Trends in upper gastrointestinal bleeding management

Abstract

Upper gastrointestinal bleeding (UGIB) can be attributed to either non-variceal or variceal causes. The latter is more aggressive with hemodynamic instability secondary to decompensated cirrhosis and portal hypertension. Non-variceal UGIB (NVUGIB) occurs due to impaired gastroprotective mechanisms attributed to several drugs such as anticoagulants and nonsteroidal anti-inflammatory drugs. Helicobacter pylori infection contributes to the development of peptic ulcer bleeding as well. NVUGIB presentation can be either hemodynamically stable or unstable. During the initial assessment a scoring system including patient-related factors (current cardiac, renal, and liver diseases and hemodynamic and laboratory parameters) is used to determine the patient’s prognosis. The Glasgow Blatchford score has been shown to be the most useful and precise. Those with high-risk NVUGIB require urgent assessment and upper endoscopy to achieve better short-term and long-term outcomes such as less hospitalization, blood transfusion, and surgery.

Key Words: Gastric, Peptic, Non-steroidal anti-inflammatory drugs, Anticoagulants, Melena

Core Tip: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a medical emergency that requires assessment of patient factors, hemodynamic parameters, and laboratory work to determine the patient’s prognosis and treatment. Patients with low-risk NVUGIB are typically discharged quickly, while patients with high-risk NVUGIB may require administration of volume replacement, blood transfusion, and high-dose intravenous proton pump inhibitors. These high-risk patients also require urgent upper endoscopy. Evaluation of the need for anticoagulant and analgesics after discharge is also needed.

INTRODUCTION

Upper gastrointestinal bleeding (UGIB) can occur during hospitalization or from widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs) or direct oral anticoagulants (DOACs)[1]. This editorial is in response to the observational study by Wang et al[2], titled “Clinical characteristics of acute non-varicose upper gastrointestinal bleeding and the effect of endoscopic hemostasis”.

UGIB symptoms include bloody vomitus, coffee ground emesis, and/or melena. Bloody emesis is not associated with high mortality nor severe bleeding, but it is associated with a modestly high rate of rebleeding and the need for hemostatic intervention. A worse outcome is associated with the occurrence of both bloody emesis and melena. A common source of non-variceal UGIB (NVUGIB) is a bleeding gastric ulcer[3]. Interestingly, Wang et al[2] reported no statistically significant difference in the incidence of gastroduodenal bleeding ulcers in the middle-aged patients and elderly patients.

ETIOLOGY

NSAIDs

NSAIDs are historically associated with acute and chronic UGIB. Furthermore, extended use of antithrombotic medications (e.g., aspirin) for prophylaxis and management of cardiovascular disorders contributes to the incidence of lower GIB and UGIB[4]. NSAIDs commonly induce gastroduodenal ulcers[5].

DOACs

DOACs are widely used among the elderly population for management of cerebrovascular ischemia. However, their use is associated with severe acute gastrointestinal bleeding due to peptic gastroduodenal ulcers. There is also a high risk of mortality (11.8% at 30 d). Anemia and low hemoglobin levels are predictive of life-threatening bleeding and death[6]. Physiological stress that may be caused by hospitalization in the intensive care unit is associated with altered hemodynamics and stress gastropathy. UGIB due to a gastroduodenal site bleed was recently reported in several patients with coronavirus disease 2019[7].

Helicobacter pylori

Helicobacter pylori (H. pylori) infection is involved in the pathogenesis and development of atrophic gastritis and development of gastric dysplasia. Notably, Popa et al[8] showed that H. pylori infection is common in actively bleeding gastroduodenal lesions. However, H. pylori was not found to be involved in the pathogenesis of perforated peptic ulcers[9].

