Role of Urgent Endoscopy in Patients With Suspected Upper Gastrointestinal Bleeding

The optimal timing of endoscopy in patients with acute upper gastrointestinal bleeding (UGIB) remains controversial. In this study, we investigated the clinical outcomes of urgent endoscopy in patients with symptoms suggestive of UGIB compared with elective endoscopy. From January 2016 to December 2018, consecutive patients who visited the emergency department and underwent endoscopy for clinical manifestations of acute UGIB were eligible. Urgent endoscopy (within 6 hours) and elective endoscopy (after 6 hours) were dened as the time taken to perform endoscopy from presentation to the emergency department. The primary outcome was mortality rate within 30 days. A total of 572 patients were included in the analysis. Urgent endoscopy was performed in 490 patient. The 30–day mortality rate did not differ between the urgent endoscopy group and the elective endoscopy group. There was no difference regarding the recurrent bleeding rate, total amount of transfusion, and length of hospital stay in both groups. In multivariate analysis, age and the amount of transfusion were factors associated with mortality. Urgent endoscopy was not associated with lower 30–day mortality rate compared with elective endoscopy in patients with suspected of acute UGIB. 6 hours after gastroenterologic consultation) group than in the early endoscopy (within 24 hours) group 7 . In the present study, we found that the proportion of patients who underwent endoscopic treatment was higher in the urgent group than in the elective group, and the need for endoscopic treatment was not associated with reduced recurrent bleeding. These results suggest that initial hemodynamic resuscitation and proton pump inhibitor therapy are more benecial than earlier endoscopy within 6 hours when it comes to improving clinical outcomes 19 .


Introduction
Acute upper gastrointestinal bleeding (UGIB) is one of the most common gastrointestinal emergencies.
Despite remarkable advancements in endoscopic treatments and substantial attempts in reducing mortality, the overall in-hospital mortality rate associated with UGIB is still estimated to be 10% 1 .
Endoscopic examination plays pivotal role in both diagnosis and treatment of UGIB 2 . Current guidelines recommend perform endoscopy within 24 hours of patient presentation, while emphasizing hemodynamic stabilization before the procedure [3][4][5][6] . However, optimal timing of endoscopy within 24 hours and the bene t of earlier endoscopy remains controversial.
Several studies have investigated clinical impact of urgent (within 6 hours of presentation) or early (within 12 hours) endoscopy on mortality in patients with UGIB. Some studies showed no signi cant difference in mortality rate between urgent and elective endoscopy groups in high-risk patients with acute UGIB 7,8 . In contrast, others found that urgent endoscopy was associated with lower mortality rate in highrisk patients with acute non-variceal UGIB 9,10 .
Most of previous studies included highly selected patients with non-variceal UGIB or those with high risk [7][8][9][10][11][12] . However, given that the de nitive diagnosis is made after endoscopic examination, these studies may not re ect real-world clinical practice. Furthermore, it is often challenging to predict the cause of bleeding and to distinguish patients at high risk who require intensive care based on symptoms and information obtained from the emergency room 13 . In this study, we investigated the clinical outcomes of urgent endoscopy in patients with symptoms suggestive of UGIB compared with elective endoscopy.

Methods
From January 2016 to December 2018, 966 consecutive patients who visited the emergency department with symptoms suggestive of UGIB and underwent endoscopy were eligible. Clinical manifestations of acute UGIB included hematemesis, melena, and hematochezia. Of these, 187 patients with no evidence of UGIB on initial endoscopy and 207 patients with a follow-up period of less than 30 days were excluded. Finally, a total of 572 patients were included in the analysis. Patient-related factors (age, sex, comorbidities, previous history of peptic ulcer, and medication history), clinical parameters (presenting symptoms, systolic blood pressure, heart rate, laboratory ndings, amount of transfused red blood cell (RBC), and duration of hospital stay), and procedure-related factors (time to endoscopy, endoscopic diagnosis, and kind of hemostasis) were evaluated using medical records. The GBS was calculated, using systolic blood pressure, heart rate, hemoglobin, blood urea nitrogen, the presence of melena or syncope, and the presence of hepatic disease or cardiac disease 14 .
Patients were divided into two groups according to the timing of endoscopy which was de ned as the time taken to perform endoscopy from presentation: urgent endoscopy group (within 6 hours, n = 490, 85.7%), and elective endoscopy group (after 6 hours, n = 82, 14.3%). Endoscopic treatment was performed using techniques such as thermocoagulation, hemoclip, injection, band ligation, and combination of two or more techniques. The type of treatment was determined by endoscopist. The primary outcome was mortality rate within 30 days. Secondary outcomes included rebleeding rate within 30 days, median duration of hospital stay, and median amount of RBC transfusion.

