ABSTRACT: Gastrointestinal bleeds (GIBs) are a significant source of hospitalizations in the United States. GIBs are categorized into two types: upper GI bleeds and lower GI bleeds. Each type can present with different hallmark presentations and require different management. Upper GIB is dependent on endoscopic therapy and may benefit from various pharmacologic treatments in specific scenarios, such as proton pump inhibitors and macrolides. Management of lower GIB is focused on colonoscopy and mechanically treating bleeds, with little pharmacological intervention. Pharmacists can provide effective service to these patients at multiple points of patient care.
Gastrointestinal bleeding (GIB) is a relatively common medical issue, causing a significant portion of morbidity, hospitalizations, and even mortality annually in the United States. The raw estimated rate of hospitalization secondary to any type of GIB in the U.S. is estimated to be about 375 per 100,000 per year.1-3 For acute GIB events, some studies identify a 30-day mortality rate as high as 14%, while others report a range between 6% and 10% per year, with rates increasing in patients with advancing age and a higher number of associated underlying comorbidities.4-7 It is estimated that more than $2.5 billion is spent annually to care for inpatient management of GIB.8
Given the nature of GIB, it is important to differentiate the disease state, as location of the bleed can dictate both presentation and treatment (TABLES 1-3). Historically, distinction of upper GIB (UGIB)and lower GIB (LGIB) was based on the location of bleeding in relation to the ligament of Treitz.9,10 With this definition, bleeding proximal to the ligament of Treitz is categorized as an UGIB, while bleeding distal to the ligament of Treitz is categorized as a LGIB. While other definitions do exist in some literature, this definition is generally established in most practice.11,12
Initial Presentation and Risk Stratification
At presentation, workup of any suspected GIB is initially similar, wherever the origin of the bleed. Immediate evaluation should focus on the patient’s hemodynamic stability. This priority has been well established in other hemorrhagic models and remains true in cases of GIB.16-18 Physical assessment of blood pressure, heart rate, and orthostatic status should be performed, and resuscitation provided as appropriate. This resuscitation should begin with intravenous fluids but may also require transfusions of packed red blood cells.
Additional assessment of patients presenting with GIB should include a focused patient history aimed at identifying the nature, duration, and potential source of the bleeding, as well as laboratory testing (CBC, BMP, coagulation studies).17,18 When evaluating these patients from a pharmacist perspective, it is important to note any current or recent medication use that may increase the risk of bleeding, including agents such as nonsteroidal anti-inflammatory drugs, antiplatelet agents, and/or anticoagulants. Early identification of these factors may help expedite both diagnosis and appropriate treatment response.
Risk assessment and stratification is clinically useful to help distinguish patients at high and low risk of adverse outcomes.17,18 In stratifying patients into evaluated risk groups, initial informed decision-making can be made. Specifically, stratification may provide insight into factors such as timing of endoscopy or colonoscopy, necessary level of care, and timing of discharge. Various established tools are available to aid in the assessment of individual risk.
For patients with acute UGIB, there are several clinical prediction tools that have been developed, including two well-evaluated tools cited in evidence-based guidelines: the Blatchford score (TABLE 4) and the Rockall score (TABLE 5).17-20 The Rockall score utilizes clinical data immediately at presentation.19 Factors assessing the severity of the bleed, such as systolic blood pressure and heart rate, are assessed alongside patient characteristics, such as age and comorbid conditions, resulting in a tool to assess prognostic outcomes and potentially mortality. Similarly, the Blatchford score uses both clinical and laboratory data to assist in predicting risk of intervention and mortality.20 For acute LGIB, the available prognostic rules to assess risk are limited and less validated when compared with UGIB.22
Upper GI Bleed Pharmacotherapy
Proton pump inhibitors (PPIs) are the drug class most associated with treatment of UGIB. In an UGIB patient, gastric acid can inhibit platelet aggregation and weaken potential coagulation, leading to an impairment in bleeding cessation. To inhibit this process, inhibition of gastric acid secretion intended to raise stomach pH to 6 or higher can help stabilize clots and improve clinical outcomes.24
PPIs are unique in that they have potential application both pre- and postendoscopy. In the setting of pre-endoscopy, guidelines do not form consensus on their use, but they may decrease proportion of patients with high risk of stigmata of hemorrhage at the time of the procedure.25 Despite potential benefit in this population, evidence suggests PPI use does not affect rebleeding, necessary surgery, or mortality, leading to some clinical controversy regarding their application. However, patients for whom endoscopy cannot be performed or will be delayed have demonstrated a potential decrease in risk of rebleeding through utilization of PPI. Evidence suggests PPIs decrease incidence of high-risk stigmata of hemorrhage at time of endoscopy but do not affect rebleeding, necessary surgery, or mortality.17,26 Postendoscopic therapy, PPIs can be used both acutely and chronically.17
Continuous Infusion Versus Intermittent PPI
Appropriate dosing and administration of PPI have been evaluated closely in recent years (TABLE 6). A bolus IV dose followed by infusion was long the normal course of therapy and remains the treatment of choice in currently available guidelines, but data suggest that twice-daily IV bolus dosing is noninferior in outcomes of rebleeding, mortality, and length of hospital stay.17,27 Recent literature has demonstrated that intermittent PPI use was noninferior and offers a clear benefit in drug dose, cost, and resource utilization. The authors suggest the that guidelines be updated to recommend intermittent PPI therapy in endoscopically treated GIB.27 In practice, many institutions now favor intermittent dosing in order to decrease resource use and overall cost.
