A 69-year-old man with Type 2 diabetes mellitus and chronic obstructive pulmonary disease is admitted to the ICU with respiratory compromise related to community-acquired pneumonia (CAP), accompanied by delirium, hyperglycemia, and hypovolemia. He responds well to supportive, noninvasive ventilatory therapy, but develops positive stool occult blood testing during the second day in the ICU. Upon clinical improvement, you transfer him to the general medical floor. What is the best strategy for preventing clinically significant gastrointestinal (GI) bleeding during his hospitalization?
Stress-related mucosal disease (SRMD) refers to superficial erosions or focal ulceration of the proximal gastrointestinal mucosa resulting from physiologic demand in acute illness. Multiple factors contribute to its development, including disruption of the protective mucosal barrier, splanchnic vasculature hypoperfusion, and release of inflammatory mediators.1,2 Increasing severity and number of lesions are associated with the propensity for stress-related mucosal bleeding (SRMB). Based on severity, GI hemorrhage can be defined as occult (detected on chemical testing), overt (grossly evident), or clinically important (overt with compromised hemodynamics or requiring transfusion).3
The majority of clinically significant GI bleeding events occur in critically ill patients. Although more than 75% of patients have endoscopic evidence of SRMD within 24 hours of ICU admission, lesions often resolve spontaneously as patients stabilize, and the average frequency of significant bleeding is only 6%. However, when present, SRMB in ICU patients increases the length of hospitalization, cost, and mortality rates.1,3 By contrast, significant GI bleeding occurs in less than 1% of inpatients without critical illness.4
While preventing clinically important bleeding in hospitalized patients is a crucial objective, current practice reflects significant stress ulcer phophylaxis (SUP) overutilization, with substantial economic impact and potential for harm. One in three patients takes antisecretory therapy (AST) upon admission.5 Additionally, SUP is prescribed in 32% to 54% of general medical inpatients, despite the low risk for SRMB. Importantly, these prophylactic agents are continued on discharge in more than half of these patients.6-9 Clinician prescribing practices potentially can set an unfounded standard of care for obligatory prophylaxis among inpatients.
Data for Clinical Decision-Making
Several studies report the risks for gastrointestinal hemorrhage related to acute illness. In a prospective study of 2,252 ICU patients, two independent predictors of clinically important, new-onset SRMB were identified: mechanical ventilation for more than 48 hours and coagulopathy (see Table 1). Of these risk factors, respiratory failure was present in virtually all patients with GI hemorrhage; only one patient had coagulopathy alone. Mechanical ventilation or coagulopathy was associated with a 4% risk of clinically important GI bleeding, whereas patients with neither symptom had a 0.1% risk.
Though GI bleeding was uncommon, mortality associated with bleeding was 49%, compared with 9% in the nonbleeding group. In the absence of one of these two risk factors, 900 ICU patients would need to be treated to prevent one clinically important GI bleeding event.3 Other studies identify an increased risk of GI bleeding in subsets of patients with trauma, thermal injury, and organ transplantation. Additional possible risk factors might include septic shock, glucocorticoid or NSAID use, renal or hepatic failure, and prior GI bleeding or ulcer.10 The likelihood of GI bleeding increases proportionate to the number of risk factors present.
Limited data for non-ICU patients demonstrate an increased bleeding risk in the presence of ischemic heart disease, chronic renal failure, mechanical ventilation, or prior ICU stay.11 One study of 17,707 general medical patients found a low overall incidence (0.4%) of overt or clinically important GI bleeding, mainly in patients treated with anticoagulants without a mortality difference related to bleeding events.4
The 1999 American Society of Health System Pharmacists (ASHP) Therapeutic Guidelines on Stress Ulcer Prophylaxis reviewed extensive data by level of evidence to identify clinical indicators of patients at higher risk (see Table 2, p. 31).10 The bottom line is that stress-related bleeding depends on the type and severity of illness. Independent risk factors for critically ill patients include mechanical ventilation or coagulopathy. Stable general medical inpatients are at very low risk of clinically significant GI bleeding.
Clinical predictors help define patients at the greatest risk of SRMB. However, to be meaningful, SUP must improve clinical outcomes. Despite extensive studies on the efficacy of pharmacologic agents in the prevention of significant bleeding, several trials do not show a benefit of SUP over placebo, even in patients with major risk factors.4,12,13 Other independent studies and meta-analyses demonstrate that H2-receptor antagonists (H2RAs) prevent ICU bleeding, reducing events by approximately 50%.10 Of all the available prophylactic agents, H2RAs are FDA-approved for this use, proton pump inhibitors (PPIs) are likely as effective, and both are well-tolerated. However, data suggest that the use of AST is associated with C. difficile-associated disease, hip fracture, and pneumonia.
Outside of the ICU, there is no difference in de novo GI bleeding among general medical patients prescribed SUP. The ASHP guidelines thus conclude there is no indication for SUP in stable, general medical inpatients.10
A subset of seriously ill patients has an increased risk for significant SRMB, but ideal prevention is not well-defined. As noted in the ASHP guidelines, “prophylaxis does not necessarily prevent bleeding in patients with documented risk factors, and the efficacy of prophylaxis varies in different patient populations.”
Given the effect of SRMB, it is reasonable to provide preventive agents to subgroups of critically ill patients with significant risk factors of mechanical ventilation for more than 48 hours and underlying coagulopathy. Studies report that judicious SUP prescription when these risks are present reduces cost without increasing morbidity or mortality in the ICU.14
Back to the Case
Our case addresses a patient in both an ICU and general medical setting. Based on his lack of risk factors for significant GI bleeding, SUP was not indicated. In this case, the patient improved. Had he developed ventilatory failure requiring intubation, the risk of clinically important GI bleeding would have approached 4%, and H2RA prophylaxis would have been recommended. Although the optimal length of prophylaxis is unknown, SUP likely can be discontinued on transfer out of the ICU, as clinical stability is associated with a substantially lower risk of clinically important bleeding.
Literature supports the limited use of SUP in hospitalized medical inpatients. SUP can be reserved for critically-ill patients with major risk factors, including prolonged mechanical ventilation or coagulopathy. TH
Dr. Wright is associate professor and head of the section of hospital medicine of the Department of Medicine at the University of Wisconsin School of Medicine and Public Health.
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