Management of Non-Variceal Upper Gastrointestinal Bleeding

Hemodynamic resuscitation and transfusion strategy

Evidence suggests that excessive transfusion may lead to increased visceral blood flow and pressure, thereby destabilizing existing blood clots and increasing the risk of rebleeding and mortality [3,4]. Thus, a restrictive red blood cell transfusion policy is strongly advocated by international guidelines. The standard approach recommends transfusion when hemoglobin falls below the restrictive threshold of 7 g/dL for hemodynamically stable patients without a history of cardiovascular disease, aiming for a post-transfusion target of 7–9 g/dL. Conversely, a more liberal strategy is recommended for patients with a history of acute or chronic cardiovascular disease, utilizing a threshold of ≤8 g/dL and targeting a concentration of ≥10 g/dL to mitigate the risk of cardiac ischemia and decompensation (Table 1) [4-6].

Table 1.

Transfusion thresholds and targets for patients with gastrointestinal bleeding

Patient risk stratification

The Glasgow-Blatchford Score (GBS) is the preferred clinical tool for pre-endoscopy risk stratification, predicting the need for intervention (transfusion, endoscopic therapy, or surgery) based on clinical and laboratory parameters, without requiring endoscopic findings (Table 2) [3]. The primary clinical utility of the GBS is to identify a cohort of very-low-risk patients, specifically those with a score of ≤1. These patients have a negligible risk (≤1%) of requiring intervention or experiencing death within 30 days and may, therefore, be safely managed as outpatients with elective follow-up endoscopy, optimizing resource utilization [7]. However, current scoring models, including the GBS, suffer from low specificity, often leading to the unnecessary hospitalization of many patients who ultimately do not require intervention, highlighting an area for improvement in future prognostic models [3].

Table 2.

Glasgow-Blatchford Score

Pre-endoscopy pharmacological therapy (PPI)

The pre-endoscopy use of high-dose intravenous PPI therapy is intended to reduce the prevalence of high-risk endoscopic stigmata by potently suppressing gastric acid secretion. Thus increases the intragastric pH to ≥6, which facilitates clot stability and reduces pepsin-induced clot lysis [8]. Although this mechanism is supported by clinical trials showing a modest reduction in the subsequent need for endoscopic hemostasis, the evidence regarding improvement in major clinical outcomes, such as rebleeding or mortality, remains inconclusive. Consequently, the recommendation for pre-endoscopic PPI use varies significantly across major guidelines (Table 3) [3-5]. Irrespective of regional variations, the paramount consensus among all international bodies is that the administration of PPI must never delay definitive diagnostic and therapeutic endoscopy [3,9].

Table 3.

Comparison of pre-endoscopy PPI recommendations by guidelines

Recent clinical trials comparing pre-endoscopic oral potassium-competitive acid blockers (P-CABs) with intravenous PPI boluses have indicated that P-CABs may be more effective. Studies have shown that patients receiving P-CABs have a lower proportion of high-risk lesions (Forrest IIa or higher) and a reduced need for therapeutic intervention, likely because of the faster peak concentration (within 1 hour) and greater acid stability [10].

In terms of adjunctive measures, an infusion of erythromycin (up to 250 mg infused 30–120 minutes prior to endoscopy) is suggested to act as a prokinetic agent to improve visualization in clinically severe ongoing active NVUGIB. However, it is worth noting that its clinical use is currently difficult in Korea due to accessibility issues [11]. Conversely, the routine use of tranexamic acid is strongly discouraged due to the lack of proven benefits and the potential for increased risk of thromboembolic events [12]. Furthermore, routine nasogastric or oro-gastric aspiration/lavage is not recommended, and prophylactic endotracheal intubation should be reserved only for selected high-risk patients (e.g., those with ongoing active hematemesis, agitation, or encephalopathy) rather than being performed routinely [13].

Management of antiplatelet and anticoagulant agents

Managing anti-thrombotic therapy requires balancing between the risk of rebleeding and the substantial risk of potentially fatal thromboembolic events. For low-dose aspirin (ASA) used for secondary cardiovascular prophylaxis, the agent should not be interrupted. If interrupted for any reason, it should be restarted as soon as possible, preferably within 3–5 days [14]. For patients receiving dual antiplatelet therapy (DAPT), ASA should be maintained, while the second antiplatelet agent may be interrupted but must be restarted quickly, preferably within 5 days, following cardiology consultation. Regarding anticoagulation therapy (vitamin K antagonists and direct oral anticoagulant), these agents should be withheld upon presentation but must be resumed as soon as bleeding has been controlled, preferably within or soon after 7 days, based on the patient’s thromboembolic risk [15]. Prophylactic PPI co-therapy is recommended for patients requiring ongoing DAPT or anticoagulation with a history of NVUGIB to prevent future bleeding episodes.