Ethics information
Approval for accessing patient information was granted from the Institutional Review Board of Gangneung Asan Hospital (2020-03-009). As this retrospective data collection was considered anonymized by the Ethics committee, the need for patient consent was waived by the Institutional Review Board of Gangneung Asan Hospital. The study was conducted according to good clinical and scienti c practices and following the ethical principles of the Declaration of Helsinki.

Characteristics of study population
The baseline characteristics of the study population are summarized in Table 1. Median age of 572 patients was 63 years (range, 19-95 years) and 64.0% were male. More than 80% of the patients had comorbidities, including diabetes mellitus, cerebrovascular accident, chronic kidney disease, and liver cirrhosis. The proportion of patients who were taking antithrombotic agent at the time of admission was 23.8%, and 25 patients (4.4%) were on dual antiplatelet therapy. patients, which was successful in 334 patients. Two patients with duodenal ulcers required trans-arterial embolization after failed endoscopic treatment. One patient who had gastric gastrointestinal stromal tumor underwent surgery, and the remaining patient with duodenal ulcer had conservative management after con rmation of the absence of contrast extravasation on computed tomography scan with angiography. In one patient, duodenal varix was found at endoscopic examination and embolization was performed immediately as the rst-line treatment. Mortality rate within 30 days was 5.4% in total (31/572), 5.3% (26/490) in the urgent endoscopy group and 6.1% (5/82) in the elective endoscopy group, respectively (p = 0.791) (Fig. 1). In-hospital death occurred in 23 patients; the cause of death was hypovolemic shock associated with uncontrolled bleeding in 4 patients, and hepatic failure in 11 patients. Rebleeding rate was assessed in 571 patients, excluding the patient who underwent embolization immediately after endoscopy. Rebleeding rate within 30 days was 6.0% (34/571) in total, 5.9% (29/489) in the urgent group, and 6.1% (5/82) in the elective group, respectively (p = 1.000). The median duration of hospital stay and amount of transfused RBC did not differ between two groups. Among various clinical characteristics, age and amount of RBC transfusion were factors associated with mortality in univariate analysis (

