Efficacy of Somatostatin Combined with Omeprazole for Non-Variceal Gastrointestinal Bleeding

Summary

This protocol focuses on a reproducible EMR-based data extraction and analysis workflow that can be applied by other institutions to evaluate pharmacological treatment strategies in non-variceal upper gastrointestinal bleeding (NVUGIB) using retrospective clinical datasets.

Abstract

This study presents a structured, reproducible retrospective workflow for evaluating combination pharmacological therapy in patients with non-variceal upper gastrointestinal bleeding (NVUGIB) using electronic medical record (EMR) data. The goal of this protocol is to provide a standardized framework for extracting, processing, and analyzing retrospective clinical data to assess treatment outcomes. The workflow includes database querying, application of inclusion and exclusion criteria, group allocation based on treatment records, and systematic extraction of predefined clinical and laboratory outcomes. Data are analyzed using a stepwise statistical approach to generate representative outcomes. Representative results demonstrate that combination therapy with somatostatin and omeprazole is associated with improved haemostatic outcomes, reduced rebleeding rates, and enhanced clinical recovery compared with omeprazole alone, without an increase in adverse events. These findings are hypothesis-generating and should be interpreted as association-based observations.

This protocol emphasizes reproducibility and can be applied across institutions to evaluate pharmacological interventions using retrospective clinical datasets. The method provides a practical framework for clinicians and researchers to assess treatment effectiveness in real-world settings and may be adapted to other therapeutic areas requiring retrospective outcome evaluation.

Introduction

Upper gastrointestinal hemorrhage is a common medical emergency and can be life-threatening when the bleeding is massive¹. Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common cause of upper gastrointestinal bleeding, with a high morbidity and mortality rate, including gastric and duodenal ulcers, rapid-onset gastric mucosal injury, and a small number of upper gastrointestinal tract malignant tumors such as gastric carcinoma caused by necrotic hemorrhage, whose risk factors include old age, Helicobacter pylori infection, and the use of non-steroidal anti-inflammatory drugs, etc^2,3,4. NVUGIB is primarily caused by peptic ulcers and mucosal injury, while malignant causes are less common and were not included in this study. Therefore, the management of NVUGIB remains a significant clinical challenge in contemporary practice. In addition to pharmacological therapy, endoscopic intervention and interventional radiology are commonly used approaches; However, standardized workflows for evaluating pharmacological interventions using retrospective clinical datasets remain limited⁵. The goal of this protocol is to provide a reproducible workflow for evaluating pharmacological treatment outcomes in NVUGIB using retrospective EMR data.

In recent years, somatostatin and its analogues have been increasingly used in NVUGIB. Somatostatin is a synthetic cyclic peptide that exerts multiple biological effects through different receptor subtypes. It inhibits the secretion of gastric acid, pepsin, and gastrin, stimulates the secretion of gastric mucus, promotes platelet coagulation and clot constriction, and antagonizes the dilatation of visceral blood vessels by glucagon, thus reducing gastrointestinal blood flow, but has no effect on coronary arteries or systemic haemodynamics^6,7. Therefore, somatostatin not only protect the gastric mucosa and promote mucosal proliferation, but also make the bleeding blood vessels less susceptible to erosion by gastric acid, and the scabs and clots are less likely to fall off, so that the bleeding can be rapidly controlled, thus achieving the purpose of hemostasis^8,9.

Proton pump inhibitors (PPIs) represent the most advanced pharmacological option for peptic ulcer management. They achieve efficient and rapid inhibition of gastric acid secretion and eradication of Helicobacter pylori to promote rapid ulcer healing and have superior efficacy in upper gastrointestinal bleeding. PPIs, including omeprazole, are currently the standard of care for non-variceal upper gastrointestinal bleeding according to international guidelines^10,11. Compared to prospective randomized trials, retrospective EMR-based workflows offer faster implementation and lower resource requirements, although they may be subject to confounding. The present study therefore tests whether adding somatostatin to this standard PPI therapy provides additional clinical benefit. Omeprazole, as a proton pump inhibitor, can irreversibly bind with H⁺-K⁺ -ATPase in the mural cells, blocking the final step of gastric acid secretion, thus strongly and persistently inhibiting the secretion of gastric acid, accelerating platelet aggregation, accelerating coagulation, and inactivating pepsin, stabilizing the formed blood crusts, causing the bleeding to stop rapidly and preventing rebleeding^12,13. The combination of somatostatin and omeprazole was selected due to their complementary mechanisms of action, and a retrospective design allows evaluation of real-world clinical effectiveness using existing patient data. A retrospective EMR-based approach enables efficient evaluation of real-world treatment outcomes without the need for prospective intervention.

