Characteristics of non-variceal upper gastrointestinal bleeding and factors related to recurrence at Hanoi medical university hospital, Vietnam – Nguyen Phuc Binh

JMR 116 E3 (7) - 2018 19 JOURNAL OF MEDICAL RESEARCH CHARACTERISTICS OF NON-VARICEAL UPPER GASTROINTES- TINAL BLEEDING AND FACTORS RELATED TO RECURRENCE AT HANOI MEDICAL UNIVERSITY HOSPITAL, VIETNAM Nguyen Phuc Binh1, Dao Viet Hang1,2, Tran Quoc Tien2, Dao Van Long1,2 1Hanoi Medical University Hospital; 2Hanoi Medical University Hospital Upper gastrointestinal bleeding is an emergency requiring immediate management and cooperation of many specialties. Among the causes of upper gastrointestinal bleeding, non-variceal upper gastrointestinal bleeding has the highest percentage. Initial assessment, prognosis factor classification and suitable interven- tions will help to reduce recurrent bleeding rate. The study aims to evaluate the characteristics of non-variceal upper gastrointestinal bleeding and identify correlating factors of recurrent bleeding. A retro- spective descriptive study was conducted on non-variceal upper gastrointestinal bleeding patients admitted to Hanoi Medical University Hospital with ICD 10 code K92.2 from January 2013 to March 2017. There were 444 patients with the mean age of 49.1 (18.1). There were 69.8% of patients with co-morbidities in which 25.9% had history of upper gastrointestinal bleeding. The median Rockall score was 3 and the median Glas- gow-Blatchford Bleeding Score (GBS) was 7. The rate of endoscopic interventions was 48.4% in which 99.1% achieved success. The rate of recurrent bleeding in hospital was 4.5% and within 30 days after dis- charge was 1.1%. There was no difference of recurrence in the groups performed mono and combined therapies. Glasgow-Blatchford Score and Rockall score had low prognosis performance for in-hospital recur- rence. In conclusion, the rate of recurrence both in hospital and within 30 days in non-variceal upper gastro- intestinal bleeding patients was low. Keywords: non-variceal upper gastrointestinal bleeding; epidemiology; recurrent bleeding; related factors I. BACKGROUND Upper gastrointestinal bleeding is one of the most common gastrointestinal emergen- cies which requires urgent assessment and interventions with mortality rate of 2 - 15% [1]. The incidence of upper gastrointestinal bleed- ing ranges from 48 to 172/100.000 adults per year in which men and old people have a higher rate [2 - 4]. Among the etiologies of upper gastrointestinal bleeding, as many pre- vious studies recorded, non-variceal bleedings accounted for the highest percentage. The causes could be various including peptic ulcer, Mallory Weiss, malignancy, vascular malfor- mation and unidentified injuries [1]. Patients with upper gastrointestinal bleeding may de- velop recurrent bleeding in hospital (7 - 16%) or after discharge (8%) [5; 6]. To classify patients based on severity when admission and detect factors that are related to bleeding recurrence is important to follow up and make prognosis [7]. In Vietnam, there have not been many epidemiology studies in non-variceal upper gastrointestinal bleeding. A multi- centered research at 17 major hospitals in Vietnam in 2015 recorded the rate of in- hospital recurrent bleeding in patients with upper gastrointestinal bleeding was 5.7% [8]. Therefore, we decided to conduct our study at Hanoi Medical University Hospital to report Corresponding author: Dao Viet Hang, Hanoi Medical Univesity Email: hangdao.fsh@gmail.com Received: 11/1/2018 Accepted: 08/11/2018 20 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH characteristics, recurrence rate and factors associated to recurrence in non-variceal upper gastrointestinal bleeding patients. II. METHODS The study used a retrospective method with convenient sample size, which was con- ducted at Hanoi Medical University Hospital. Medical records of patients who were admitted to HMUH from January 2013 to March 2017 with diagnosis of upper gastrointestinal bleed- ing according to the criteria of ICD code being K92.2 were collected. Patients with melena and/or