Intravenous PPI Versus Intravenous H2 Antagonists
Considering H2 antagonists (H2As) are used with similar intent in other disease states, their use in UGIB has been investigated alongside PPIs. A 2015 meta-analysis evaluating the two classes in the setting of UGIB found that while difference in mortality was found to be nonsignificant, outcomes such as recurrent bleeding rate and receiving surgery rate displayed clear benefit in PPIs. This deficit is likely due to H2As’ inferiority at maintaining gastric pH over 6.0, the approximate pH where coagulation processes can function.29
In effort to improve visualization during endoscopy and thus decrease need for repeat endoscopy, IV erythromycin, an antimicrobial macrolide that also acts as a prokinetic agent, is commonly utilized. A single dose of 250 mg or 3 mg/kg is generally well tolerated.17,30 A 2016 meta-analysis concluded erythromycin use prior to endoscopy significantly decreased the need for second-look endoscopy and length of hospital stay, and thus it carries a recommendation to be used in the European Society of Gastrointestinal Endoscopy guidelines.30,31
It is fair to wonder if possible benefit is a class effect or specific to erythromycin. Azithromycin, a generally more commonly utilized macrolide, has been evaluated and appears to be a noninferior alternative to erythromycin. Azithromycin may carry some logistical advantages, such as not requiring reconstitution and generally greater availability due to its use in empiric pneumonia treatment.32
H pylori Treatment
Patients diagnosed with bleeding associated with Helicobacter pylori infection should be treated via guideline-based eradication therapy, with a goal of complete infection resolution.17 Available literature indicates that eradication of H pylori is significantly more effective than antisecretory treatment alone in patients with UGIB. The first-line regimens for H pylori eradication are detailed in TABLE 7 based on the American College of Gastroenterology’s guidelines on the management of H pylori infection.33 Once the infection is resolved, this group of patients typically does not need to receive maintenance antisecretory therapy unless they require nonsteroidal anti-inflammatory drugs or antithrombotic therapy, with which long-term antisecretory therapy is necessary, as their use can significantly increase the risk of rebleeding.17,18
Lower GI Bleed
After the initial assessment and risk stratification and once the patient is hemodynamically stable, colonoscopy preceded by colon cleansing is the initial diagnostic procedure for most patients presenting with a LGIB.21 Management of LGIB mostly includes nonpharmacologic interventions; however, there are still opportunities for pharmacists to be involved in patient care.
PPI Application in LGIB
Unlike UGIB, available literature evaluating PPI use in LGIB does not show benefit. Trials evaluating UGIB and LGIB have demonstrated that while PPIs do not demonstrate improved outcomes in LGIB, they may actually increase risk of LGIB.34 Theorized mechanisms for this increased risk often focus on possible changes in microbiota, and thus may potentiate possible risk from NSAIDs. These outcomes have proved controversial; however, they offer evidence that patients with LGIB do not benefit from PPI therapy. This potential risk should be carefully assessed in patients, particularly those at risk for UGIB, as careful risk versus benefit may need to be assessed.34
Pharmacists of many specialties are in a unique position to assist in the treatment and management of GIB patients. Outpatient pharmacists are in a prime position to proactively watch for potential risk factors in patients, including high-dose NSAIDs and anticoagulants, and reduce the chance of GIB at the front line. Additionally, they can provide important counseling and dose optimization for patients both prior to and subsequent to a GIB diagnosis. Similarly, inpatient clinical pharmacists can also have a large role in GIB treatment. They may be in a position to assist in multiple areas during the initial evaluation and management. Initial medication reconciliation may reveal details relevant to diagnosis and treatment of patients, such as identifying outpatient NSAID or anticoagulant use. Pharmacists can also provide recommendations to the healthcare team regarding which medications may provide benefit to each GIB case.
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