NVUGIB carries high morbidity and mortality, prompting a search for better treatments; numerous reports indicate that somatostatin (or its analogues) combined with a PPI is significantly more effective than monotherapy^14,15. However, limited studies have systematically evaluated this combination using a structured retrospective workflow, highlighting the need for standardized assessment of its clinical effectiveness. Previous studies have primarily focused on clinical efficacy, but few have provided a structured methodological framework for retrospective evaluation. This study presents a structured workflow for evaluating combination therapy outcomes using retrospective clinical data. This method is particularly suitable for institutions with access to structured EMR systems and sufficient retrospective patient data.

Protocol

Ensure that the study protocol complies with the ethical principles outlined in the Declaration of Helsinki. Obtain formal approval for this retrospective study from the Institutional Review Board (IRB) of The First People's Hospital of Jiashan (Approval No.: 2025-081). Obtain written informed consent from all participating patients prior to enrollment. Document the signed consent forms in the patients' medical records and retain them in the study files.

Note: As this was a retrospective study using de-identified EMR data, the Institutional Review Board granted a waiver of informed consent; no prospective consent was obtained.

1. Database query and initial screening (Figure 1)

1. Access the hospital's electronic medical record (EMR) system.
2. Execute a query to identify all patients admitted with a primary or secondary diagnosis of upper gastrointestinal bleeding (UGIB) between January 1, 2022, and December 31, 2024.
3. Export the initial patient list, including medical record numbers, admission dates, and discharge diagnoses.

2. Application of inclusion and exclusion criteria

1. Review the full EMR of each patient from the initial list sequentially.
2. Define sample size
   1. Define the sample size based on retrospective data availability.
   2. Include all consecutive patients who meet the predefined inclusion and exclusion criteria during the study period (January 2022 – December 2024).
   3. Include 55 patients per group (110 total).
   4. Perform post-hoc power analysis based on the primary outcome (24 h hemostasis rate: 87.3% vs. 70.9%).
   5. Use n = 55 per group and α = 0.05 to determine that the achieved power is approximately 72%.
   6. Interpret secondary outcomes with smaller absolute differences or event rates (e.g., ICU admission rate: 5.5% vs. 16.4%) as underpowered, exploratory, and hypothesis-generating.
3. Include a patient if they meet all of the following criteria:
   1. Include patients aged between 18 and 80 years.
   2. Underwent diagnostic upper gastrointestinal endoscopy during admission.
   3. Include patients with an endoscopic diagnosis of non-variceal bleeding (peptic ulcer, acute gastric mucosal lesion, Mallory-Weiss syndrome)¹⁶.
   4. Include patients presenting with active bleeding or high-risk stigmata (Forrest classification Ib, IIa, or IIb)¹⁷.
   5. Include patients with complete clinical data records (endoscopy reports, medication charts, vital signs, laboratory results)¹⁸.
   6. Include patients with a hospital stay of at least 72 h from admission to allow complete assessment of 72 h rebleeding and laboratory outcomes.
4. Exclude a patient if they meet any of the following criteria:
   1. Exclude patients with bleeding from oesophageal or gastric varices.
   2. Exclude patients with a bleeding source identified as a malignant tumor.
   3. Exclude patients with severe concomitant cardiac, hepatic, or renal insufficiency, or a known coagulation disorder¹⁹.
   4. Exclude patients who are pregnant or lactating.
   5. Exclude patients with a documented allergy to omeprazole or somatostatin²⁰.
   6. Exclude patients who underwent therapeutic endoscopy (e.g., clipping, coagulation) or surgery for hemostasis within 48 h prior to the index admission²¹.
   7. Exclude patients who were on long-term non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulants at the time of admission²².
   8. Document the reason for exclusion for each ineligible patient in a screening log.
      NOTE: The screening process can be paused after initial patient identification and resumed after data verification.
      CAUTION: Ensure that all patient data are handled in compliance with institutional privacy and data protection regulations.