hematemesis and endoscopy showing bleeding lesions in the upper GI tract except variceal bleeding were included in the study. We excluded patients who were admitted to HMUH and diagnosed with upper gastrointes- tinal bleeding but discharged immediately without upper endoscopy, further intervention and treatment, patients who did not provide correct addresses and contacts or patients refused to attend in the study. Patients characteristics included demo- graphic information (age, gender), previous upper GI bleeding, comorbid diseases, arrival time, clinical symptoms, hemodynamic status on admission and after upper endoscopy, indi- cation of blood transfusion, gastroscopic diag- nosis, gastroscopic interventions and other treatments during hospital stay. Blood transfu- sion was selected instead of haemoglobin level since all patients with significantly low heamoglobin would receive blood transfusion. Patients’ risks were evaluated by the Glasgow -Blatchford Bleeding Score to assess the need for intervention and the Rockall score (Pre- endoscopic and complete) to predict the risk of recurrent bleeding and mortality. Recurrent bleeding was diagnosed with symptoms of repeated hematemesis or black stools, a drop of Hemoglobin ≥ 2g/dl or changes of hemodynamic status after control- ling bleeding or having yellow stool. Cases of in-hospital recurrent bleeding were taken from medical records, cases of recurrent bleeding within 30 days after discharge were collected from contacting patients or patient’s family members by phone numbers. We analyzed and demonstrated data by using R program. Statistical analysis included t -test, Mann – Whitney test for categorical vari- ables and Chi-square test, Fisher test for quantitative variables. Logistic regression was used for evaluating the association of recur- rent bleeding and related factors. Recurrent bleeding’s predictive value of different scores was demonstrated by the area under the curve (AUC). A P-value of less than 0.05 was con- sidered significant. III. RESULTS 1. Demographic characteristics Our study recorded 444 cases of non- variceal upper gastrointestinal bleeding, among those 67.3% was male. The average age (SD) was 49.1 (18. 08), with the eldest patient being 91 years old and the youngest being 10. 2. History Based on medical records, 69.8% of cases had at least one comorbid disease which con- sisted of cardiovascular diseases, diabetes, musculoskeletal diseases and liver diseases. 25.9% had a past history of upper gastrointes- tinal bleeding. 9.23% used non-steroidal anti- inflammatory drugs (NSAID) and/or coagula- tion before admission. JMR 116 E3 (7) - 2018 21 JOURNAL OF MEDICAL RESEARCH Symptoms, Glasgow-Blatchford Score and Rockall score Symptoms: Black stool was the most com- mon symptom (83.8%). Other symptoms recorded were hematemesis (32.43%), ab- dominal pain (44.14%) and fatigue (6.08%). Vital signs on admission: The mean heart rate was 91.9 (18.1) beats/min. There was 25.7% of patients had tachycardia (heartbeat > 100 beats/min). 8.6% of the patients had low blood pressure (defined as systolic pressure lower than 90 mmHg or diastolic pressure lower than 60 mmHg). Glasgow-Blatchford Score and Rockall score: To stratify risk, the Glasgow-Blatchford Score and the Rockall score (both pre-endos copy and complete) were used. As a result, a median score of Glasgow-Blatchford Score was 7 (4 - 10) and 63.0% of cases had Glas- gow-Blatchford Score ≥ 6. About the Rockall score, a median Rockall score was 3 (1 - 5) with 71.2% in the high-risk group (Rockall score > 3). Pre-endoscopy Rockall score re- ported low percentage (57.4%) in the high-risk group and the median score was 1 (0- 2). Table 1. Risk Score of upper gastrointestinal bleeding Upper endoscopy findings and interventions Time of endoscopy: 93,5% of cases received endoscopy within 24 hours of admission in which 34.7% had endoscopy before admission (outpatient indication before admission). The duration- from hospital admission to upper endoscopy had a median value of 4 (2.5 - 11) hours. Bleeding etiologies: Table 2 presents the