Wang et al[2] analyzed the etiological causes in their cohort but did not reference H. pylori-related peptic ulcer bleeding. It is important to understand the impact of H. pylori infection in UGIB. There are unique virulence strains of H. pylori that have been reported geographically which impact disease behavior in peptic ulcers and gastric cancer, including Cytotoxin-associated gene A (Cag A) and vacuolating cytotoxin A (Vac A)[10], duodenal ulcer promoting gene A in duodenal ulcers[11], Vac A and helicobacter outer membrane B in gastric cancer[12-14], and Cag A, east Asian Cag A-specific and western Cag A-specific phosphorylation sites[15]. Wang et al[2] described etiological causes such as patient diet, emotional excitement, and fatigue. These factors were not quantified in their assessment, and they are not considered risk factors of UGIB in the published literature of peptic ulcer disease. Cold ambient weather, an external factor, does not cause NVUGIB but is correlated with variceal GIB[16]. Eight patients (1.5%) in the study by Wang et al[2] had a UGIB etiology of iatrogenic/post-endoscopic intervention. The bleeding in that group of patients behaved differently from the other NVUGIB patients with impaired gastric mucosal protection, and the management and outcome were different in each group.

UGIB risk assessment

Pre-endoscopy assessment is a crucial step upon initial evaluation in the emergency room. This assessment is helpful for the early triage of low-risk UGIB patients to guide them towards safe outpatient management. Of the several available risk scores, the Glasgow Blatchford score is considered of high yield. It is able to discriminate between cases requiring urgent endoscopic intervention (within less than 6 hours) vs those who require early endoscopy (between 6-24 hours)[17-19]. Parameters used to calculate the Glasgow Blatchford score are readily available and include age of the patient, comorbid illnesses (cardiac, renal, and liver diseases), symptoms (syncope, melena), vital signs, and basic blood work parameters (complete blood count, renal profile).

High-risk factors include advanced age and comorbid diseases such as cardiac and renal diseases. These factors are significant predictors of hemorrhagic peptic ulcer lesions[20]. In the elderly population, the clinical risk score includes five variables to accurately assess UGIB risk. They include: Charlson comorbidity Index > 2; Systolic blood pressure < 100 mmHg; Hemoglobin < 100 g/L; Blood urea nitrogen ≥ 6.5 mmol/L; and Albumin < 30 g/L. The optimal cutoff value was ≥ 1, with a sensitivity of 97.37% and specificity was 19.21% for predicting the inability to safely discharge the patient. The area under the receiver operating characteristic curve was 0.806[21].

MANAGEMENT OF UGIB

Role of endoscopy in UGIB

After the UGIB patient is initially stabilized with volume resuscitation to manage hemodynamic instability and/or blood transfusion for low hemoglobin levels (7-8 g/L), lower doses of intravenous proton pump inhibitors are started[19,22]. Low doses of proton pump inhibitors are efficacious in the improvement of short-term and long-term outcomes compared to high doses of proton pump inhibitors[23,24]. Then, upper endoscopy is performed to classify (via Forrest score) and treat the bleeding source[25]. The bleeding source can be identified following the use of a prokinetic such as erythromycin[19,26]. Robust evidence showed that the use of bipolar electrocoagulation and/or ethanol injection can achieve better hemostasis. Performing endoscopy between 6-24 hours is safe and not associated with decreased 30-d mortality[26,27].

PROGNOSIS

Rebleeding risk in UGIB

Severe presentation with hemodynamic shock is a risk factor for recurrent bleeding. Therefore, increased follow-up with another endoscopy procedure is needed[28]. Ito et al[29] reported that there are four independent rebleeding risk factors for patients with gastroduodenal ulcer bleeding, including blood transfusion, albumin < 2.5 g/dL, duodenal ulcer, and diameter of the exposed vessel ≥ 2 mm. The presence of three or four factors are associated with rebleeding rates of 44% and 54%, respectively[29].

FUTURE RESEARCH

A more robust scoring system to predict the outcome of bleeding should be developed. It should be able to outperform the shortfalls of the current predictive scoring models that require blood test measurements which could be subject to variabilities relating to the timing of blood extraction as well as intravenous fluid administration and to the patient’s recall of clinical comorbidity. Furthermore, incorporation of parameters to provide better prediction and knowledge of the patient’s biologic hemostasis (a crucial step in bleeding ulcer control) will benefit future scoring models.

CONCLUSION

NVUGIB is a common medical condition that many medical specialties face due to the common use of several medications, such as NSAIDs and DOACs, which induce peptic ulcer-related bleeding. Initial assessment of UGIB will guide physicians and triage patients toward a better outcome. Early resuscitation, possible blood transfusion, proton pump inhibitor treatment, and endoscopy contribute to successful short-term and long-term outcomes.