3. Baseline characteristics abstractionm

1. For each included patient, meticulously review the physician's orders and nursing medication administration records from the first 72 h of admission.
2. Assign patients to treatment groups based on recorded therapy
   1. Review each patient’s medical records to identify administered treatments.
   2. Assign the patient to the Combination Group (add-on therapy) if records show concurrent administration of intravenous omeprazole and continuous intravenous somatostatin infusion.
   3. Assign the patient to the Control Group (standard care alone) if records show administration of intravenous omeprazole alone.
3. As treatment allocation was not randomized, this observational grouping may introduce confounding by indication; future studies should incorporate multivariable adjustment.
4. Assign the patient to the Control Group if their records show administration of intravenous omeprazole alone.
5. Verify group allocation by a second independent reviewer. Resolve any discrepancies through discussion and consensus, referring to the pharmacy dispensing records if necessary.

4. Baseline characteristics abstraction

1. Create a standardized data collection form.
2. For each patient, extract the following baseline data from the admission notes and initial laboratory reports:
   1. Age (years) and sex.
   2. Primary cause of bleeding (peptic ulcer, acute mucosal lesion).
   3. Forrest classification from the initial endoscopy report (Ib, IIa, IIb).
   4. Admission haemoglobin level (g·L^-1).
   5. Comorbidities: presence of hypertension and/or diabetes mellitus (yes/no).

5. Treatment regimen documentation

1. Record the specific pharmacological treatment for each patient.
   NOTE: For omeprazole (all patients in both groups): All patients received a strictly identical standardized regimen: an initial intravenous bolus of 80 mg, followed by continuous intravenous infusion at 8 mg/h for 72 h. No patient in either group received a higher or lower dose of omeprazole. This regimen was uniform across both the combination and control groups, ensuring that any outcome difference cannot be attributed to differential PPI dosing.
2. For somatostatin (Combination Group only): Document the loading dose (250 µg slow intravenous bolus), followed by the maintenance infusion rate (250 µg·h^-1) for 72 h.
   NOTE: Dose–response relationships were not evaluated due to uniform dosing across all patients
3. Record the start time and total duration of each drug administration for each patient.
4. Perform the index endoscopy within 24 h of admission by attending gastroenterologists (≥ 5 years of experience) using a standard video gastroscope.
5. Classify bleeding stigmata using the Forrest system. Include only patients with active bleeding or high-risk stigmata (Forrest Ib, IIa, IIb).
6. Repeat endoscopy for suspected rebleeding, defined as active bleeding (Forrest Ia·Ib^-1) or visible vessel (Forrest IIa).
7. Follow-up endoscopy at 12 months to assess the ulcer healing (complete re-epithelialization or Forrest III).
8. Review all reports by a second gastroenterologist blinded to group allocation, with consensus reached by discussion for ambiguous cases.

6. Primary efficacy outcome assessment

NOTE: Define and assess the following hemostasis outcomes based on recorded clinical data:

1. 24 h hemostasis Rate:
   1. Review nursing notes, vital sign charts, and laboratory results for the first 24 h post-treatment initiation.
   2. Define hemostasis criteria as cessation of haematemesis/melena; systolic blood pressure (SBP) ≥ 90 mmHg and heart rate ≤ 100 bpm without vasopressors; haemoglobin decline < 2 g·dL^-1 without transfusion; follow-up endoscopy showing Forrest IIc/III lesions (if performed).
   3. Verify criteria using clinical records. Code the patient as "Yes" for 24 h hemostasis if all criteria are met; otherwise, code as "No".
2. 48 h hemostasis Rate:
   1. Extend the review period to 48 h.
   2. Define sustained hemostasis as maintaining the criteria from step 6.1.2 for the 24–48 h period, without recurrence of bleeding or need for rescue intervention (repeat endoscopy, surgery).
   3. Code accordingly.
3. 72 h Rebleeding Rate:
   1. Review data from 0 to 72 h.
   2. Define rebleeding as any of the following after initial hemostasis: fresh haematemesis/melena with a Hb drop ≥ 2 g·dL^-1; haemodynamic instability (SBP < 90 mmHg) requiring intervention; endoscopic confirmation of active rebleeding.
   3. Code the patient as "Yes" for rebleeding if any criterion is met.

