Study on the preventive effect of intravenous esomeprazole in the management of nonvarices upper gastrointestinal bleeding.

ABSTRACT: This retrospective study investigated the preventive effect of intravenous esomeprazole (IVEO) in the prevention of nonvarices upper gastrointestinal bleeding (NUGIB).This study enrolled 130 patients with NUGIB and all of them underwent successful endoscopic hemostasis, of which 65 cases received routine management and IVEO (Group A) and the other 65 cases received routine management alone (Group B). The primary outcome (recurrent bleeding rate within 72-hour, 7-day, and 30-day), and secondary outcomes ((all-cause mortality, bleeding-related mortality, blood transfused, hospital stay (day), and incidence of adverse events)) were compared between 2 groups.Patients in the group A showed lower recurrent bleeding rate within 72-hour(P < .05), 7-day (P < .05), and 30-day (P < .05), than that of patients in the group B. However, no significant differences were identified in all-cause mortality(P = .26), bleeding-related mortality (P = .57), blood transfused (P = .33), and hospital stay (P = .74) between 2 groups. In addition, both groups had similar safety profile.This study found that routine management and IVEO was superior to the routine management alone for preventing the recurrent bleeding rate after successful endoscopic hemostasis in patients with NUGIB.

Introduction

Nonvarices upper gastrointestinal bleeding (NUGIB) is one of the most common encountered emergency disorders in daily clinical practice worldwide.[ It is reported that its incidence varies between 50 and 150 cases per 100,000 adults annually.[ Although its therapeutic managements have developed, its morbidity and mortality rate remain substantial.[ It is reported that its 30-day mortality rate ranges from 5% to 10%.[ Thus, the current management of NUGIB aims to stabilize hemodynamic circulation, stop existing bleeding, and prevent its recurrence.[

Endoscopic hemostatic intervention is reported that it cannot only identify high-risk stigmata on ulcers, but also can help control gastrointestinal bleeding to prevent its rebleeding and to decrease its mortality and morbidity.[ However, there are still some patients who suffer from rebleeding accident. Thus, further medication is needed after successful endoscopic hemostasis. Studies suggested that intravenous esomeprazole (IVEO) can help prevent NUGIB. But there is lacking of evidence to support it for the prevention of recurrent bleeding in Chinese patients with NUGIB.[ This retrospective study evaluated the preventive effect of IVEO for the prevention of recurrent bleeding in patients with NUGIB after successful endoscopic surgery.

Methods

Ethical approval

This retrospective study, based on the clinical data, was approved by the local ethics committee (Medical Ethical Committee of Changhai Hospital Affiliated to Navy Medical University). This study waived the requirement of sign informed consent from patients, because it was not risky for the patients.

Patients and study design

We performed this study based on the relevant guidelines and regulations. In this retrospective study, 130 eligible patients with NUGIB treated at Changhai Hospital Affiliated to Navy Medical University in China from June 2016 to May 2018 were included. All those patients achieved successful endoscopic hemostasis and routine management. In addition, among all those patients, 65 cases received IVEO (Group A), while the other 65 cases did not receive it (Group B).

Patients aged between 18 and 75 years old and diagnosed with NUGIB were included in this retrospective study. Moreover, all patients received successful endoscopic hemostasis. Exclusion criteria mainly included the following criteria:

bleeding from multiple ulcers or concomitant upper gastrointestinal sources;

gastrointestinal cancers;

patients had taken IVEO;

active GI bleeding;

advanced renal and liver diseases;

allergy to NUGIB; and

incomplete patient case records.

Intervention schedule

All patients in both groups received successful endoscopic hemostasis and routine management. The routine treatment included monitoring vital signs and circulatory conditions, and replenishing body fluids (established venous channels to replenish blood volume, and applied vasoactive drugs to improve blood perfusion). In addition, patients in the Group A also received IVEO 80 mg (AstraZeneca China, Shanghai, China) as a bolus infusion over 30 minutes. Then, it followed by a continuous intravenous infusion of 8 mg/h over 71.5 hours.

Outcome measurements

The primary outcome was recurrent bleeding rate within 72-hour, 7-day, and 30-day. The secondary outcomes were all-cause mortality, bleeding-related mortality, blood transfused, hospital stay (day), and adverse events (AEs).

Statistical analysis

In this study, we utilized SPSS software (SPSS V.19.0, IBM Corp., Armonk, NY) for statistical analysis. The continuous data was calculated as mean and standard deviation, and categorical data was exerted as frequencies and percentages (%). The t test or Mann–Whitney U test was employed to compare continuous data, and the χ test or Fisher exact test was placed to compare categorical data. For all statistical analysis, a 2-side P < .05 was defined statistically significant.

