-199508000-00017.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Lewis was recorded at Trauma, Critical Care & Acute Care Surgery 2022, held March 28-30, 2022, in Las Vegas, NV, and presented by the Trauma and Critical Care Foundation. For information about upcoming CME activities from this presenter, please visit trauma-criticalcare.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

ABS Continuous Certification

Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit/s toward the CME [and Self-Assessment] requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

GS700102

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.