7. Secondary clinical outcome assessment

1. Review data from 0 to 72 h.
2. Length of Hospital Stay: Calculate the total number of days from admission to discharge. Use the documented discharge criteria: stable vital signs for 24 h, no bleeding, and stable haemoglobin.
3. Blood Transfusion Volume: Sum the total units of packed red blood cells transfused during the entire hospitalization. Confirm against transfusion service records.
4. Record ICU admission status based on documented transfer records.

8. Symptom relief time assessment

1. Abdominal Pain Relief (≤ 12 h):
   1. Locate serial pain assessments in the nursing charts, typically using a Visual Analogue Scale (VAS, 0-10)²³.
   2. Define relief as a reduction in VAS score by ≥ 50% from baseline, resulting in a score ≤ 3, sustained for at least 2 h.
   3. Record the time from treatment initiation to meeting this criterion. Code as "Success" if ≤ 12 h; otherwise, "Failure".
2. Cessation of Haematemesis (≤ 6 h):
   1. Review records of gastric aspirate (if nasogastric tube placed) or documented episodes of vomiting.
   2. Define cessation as no fresh blood or coffee-ground material observed in two consecutive assessments 2 h apart.
   3. Record the time to meet this criterion. Code as "Success" if ≤ 6 h.

9. Laboratory parameter measurement

1. Identify the relevant laboratory test results in the EMR.
   ​NOTE: The following tests are performed by the hospital's central laboratory using standard operating procedures.
2. Sample Collection: Confirm that venous blood samples were collected in appropriate tubes: EDTA tubes for haemoglobin (Hb) and white blood cell count (WBC); serum separator tubes for blood urea nitrogen (BUN), C-reactive protein (CRP), and procalcitonin (PCT).
3. Parameter extraction:
   1. Record the admission values for Hb, BUN, CRP, PCT, and WBC.
   2. Record the values for the same parameters at 72 h (± 6 h) after treatment initiation.
   3. Calculate the change (Δ) for each parameter: value at 72 h minus value at admission.

10. Long-term follow-up data collection

1. Review outpatient clinic records for scheduled follow-ups at 1, 3, 6, and 12 months post-discharge.
2. Cumulative rebleeding and ulcer healing outcomes reported in this study are based on the 12-month follow-up time point.
3. Rebleeding Event: Document any episode of suspected rebleeding (haematemesis, melena, significant Hb drop) confirmed by clinic visit or readmission records.
4. All patients in both groups underwent follow-up endoscopy at 12 months post-discharge. Ulcer healing was assessed based on the endoscopy report. Healing was defined as complete re-epithelialization (white scar) or Forrest III lesion. Code as "Healed" or "Not Healed". The denominator for ulcer healing rate is therefore the full group size (n = 55 per group).
5. For patients without clinical records, attempt to obtain data via structured telephone interview, documenting the date and source of information.

11. Safety and adverse event assessment

1. Systematically review all progress notes, nursing flow sheets, and laboratory alerts during the hospitalization.
2. Record the presence or absence of the following pre-specified adverse events: nausea/vomiting, headache, diarrhea, and hyperglycaemia (blood glucose > 10 mmol·L^-1 without prior history).
3. Document any other unexpected clinical events noted in the records.