Results

Patient baseline features

A total of 130 eligible patients after successful endoscopic hemostasis were enrolled in this study. Of those, 65 patient cases received routine management and IVEO (Group A), and the other 65 patient cases underwent routine treatment only (Group B). The clinical baseline features of 130 patients in both groups are presented in Table 1. All features were balanced between 2 groups in statistics (P > .05, table 1).

Table 1

Comparison of baseline demographics and clinical characteristics.

Characteristics	Group A (n = 65)	Group B (n = 65)	P value
Mean age (yr)	54.4 (12.3)	53.9 (11.7)	.81
Gender
Male	41 (63.1)	45 (69.2)	.46
Female	24 (36.9)	20 (30.8)	–
Race (Asian China)	65 (66.2)	65 (75.4)	–
Body mass index (kg/m2)	22.9 (3.0)	23.1 (3.2)	.71
Current alcohol consumption	23 (35.4)	20 (30.8)	.58
Current smoking	43 (66.2)	49 (75.4)	.25
Helicobacter pylori status
Positive	39 (60.0)	42 (64.6)	.59
Negative	19 (29.2)	18 (27.7)	.85
Unclear	7 (10.8)	5 (7.7)	.55
Previous ulcer disease	20 (30.8)	24 (36.9)	.46
History of peptic ulcer
Duodenal ulcer	15 (23.1)	19 (29.2)	.43
Gastric ulcer	17 (26.2)	13 (20.0)	.41
Both ulcer	3 (4.6)	4 (6.2)	.70
Bleeding ulcer location
Stomach	14 (21.5)	10 (15.4)	.37
Duodenum	51 (78.5)	55 (84.6)	–

Primary outcome in Group A and Group B

Results of recurrent bleeding rate are listed in Table 2. Patients in the Group A achieved better improvement of overall recurrent bleeding rate within 72-hour (P < .05, table 2), 7-day (P < .05, table 2) and 30-day (P < .05, table 2), than that of patients in Group B. However, there were not significant differences in results of recurrent bleeding rate at different time points when patients were grouped based on the type of age and sex (P > .05, table 2).

Table 2

Comparison of recurrent bleeding rate between 2 groups.

Outcomes	Groups	72-hour	7-day	30-day
Overall	Group A (n = 65)	2 (3.1)∗	3 (4.6)∗	3 (4.6)∗
	Group B (n = 65)	9 (13.8)	11 (16.9)	12 (18.5)
Age (yr)
≤65	Group A (n = 65)	1 (1.5)	2 (3.1)	2 (3.1)
	Group B (n = 65)	5 (7.7)	6 (9.2)	8 (12.3)
>65	Group A (n = 65)	1 (1.5)	1 (1.5)	1 (1.5)
	Group B (n = 65)	4 (6.2)	5 (7.7)	4 (6.2)
Gender
Male	Group A (n = 65)	2 (3.1)	2 (3.1)	2 (3.1)
	Group B (n = 65)	7 (10.8)	8 (12.3)	8 (12.3)
Female	Group A (n = 65)	0 (0)	1 (1.5)	1 (1.5)
	Group B (n = 65)	2 (3.1)	3 (4.6)	4 (6.2)

Secondary outcomes in Group A and Group B

There were not significant differences in secondary outcomes of all-cause mortality (Group A, 3.1% vs Group B, 7.7%; P = .26; Table 3), bleeding-related mortality (Group A, 1.5% vs Group B, 3.1%; P = .57; table 3), blood transfused (Group A, 1.57 (2.21)vs Group B, 1.96 (2.38); P = .33; table 3), and hospital stay (day) (Group A, 4.6 (5.0) vs Group B, 4.9 (5.3); P = .74; table 3) between 2 groups.

Table 3

Comparison of secondary outcomes within 30 days between 2 groups.