causes of non-variceal upper gastrointestinal bleed- ing, which duodenal bulb ulcer and gastric ulcer were predominant causes (63.5% and 23.2%), respectively. In total, 33.78% of patients had active bleeding at the site of lesions. Among 387 patients with bleeding ulcers, 61.5% was in high-risk stigmata group (rebleeding rate from 22- 55%) (Table 3). Rockall score (Complete) (Median (Interquantile)) 3 (2 - 5) < 3 points (low risk group) 26,1% 3 - 8 points (moderate risk group) 73,3% > 8 points (high risk group) 0,6% Glasgow-Blatchford Score (Median (Interquantile)) 7 (4 - 10) Glasgow-Blatchford Score < 6 37,0% Glasgow-Blatchford Score ≥ 6 (50% of patients need intervention) 63,0% 22 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH Table 3. Characteristics of peptic ulcers Forrest Classification Patients with ulcers (n = 387) High-risk stigmata group Forrest IA (Spurting bleeding) 9/387 (2.3%) Forrest IB (Oozing bleeding) 109/387 (28.2%) Forrest IIA (Non-bleeding visible vessel) 62/387 (16%) Forrest IIB (Adherent clot) 59/387 (15.2%) Low-risk stigmata group Forrest IIC (Flat spot) 20/387 (5.2%) Forrest III (Clean base) 128/387 (33.1%) Endoscopy interventions: Almost half of the cases of non-variceal upper gastrointestinal bleed- ing required endoscopic intervention (48.4%) with the successful rate of 99.1%. 2 patients failed interventions due to restlessness. Nearly 70% of the intervened patients required only mono ther- apy - epinephrine injection (69.77%). The second most common method was the combination of epinephrine injection and endoscopic clips. Other mono the rapies such as endoscopic clips, APC or combination methods only accounted for a small percentage with less than 10%. After interven- tion, there was a significant decrease of heartbeats before endoscopy and after endoscopy (p < 0.001). In the group with hypotension before endoscopy interventions, there was a significant increase in the mean of heart pressure (p < 0.001) Table 2. Causes of non-variceal upper gastrointestinal bleeding Esophagus Esophageal ulcer 8/444 (1.8%) Mallory Weiss 25/444 (5.6%) Stomach Gastric ulcer 103/444 (23.2%) Dieulafoy lesion 8/444 (1.8%) Malignancy 16/444 (3.6%) Duodenum Duodenal bulb ulcer 282/444 (63.7%) Anastomosis ulcer 15/444 (3.4%) Unidentified injury 26/444 (5.9%) JMR 116 E3 (7) - 2018 23 JOURNAL OF MEDICAL RESEARCH Table 4. Changes of vital signs after endoscopic intervention Pre-endoscopy Post-endoscopy p Heart rate (beats/min) 94.0 (19.2) 88.2 (11.7) < 0.001* MAP in pre-endoscopy hypotension group (mmHg) 62.4 (9.0) 81.2 (10.3) < 0.001* MAP: Mean arterial pressure; *: Statistically significant Recurrent bleeding rate and related factors There were 20 cases (4.5%) who had recurrent bleeding during hospital stay. There was no difference in recurrent bleeding rate between intervention group and non-intervention group (p = 0.755). In the intervention group, the difference of in-hospital bleeding rates between mono therapy and combined therapies groups was not statistically significant (p = 0.088). Among 272 contacted patients by phone number, there were only 3 patients (1.1%) who had recurrent bleed- ing within 30 days after discharge. Table 5. In-hospital recurrent bleeding and related factors Factors Recurrent bleeding Univariate logistic regression Multivariate logistic regression Yes (20) No (424) OR (95% CI) p OR (95% CI) P Demographic Age ≤ 60 > 60 16 4 302 122 0.62 (0.20, 1.89) 0.395 Gender Female Male 2 18 143 281 4.58 (1.05, 20.01) 0.027* 5.60 (1.27, 24.76) 0.023* Patient’s medical history Comorbid diseases No Yes 3 17 131 293 2.53 (0.73, 8.79) 0.13 Past history of UGIB No Yes 13 7 316 108 1.58 (0.61, 4.05) 0.342 24 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH Factors Recurrent bleeding Univariate logistic regression Multivariate logistic regression Yes (20) No (424) OR (95% CI) p OR (95% CI) P Hemodynamic status Tachycardia Heartbeat < 100 Heartbeat > 100 15 5 314 110 0.95 (0.34, 2.68) 0.925 Low blood pressure No Yes 16 4 390 34 2.87 (0.91, 9.06) 0.061 Endoscopy Intervention No intervention 10 219 Singular intervention 