12. Data preparation and software setup

1. Systematically review all progress notes, nursing flow sheets, and laboratory alerts during the hospitalization.
2. Open Microsoft Excel. Enter all abstracted data from the paper-based collection forms into a master spreadsheet. Save the file as "NVUGIB_study_data.xlsx" in.xlsx format. Use the first row as variable names.
3. Launch IBM SPSS Statistics (version 26.0). Wait for the application to load completely.
4. Import the master spreadsheet into SPSS: Click File > Open > Data. In the dialog box, change the file type to "Excel (.xlsx)".
5. Navigate to and select "NVUGIB_study_data.xlsx".
6. Click Open. In the "Opening Excel Data Source" dialog, check the box "Read variable names from the first row of data".
7. Click OK to create the working data file.
8. Given multiple statistical comparisons, interpret the results with p-values close to 0.05 should be interpreted cautiously, and no formal correction for multiple testing was applied; therefore, findings are considered exploratory.
9. Missing values: Click Analyze > Descriptive Statistics > Frequencies.
10. Select all variables. Check the box "Display frequency tables". Click OK. Review the output. For any variable with "Missing" count > 0, return to the Data View window.
11. Identify the corresponding cell and re-refer to the original source document. Correct the value or enter "999" for missing numeric data (define "999" as "missing" in the Variable View under "Values").
12. Outliers: For continuous variables (e.g., Age, Admission Hb), click Analyze > Descriptive Statistics > Explore.
13. Move all continuous variables into the "Dependent List".
14. Click Plots, check "Boxplots" > "Dependents together".
15. Click Continue, then OK. In the output, identify any circle or star symbols beyond the whiskers in the boxplot. For any value beyond 1.5 × interquartile range (IQR), re-check against the original source document.
16. Inconsistencies: For categorical variables (e.g., Sex: 1 = Male, 2 = Female), click Analyze > Descriptive Statistics > Crosstabs.
17. Run each categorical variable against itself to identify illegal codes. If any value outside the defined range (e.g., "3" for Sex) appears, re-refer to the source document and correct the data entry error.

Results

A total of 110 patients met the inclusion and exclusion criteria for this trial. These results demonstrate the successful implementation of the retrospective workflow for patient selection and group allocation. They were divided into the intervention group and the control group based on the intervention method, with 55 patients in each group. The demographic characteristics and baseline data of the subjects in the two groups were analysed and were not statistically significant (p > 0.05), i.e, the two groups ...

Discussion

NVUGIB is primarily caused by peptic ulcers, mucosal lesions, and non-malignant conditions; tumor-related bleeding was excluded from this study²⁴. Clinical evidence positions proton pump inhibitors as the most efficacious pharmacological option for peptic ulcer management, which can rapidly cure ulcers by efficiently and rapidly inhibiting gastric acid secretion and removing Helicobacter pylori, and also have a better effect on upper gastrointestinal bleeding, which is currently the main therapeut...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Biochemistry Analyzer	Roche	Cobas 8000	Used for blood urea nitrogen (BUN) detection.
Cardiac Monitoring System	Philips	IntelliVue MX550	Used for continuous monitoring of blood pressure and heart rate.
CRP Detection Kit (Immunoturbidimetric Method)	Roche	CRP Latex Kit (Cat. No. 03002889)	Used for C-reactive protein (CRP) detection.
EDTA Anticoagulation Tubes	BD Vacutainer	368861	Used for venous blood collection for Hb testing.
Electrochemiluminescence Analyzer	Roche	Cobas e601 (ECLIA)	Used for procalcitonin (PCT) detection.
Electronic Endoscope	Olympus	GIF-H290	Used for endoscopic diagnosis, rebleeding confirmation, and ulcer healing assessment.
Flow Cytometry System (within DxH 800)	Beckman Coulter	Integrated in DxH 800	Used for WBC counting and classification.
Fully Automated Hematology Analyzer	Beckman Coulter	DxH 800	Used for hemoglobin (Hb) and white blood cell (WBC) detection. WBC differential count is performed using VCS technology (Volume, Conductivity, Scatter) , not flow cytometry.
Glucose Meter	Roche	Accu-Chek Performa	Used for monitoring blood glucose levels.
Nasogastric Tube	Covidien	14Fr	Used for gastric drainage and monitoring of hematemesis.
Normal Saline (0.9% NaCl)	Baxter	2B1324	Used as diluent for intravenous medications.
Omeprazole for Injection	AstraZeneca	Approval No. H20030945	Proton pump inhibitor used in both groups.
Serum Separation Tubes (SST)	BD Vacutainer	367988	Used for venous blood collection for BUN, CRP, and PCT testing.
Somatostatin for Injection	Merck Serono	Taiwan FDA License No. 021333	Used in combination group for visceral blood flow reduction.
SPSS Statistical Software	IBM	Version 26.0	Used for data analysis and statistical testing.
Syringe Infusion Pump	B. Braun	Perfusor Space	Used for continuous administration of somatostatin (250 μg/h).
Visual Analogue Scale (VAS)	Department-printed paper version	Not applicable	Used for abdominal pain assessment (0–10 points).