Impact of Perioperative Synbiotics on Infectious Complications After Pancreatoduodenectomy - A Randomised Controlled Trial

Aim

To study the role of perioperative synbiotics in decreasing infectious complications after pancreatoduodenectomy (PD)

Objectives:

Primary objective:

To assess the 30-day post-PD infective complications.

Secondary objective:

a)     30-day postoperative non-infectious morbidity

b)     Postoperative length of ICU and hospital stay

Detailed methodology:

Study setting

All the patients undergoing PD and meeting inclusion criteria during the study period will be recruited from Department of Surgical Gastroenterology, AIIMS, Jodhpur.

Duration of study

From 15th May 2024 to 30th November 2025

Sample size

Sommacal H M et al 2015 have reported postoperative infectious complications as 69% in conventional group as compared to 26% in intervention group. To detect a 50% decrease in postoperative infectious complications from the conventional group to the interventional group, we estimate a sample size of 36 patients per group with an alpha error of 5%, power of 80% and 10% contingency dropouts. Thus a total of 72 patients would be enrolled.

Study design

It is a single-center open-label randomized controlled study

Inclusion Criteria:

a)     Patients who undergo PD for any indication

b)    Aged 18-80 years

Exclusion Criteria:

a)     Patients who refused consent

b)    Patients who received therapeutic antibiotics within 1 week before the operation

 Written informed consent for participation will be obtained from each subject before enrolling them for the study. The study will be sent to Institutional Ethical Committee for approval prior to commencement of the study.

Randomization :

Patients will be stratified based on whether they are biliary-stented or non-stented. These will be randomly allocated to the Synbiotic or Conventional Care groups using the Sequentially Numbered Opaque Sealed Envelope (SNOSE) technique. The allocation will be blinded and random. There will be no blinding of study participants or study investigators (open-label)

Preoperative evaluation:

Patients planned for PD will undergo detailed history and clinical examination. Routine laboratory investigations including complete blood counts, liver and renal function tests, serum electrolytes, viral markers and coagulation profile will be done. Side viewing endoscopy with biopsy, contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (MRI) will be done as clinical indicated. Tumor markers (CA 19-9 and CEA) will be performed in all patients suspicious of malignancy.  Baseline serum CRP and Procalcitonin will be done in one day prior to surgery. Patients witll undergo a preoperative anesthetic check-up to assess fitness for PD. All the details will be recorded in a pre-designed proforma. Patients allotted to Synbiotics group will receive one capsule of synbiotics with six probiotic bacteria and one prebiotic, 2 days prior to and 8 days after surgery, as per the following composition:

Sl No

Item

Dosage

| Probiotic

  |1

Lactobacillus sps(acidophilus, rhamnosus, paracasei)

4 billion CFU

|2

Bacillus sps (clausii, mesentericus, lactic acid bacillu)

2 billion CFU

|3

Bifidobacterium lactis

60million CFU

|4

Saccharomyces boulardii

30 million CFU

|5

Streptococcus faecalis

60 million CFU

|6

Clostridium butyricum

4 million CFU

| Prebiotic

  |1

Fructo-oligosaccharides

100 mg

 Surgical procedure:

PD will be performed as per standardized protocol in the Department of Surgical Gastroenterology, AIIMS Jodhpur.

Intraoperative Bile culture :

Before transection of bile duct, bile will be aspirated and sent for culture.  If the patient has CBD stent in situ, upper tip of the stent will be sent for culture.

Post-operative follow-up:

Follow up will be done as per  standardized perioperative protocol. Serum CRP and Procalcitonin will be measured on post-operative day (POD)-1, POD-3 and POD-5. Amylase levels in serum and drain fluid and drain cultures will be sent on POD-3. Postoperative abdominal CECT will be performed when clinically indicated.

After discharge, patients will be followed up till 30 post-operative days and their complications, both infectious and non-infectious, would be recorded.

Statistical analysis

Quantitative data will be expressed as median ± interquartile range, and qualitative data as numbers (percentages). Chi-square and Fisher’s exact test will be used to compare categorical variables. Continuous data will be analyzed with the Mann-Whitney U test. The statistical calculations will be done using the Statistical Package for Social Sciences software (SPSS) version 23.0 (IBM Technologies, Chicago, IL).

Ethical consideration

All study subjects will be included after receiving informed written consent. The patient is not being exposed to extra investigations for inclusion in this study. However, all patients enrolled in the study will receive standard care management and participation in the study will not lead to a change in their usual diagnostic workup, follow-up, or management. All personal data collected during the study will be kept strictly confidential.

The study protocol has been reviewed and approved by the Institute Ethics Committee.