Clinical trial NCT05518643: Compliance With ERAS Protocol in Pancreatic Surgery, Stress Response and Outcomes
Official title: Enhanced Recovery Program, Patient Reported Outcomes, Surgery-specific Outcomes and Stress Response After Pancreatic Surgery: A Prospective Observational Cohort Study by the Thessalic Pancreas Study Group (ThePANas).
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: ERAS
Pancreas Cancer
Pancreas; Fistula
Delayed Gastric Emptying
Surgery-Complications
Pancreatic Hemorrhage
PROMs
Keywords: ERAS
Pancreas Cancer
PROMs
Stress response to surgery
Surgery-Complications
PLR
NLR
Quality of Life
Lead sponsor: University of Thessaly
Sponsor class: OTHER
Collaborators: name: IASO Thessalias
name: Larissa University Hospital
First posted: 2022-08-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive community patients presented for pancreatic surgery

Brief summary: The purpose of this study is to evaluate the impact of compliance with enhanced recovery after surgery (ERAS) program on patient reported outcomes (PROs), surgery-specific outcomes and stress response after pancreatic surgery.

This prospective observational study will include all consecutive patients undergoing pancreatic surgery over a period of three years (2022 - 2025) at two sites, namely University General Hospital of Larissa and IASO Thessalias, in Greece. Patients will be prospectively enrolled after written informed consent. Data will be collected on patient characteristics, surgical and anaesthetic techniques, complications, and length of stay. Quality of life questionnaires will be administered to patients preoperatively, on the fith postoperative day, first follow-up after discharge, one month and six months after the operation. The stress response will be assessed by measuring the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio (NLR and PLR) preoperatively, and on the first five postoperative days. Data will be collected on pancreatic surgery-specific complications such as delayed gastric emptying (DGE), post-pancreatectomy haemorrhage (PPH) and postoperative pancreatic fistula (POPF) formation. Anonymised data will be uploaded by the principal investigator on a protected excel spreadsheet for analysis.

Detailed description: In this study the ERAS program is applied to patients undergoing pancreatic surgery.This is a prospective observational cohort study.The study will take place in two hospitals, the University General Hospital of Larissa (academic center), and IASO Thessalias (largest private general hospital in Thessaly). The study period is three years between May 2022 and April 2025. All patients undergoing pancreatic surgery during this period will be invited to participate in the study. Recruitment will take place at the first appointment with the surgeon when the patient is listed for surgery. The patient will be provided with detailed information about the program which also includes an information leaflet. A written consent form will be signed by patients willing to participate in the study.

Enrolled patients will follow the ERAS pathway for pancreatic surgery during the preoperative, intraoperative, and postoperative period. The ERAS protocol is based on ERAS society recommendations for enhanced recovery after pancreatoduodenectomy.

The ERAS protocol consists of the following items:

First appointment preoperative:

* Patient education about the program
* Prehabilitation with advice on physical exercise and nutritional support
* Advice to stop smoking and alcohol consumption
* Plan for optimisation of comorbidities
* Completion of quality of life questionnaire

Day before surgery:

* Discussion about the program to address any patient concerns and anxieties
* Light meal and carbohydrate drink before bedtime
* Anti-clotting injection 12 hours before surgery

Day of surgery:

* Carbohydrate drink and painkillers 3 hours before surgery
* Clear fluids allowed up to 3 hours before surgery
* Antibiotics within 1 hour before surgical incision

Intraoperative

* Epidural catheter is sited before general anaesthesia
* Multimodal and opioid-sparing analgesia
* Nausea and vomiting prophylaxis
* Goal directed fluid therapy
* Active warming to avoid hypothermia
* Monitoring of blood glucose to maintain normoglycaemia
* Bile culture
* Repeat antibiotics if surgery lasts more than 4 hours

Postoperative:

* Removal of nasogastric tube by postoperative day 1
* Removal of drains by postoperative day 3
* Multimodal analgesia, epidural catheter for 3 days, minimisation of opioids
* Early and scheduled mobilisation and respiratory physiotherapy protocol
* Diet protocol with nutritional drinks and gradual progression from light to solid diet by postoperative day 5
* Removal of urinary catheter when patients able to mobilise on their own, by postoperative day 5
* Cessation of intravenous fluids when patients able to drink 1.5 liters of water, by postoperative day 5
* Regular gastrokinetic medication and gum chewing
* Glycaemic control protocol
* Cessation of antibiotics if bile culture negative and no other indication to continue

The study group will use a checklist with ERAS criteria to follow for each patient and data will be collected on adherence rates to these criteria.