Discussion
In this study, we compared clinical outcomes of 572 patients suspected of acute UGIB according to the timing of emergency endoscopy. The mortality rate within 30 days and recurrent bleeding rate did not differ between the patients who underwent urgent endoscopy within 6 hours from presentation and those thereafter. Logistic regression analysis also showed that urgent endoscopy was not associated with mortality, while age and the amount of transfusion were factors associated with mortality.
Most guidelines recommend performing endoscopy within 24 hours in patients with acute UGIB 3-6 . Endoscopy performed within 24 hours was associated with reduced length of hospital stay, and delayed endoscopy was associated with higher mortality in patients with UGIB 8,15 . However, previous studies have shown con icting results as to whether the earlier endoscopy within 6 to 12 hours from presentation can offer more bene t for patients with UGIB. A retrospective study of 934 high-risk patients with GBS of ≥ 12 found that endoscopy performed within 13 hours resulted in lower mortality rate and shorter hospital stays than later endoscopy 9 . In addition, a cohort study showed that urgent endoscopy within 6 hours was an independent predictor of lower mortality rate compared with elective endoscopy  hours) in high-risk patients with GBS > 7 10 .
In contrast to these results, a retrospective study of 169 patients with acute non-variceal UGIB revealed no signi cant difference in mortality rate, rebleeding rate, and hospital stays between patients receiving endoscopy within 6 hours and within 24 hours 16 . Similarly, another study showed that early endoscopy within 12 hours was not associated with a lower mortality compared with later endoscopy within 24 hours 17 . In a recent randomized controlled trial, a total of 516 high-risk patients (GBS of ≥ 12) with overt signs of acute UGIB, including variceal bleeding, were randomized to urgent (within 6 hours after gastroenterologic consultation) and early (within hours) endoscopy groups 7 . Of note, some patients were not treated as assigned because of hemodynamic instability or changes in their medical conditions.
There was no signi cant difference between the urgent and early groups in mortality rate (8.9% vs 6.6%, hazard ratio, 1.35; 95% CI, 0.72-2.54) and rebleeding rate (10.9% vs 7.8%, hazard ratio, 1.46; 95% CI, 0.83-2.58). In the present study, we included all patients who presented to emergency room with symptoms suggestive of UGIB regardless of the nal diagnosis. The 30-day mortality rate and rebleeding rates did not differ between the patients who underwent endoscopy within 6 hours and those who underwent endoscopy after 6 hours. These results support recent guidelines that recommends performing endoscopy within 24 hours following hemodynamic resuscitation in patients with UGIB and does not recommend earlier (within 12 hours) endoscopy 4,5 .
Endoscopy performed early in the clinical course was considered useful to triage patients based on the endoscopic ndings. Patients with low risk of recurrent bleeding could be discharged earlier. In addition, early intervention within 24 hours was associated with shorter length of hospital stay 18 . In contrast, some studies suggested that earlier endoscopy may yield more high-risk endoscopic stigmata that would have been resolved with proton pump inhibitor therapy. A previous study showed that more retained blood and more actively bleeding lesions were found in patients who underwent endoscopic examination within 8 hours from presentation compared with those who underwent endoscopy between 8 to 24 hours 8 . Recent randomized trial also showed that patients with active bleeding or visible vessel and those who required endoscopic treatment were more frequently found in the urgent endoscopy (within 6 hours after gastroenterologic consultation) group than in the early endoscopy (within 24 hours) group 7 . In the present study, we found that the proportion of patients who underwent endoscopic treatment was higher in the urgent group than in the elective group, and the need for endoscopic treatment was not associated with reduced recurrent bleeding. These results suggest that initial hemodynamic resuscitation and proton pump inhibitor therapy are more bene cial than earlier endoscopy within 6 hours when it comes to improving clinical outcomes 19 .
Several factors have been reported to be associated with mortality in patients with UGIB, including comorbidities, vital signs, and failed endoscopic treatment 10,20−23 . In the present study, the clinical factors associated mortality were age and RBC transfusion. Previous observational study investigated 186 patients in Korea also showed that age (≥ 65 years) was an independent predictive factor for mortality 20 . Worse outcomes in the elderly might be attributable to tendency to having multiple comorbidities and susceptibility to physiological changes of elderly patients. There were also discrepancies regarding the impact of RBC transfusion on mortality in previous studies 20,21,23 . It may be resulted from differences in demographics of patients and study design, and further studies containing various demographic characteristics are needed to identify clinical factors affecting outcomes of patients with acute UGIB.
There are several limitations in this study. First, this is a retrospective study. Although it is desirable to design randomized control trial, performing such kind of study would be di cult and should consider ethical issue because delay in endoscopic procedure may lead to fatal outcomes. Future prospective study would be bene cial to con rm the limited role of urgent endoscopy. Second, because this is a single-center study, the results may not represent the overall national demographics. Indeed, most endoscopic examination was performed within 6 hours in our center. Since the resources required to emergency procedure are limited, the results of this study cannot be generalized. Another possible limitation of this study is that our study population consists of heterogeneous patients, including gastroesophageal variceal bleeding. However, in a clinical practice, it is often challenging to discriminate patients with variceal bleeding from non-variceal bleeding at the time of presentation, even after thorough history taking. Since the decision whether to perform endoscopy immediately or not is made based on information obtained at the presentation, it was assumed to be reasonable to include all patients suspected as having UGIB to determine the role of urgent endoscopy in real-world.
In conclusion, urgent endoscopy within 6 hours was not signi cantly associated with lower mortality and rebleeding rate. We also found that age and RBC transfusion were the factors related to mortality. Based on these ndings, we suggest performing elective endoscopy after hemodynamic stabilization including restricted transfusion in patients with suspected acute UGIB.

Competing interests
All authors declare no potential con icts of interest regarding this manuscript. Figure 1 Mortality and recurrent bleeding rates within 30 days in study population. (A) Mortality rate did not differ between the urgent (≤6 hours from presentation) and elective (>6 hours from presentation) endoscopy groups, (B) recurrent bleeding rate did not differ between the two groups.