Outcomes	Group A (n = 65)	Group B (n = 65)	P value
All-cause mortality	2 (3.1)	5 (7.7)	.26
Bleeding-related mortality	1 (1.5)	2 (3.1)	.57
Blood transfused (unit)	1.57 (2.21)	1.96 (2.38)	.33
Hospital stay (d)	4.6 (5.0)	4.9 (5.3)	.74

AEs in Group A and Group B

There were not significant differences in AEs of serious AEs (Group A, 1.5% vs Group B, 3.1%; P = .57; Table 4), duodenal ulcer hemorrhage (Group A, 3.1% vs Group B, 10.8%; P = .10; table 4), gastric ulcer hemorrhage (Group A, 1.5% vs Group B, 7.7%; P = .13; table 4), vomiting (Group A, 1.5% vs Group B, 4.6%; P = .33; table 4), nausea (Group A, 3.1% vs Group B, 6.2%; P = .41; table 4), abdominal pain (Group A, 3.1% vs Group B, 7.7%; P = .26; table 4), constipation (Group A, 3.1% vs Group B, 9.2%; P = .16; table 4), and dyspepsia (Group A, 4.6% vs Group B, 7.7%; P = .47; table 4) between 2 groups.

Table 4

Comparison of AEs between 2 groups.

AEs	Group A (n = 65)	Group B (n = 65)	P value
Serious AEs	1 (1.5)	2 (3.1)	.57
Duodenal ulcer hemorrhage	2 (3.1)	7 (10.8)	.10
Gastric ulcer hemorrhage	1 (1.5)	5 (7.7)	.13
Vomiting	1 (1.5)	3 (4.6)	.33
Nausea	2 (3.1)	4 (6.2)	.41
Abdominal pain	2 (3.1)	5 (7.7)	.26
Constipation	2 (3.1)	6 (9.2)	.16
Dyspepsia	3 (4.6)	5 (7.7)	.47

Discussion

Previous study investigated the efficacy of IVEO prevents recurrent peptic ulcer bleeding in a multiethnic subject.[ Its findings suggest that high-dose IVEO after successful endoscopic treatment can benefit participants with high-risk peptic ulcer bleeding decreased recurrent bleeding within 72 hours and even lasts upon to 30 days.[ Its results partly are consistent with the present study. In this retrospective cohort study, we compared the preventive effect between Chinese NUGIB patients with IVEO combined routine treatment, and routine therapy alone. Our study reported that there were significant differences in preventing recurrent bleeding rate within 72-hour, 7-day, and 30-day between 2 groups. It indicates that IVEO may benefit in preventing recurrent bleeding rate within 30 days after successful endoscopic hemostasis.

On the other hand, we did not detect significant differences in all-cause mortality, bleeding-related mortality, blood transfused, and hospital stay between 2 groups. It suggests that IVEO may not prevent mortality and hospital stay in patients NUGIB. Moreover, no AEs (serious AEs, duodenal ulcer hemorrhage, gastric ulcer hemorrhage, vomiting, nausea, abdominal pain, constipation, and dyspepsia) differed significantly between 2 groups, which showed that treatments in both groups had similar safety profile.

There were several limitations in this retrospective study. The first limitation was its retrospective nature because of the purely observational features when compared with prospective studies. The second limitation was that its very finite sample size made the statistical results that may be inaccurate sufficiently to reach an undisputed conclusion. The third limitation was that a total of 30 days from baseline to the end of observation was quite short. Thus, longer term of preventive effect and safety of IVEO in the prevention of NUGIB should be explored in further studies. To address such limitation, studies should harvest complete data from multiple hospitals to increase its sample size and follow-up period.

Conclusion

The results of this study found that routine management and IVEO can decrease the recurrent bleeding rate after successful endoscopic hemostasis in patients with NUGIB.

Author contributions

Conceptualization: Xing-cheng Sun, Wei-feng Yuan, Wen-jun Zhang, Shuo-gui Xu.

Data curation: Xing-cheng Sun, Wei-feng Yuan, Wen-jie Ma, Shuo-gui Xu.

Formal analysis: Shuo-gui Xu.

Funding acquisition: Shuo-gui Xu.

Investigation: Shuo-gui Xu.

Methodology: Xing-cheng Sun, Wen-jun Zhang.

Project administration: Shuo-gui Xu.

Resources: Xing-cheng Sun, Wei-feng Yuan, Wen-jie Ma, Wen-jun Zhang.

Software: Wen-jie Ma, Wen-jun Zhang.

Supervision: Shuo-gui Xu.

Validation: Xing-cheng Sun, Wen-jie Ma, Shuo-gui Xu.

Visualization: Xing-cheng Sun, Wei-feng Yuan, Wen-jie Ma, Wen-jun Zhang, Shuo-gui Xu.

Writing – original draft: Xing-cheng Sun, Wei-feng Yuan, Wen-jun Zhang, Shuo-gui Xu.

Writing – review & editing: Xing-cheng Sun, Wei-feng Yuan, Wen-jie Ma, Wen-jun Zhang, Shuo-gui Xu.