Data will be collected on patient demographics such as sex, age, Body Mass Index (BMI), American Society of Anaesthesiologists (ASA) physical status, and co-morbidities. Data will also be collected on surgical approach and technique, and tumour stage (pTNM). Data will be collected on complications including cardiovascular and respiratory complications, infectious complications (surgical site infection, chest infection, urinary tract infection, intra-abdominal abscess, sepsis), anaesthetic complications (severe pain, delirium, cognitive decline), functional complications (functional decline, new mobility aid use, pressure ulcer, discharge to nursing or rehabilitation facility), renal failure, ileus, return to theatre, readmission, and death. Data will be collected on length of stay and pancreatic surgery-specific complications such as DGE, PPH and POPF formation. International consensus guidelines will be used for definition and grading of these complications.

Quality of life will be assessed by Patient Reported Outcome Measures (PROMS). The stress response will be assessed by measuring NLR and PLR. After anonymization, all data will be prospectively uploaded by local investigators on a protected database and incorporated into a spreadsheet for data analysis.

The data will be analyzed using PROMs, NLR and PLR ratios, postoperative complications, length of hospital stay and cancer recurrence rates as the main outcome variables.The influence of the following factors will be assessed: age, BMI, sex, surgical technique, pTNM stage, preoperative comorbidity, ASA classification, previous SARS-CoV-2 infection, and compliance to the ERAS protocol (\<50%, 50-70%, 70-90%, \>90%). Adherence will be calculated as the number of interventions fulfilled/20 (total number of preoperative and perioperative interventions).

The statistical model will be multivariate regression analysis. Sample size guidelines for observational studies with regression analysis are based on simulation studies and suggest that the minimum number of events per variable (EPV) should be 10. According to these guidelines the minimum sample size is calculated at 90. To account for 25% loss to follow-up the investigators aim for a total enrollment goal of 120 participants. IBM® SPSS 26 software will be used for statistical analysis. Continuous variables will be compared with One-Way ANOVA or Student's t test for parametric data and with a non-parametric test (Mann-Whitney U test or Kruskal-Wallis test), as indicated. Categorical data will be analysed by using the chi squared or Fisher's exact test where indicated. Quantitative values will be expressed as mean ± standard deviation (SD), median and range, categorical data with percentage frequencies. The odds ratio (OR) will be presented followed by 95% confidence interval (95% CI). Differences in survival and complications between different degrees of compliance will be assessed by the application of log rank test. P \< 0.05 will be considered statistically significant.

Eligibility criteria: Inclusion Criteria:

* all pancreatic surgery patients
* above the age of 18
* fluent greek speakers
* without communication barriers

Exclusion Criteria:

* younger than 18 years-old
* unable or unwilling to participate
* other surgical procedures
* communication barriers
* lost to follow-up

Primary outcomes:
measure: Change in patient-reported outcomes as measured by the Health Questionnaire EORTC QLQ-C30
timeFrame: 1 week to 1 day before the operation, postoperative day 5, first follow-up 1 week post discharge, 1 month, and 6 months after the operation
measure: Change on the stress response to surgery measured by the Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio (NLR and PLR).
timeFrame: 1 week to 1 day before the operation, and postoperative days 1-5
measure: Rate of Delayed Gastric Emptying (DGE)
timeFrame: within 6 weeks from operation
measure: Rate of Post Pancreatic Fistula (POPF) formation
timeFrame: within 6 weeks from operation
measure: Rate of Postoperative Pancreatic Haemorrhage (PPH)
timeFrame: within 6 weeks from operation
Secondary outcomes:
measure: Length of hospital stay (LOS)
timeFrame: within 6 weeks from operation
measure: Overall morbidity rate
timeFrame: Within 3 months from operation
measure: Cancer recurrence rate
timeFrame: within 1 year from operation
Other outcomes:
Locations:
city: Larissa
country: Greece
facility: University of Thessaly
Study officials:
affiliation: University of Thessaly, IASO Thessalias
name: Despoina Liotiri, Consultant
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Thessaly
name: Dimitrios Zacharoulis, Professor
role: STUDY_CHAIR
affiliation: University of Thessaly
name: Eleni Arnaoutoglou, Professor
role: STUDY_DIRECTOR
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