Timing of endoscopy

Following adequate hemodynamic resuscitation, early endoscopy (≤24 hours) is strongly recommended for all admitted NVUGIB patients. Evidence strongly discourages the routine performance of urgent endoscopy (≤12 hours), as large-scale studies have failed to demonstrate improved patient outcomes compared to the 24-hour window, and emergent endoscopy (≤6 hours) may even be associated with worse patient outcomes by delaying critical resuscitation efforts [16,17]. While patient stabilization must always precede endoscopy, urgent endoscopy within 12 hours may be considered only for patients with persistent hemodynamic instability after adequate resuscitation efforts have been made.

Endoscopic diagnosis and hemostasis

The Forrest classification is essential for standardizing peptic ulcer stigmata and determining the need for intervention. Active bleeding (Forrest Ia, Ib) and ulcers with a non-bleeding visible vessel (Forrest IIa) are classified as high-risk stigmata and mandate endoscopic hemostasis [18,19]. The preferred hemostasis technique for active bleeding (Ia, Ib) is combination therapy, typically pairing epinephrine injection with a second thermal (e.g., bipolar electrocoagulation, heater probe) or mechanical modality (clips), as epinephrine monotherapy is considered less effective and is not recommended [20].

The management of ulcers presenting with an adherent clot (Forrest IIb) remains contentious. While the American College of Gastroenterology (ACG) panel has made no recommendation for or against endoscopic therapy, the European Society of Gastrointestinal Endoscopy (ESGE) suggests that clot removal may be considered, with hemostasis then applied to any underlying high-risk stigmata. For selected active ulcers characterized by large size (≥2 cm) or high-risk location, the use of a cap-mounted clip (e.g., over-the-scope clip [OTSC]) may be considered. However, it should be noted that the use of OTSC in Korea is currently restricted, as it is not covered by the national health insurance. Endoscopic hemostasis is also recommended and is considered effective for controlling hemorrhage caused by Dieulafoy’s lesions or active bleeding from Mallory–Weiss syndrome [21,22].

In cases of persistent bleeding refractory to standard hemostatic modalities, the application of a topical hemostatic spray/powder or cap-mounted clip should be considered as a salvage option.

Post-endoscopy pharmacological therapy

High-dose PPI therapy is strongly recommended for 72 hours following successful endoscopic hemostasis or for Forrest IIb ulcers not treated endoscopically, serving to stabilize the clot and prevent rebleeding [18]. This can be achieved either through a continuous intravenous infusion regimen (80 mg bolus followed by 8 mg/h infusion) or by using high-dose intermittent oral or intravenous dosing, which has been shown to be comparable in efficacy. Following the initial 3-day high-dose therapy, high-risk patients were advised to continue oral PPI therapy twice daily for an additional 2 weeks to promote comprehensive ulcer healing and reduce the risk of rebleeding [23].

Recent studies have expanded the role of P-CABs in postendoscopic management. Multicenter randomized trials have confirmed that oral P-CABs are non-inferior to high-dose PPI infusion in preventing 30-day rebleeding [24]. More notably, PCABs showed a statistical advantage in reducing early rebleeding rates at 3 and 7 days, likely due to their ability to achieve and sustain the target intragastric pH more rapidly and reliably than PPIs.

Management also includes H. pylori eradication, which is essential for preventing ulcer recurrence. Owing to the high rate of false-negative results during acute bleeding, if the initial test is negative, it is recommended to repeat the H. pylori test only after the patient has discontinued PPI therapy for a sufficient period to ensure diagnostic accuracy, rather than simply repeating it while still on medication. Furthermore, if the infection is confirmed and treatment is administered, it should be followed by documentation of successful eradication [25,26]. Finally, routine second-look endoscopy is not recommended [27].

Recurrent and refractory bleeding

If clinical signs of recurrent bleeding emerge, the initial recourse is always to attempt to repeat upper endoscopy to achieve hemostasis. The use of cap-mounted clips has been specifically suggested for recurrent PUB. In the pharmacological management of refractory cases that fail to respond to standard PPI therapy, P-CABs serve as a potent rescue option because of their ability to provide rapid, meal-independent, and reliable acid inhibition. If bleeding persists or endoscopic attempts fail, transcatheter arterial embolization (TAE) is suggested as the preferred next step, prioritized over immediate surgery [28]. Surgical treatment is reserved as the final option and indicated only when recurrent or persistent bleeding remains refractory to endoscopic hemostasis and TAE [29,30].

Fig. 1 provides a systematic summary of multidisciplinary management pathways for NVUGIB. This algorithm integrates triage, resuscitation, and targeted interventions into a structured framework, based on the clinical evidence discussed in the preceding sections.

Fig. 1.

Algorithm of management of non-variceal upper gastrointestinal bleeding. GBS, Glasgow-Blatchford Score; RBC, red blood cell; CVD, chronic cardiovascular disease; IV, intravenous; PPI, proton pump inhibitor; OTSC, over-the-scope clip; TAE, transcatheter arterial embolization.