6 210 0.63 (0.22, 1.75) 0.368 Combined intervention 4 35 2.50 (0.74, 8.42) 0.127 Red blood cell transfusion in hospital No Yes 6 14 272 152 4.18 (1.57, 11.09) 0.002* 4.83 (1.80, 12.94) 0.002* Risk score Rockall score (complete) < 3 ≥ 3 5 15 120 295 1.22 (0.43, 3.43) 0.705 GBS ≤ 6 > 6 6 14 158 253 1.46 (0.55, 3.87) 0.448 * GBS: Glasgow-Blatchford Bleeding Score; OR: Odds ratio; CI: Confidence interval; *: Statistically significant By using univariate logistic regression, only gender and red blood cell transfusion had an asso- ciation with recurrent bleeding. Specifically, the odd of having recurrent bleeding in male was 4.58 times higher than female (95% CI: 1.05 - 20.01; p = 0.027) and patients who were required red blood cell transfusion also had a higher odd of recurrent bleeding (OR = 4.18 (1.57, 11.09)). A JMR 116 E3 (7) - 2018 25 JOURNAL OF MEDICAL RESEARCH similar result was shown in multivariate regression when gender and blood transfusion remain associated with recurrent bleeding. ROC curves analysis showed the prognosis ofthe Glasgow-Blatchford Score, the Pre- endoscopic and Complete Rockall score. All three scores demonstrated limitations in predicting in -hospital bleeding (Figure 1). Figure 1. ROC curves of Glasgow-Blatchford Score, Pre-endoscopic and Complete Rockall score in predicting in-hospital recurrent bleeding IV. DISCUSSION In our study, we reported the high rate of endoscopy performance within 24 hours after admission (93.47%) with a median time of 4 hours. This rate was higher compared to the multi-centered research at 17 major hospital in 2017 by Long et al which reported only 71.8% with a longer median time (14.5 hours) [8]. It demonstrated the quick approach protocol in upper gastrointestinal bleeding in HMU hospi- tal and showed the efficacy of on-call bleeding control team. According to our findings, the proportion of in-hospital recurrent bleeding was 4.5% and the proportion of recurrent bleeding within 30 days was only 1.1%. These results were lower than other researches in Asia and South-East Asia countries such as Iran (16.7%), Hong Kong (8.8%), Thailand (7.8%) and similar to another research in Vietnam (5.7%) [7 - 10]. This could be explained by difference of geo- graphic studies. Moreover, in our study, the percentage of patients requiring interventions, especially combined endoscopic intervention was lower than other foreign studies. 26 JMR 116 E3 (7) - 2018 JOURNAL OF MEDICAL RESEARCH After endoscopic interventions, significant changes of patient’s vital signs were recorded, especially in patients with admission hypoten- sion, which could be evaluated as the efficacy parameter of endoscopic interventions. When evaluating factors possibly relating to recurrent bleeding, only gender and blood transfusion were associated with recurrent bleeding. There was no association between recurrent bleeding and age groups, patient’s history, hemodynamic status, types of inter- vention and risk scores. It could be explained that the number of patients with recurrent bleeding was small in our study. The utility of risk score such as the Glasgow-Blatchford Score and the Rockall score (pre-endoscopic and complete) was mentioned in many re- search and was recommended in the guideline of European Society for Gastrointestinal Endo- scopy (ESGE) [1; 11; 12]. However, in our study, both scores showed poor predictive value on ROC curves. The reason might be due to the small number of recurrences in our study. However, it should be noted that our study had some limitations. Because our study method was retrospective cohort research, data were mostly collected from medical re- cords, there fore, some data were not suffi- cient to be analyzed and sample selection could not be randomized. Contacting patients to identify their history of recurrent bleeding could be affected by recall bias. V. CONCLUSION Almost all (95.3%) patients received endo- scopy within 24 hours. 48.4% of endoscopy patients were performed at least one endo- scopic intervention and success rate was 99.1%. 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