Implementation of RICA (ERAS) Guidelines in Grade II Acute Cholecystitis Undergoing Early Laparoscopic Cholecystectomy (COLERICA II)

Introduction and Clinical Framework

Acute cholecystitis constitutes one of the most prevalent acute surgical conditions managed within emergency departments across Europe. Epidemiological indicators highlight a rising incidence, particularly within the population over 65 years of age. While cholelithiasis affects approximately 10% to 15% of the general adult population, up to 40% of these individuals experience stone-related complications, with acute cholecystitis serving as the primary clinical manifestation in a substantial proportion of symptomatic cases.

The Tokyo Guidelines 2018 (TG18) represent the international gold standard for the diagnosis and severity stratification of this condition. Grade II (moderate) acute cholecystitis is characterised by marked local inflammation that complicates direct surgical management. Diagnostic features for Grade II include a marked leukocytosis (white blood cell count greater than 18,000/mm³), a tender palpable mass in the right upper abdominal quadrant, or a duration of clinical symptoms exceeding 72 hours. It also encompasses advanced local inflammatory findings confirmed via diagnostic imaging, such as gangrenous, emphysematous, or pericolecystic abscess formations, hepatic abscesses, or biliary peritonitis.

The seminal multi-centre randomised controlled trial (ACDC study) established the clinical superiority of early laparoscopic cholecystectomy over conservative management followed by delayed elective surgery, showing significant reductions in patient morbidity, hospital stay, and resource utilization. Current consensus guidelines from the World Society of Emergency Surgery (WSES) define early cholecystectomy as an intervention performed within 7 days of hospital admission or up to 10 days from the onset of clinical symptoms. While the technical advantages of early surgery in Grade II cases are recognised-offering a viable laparoscopic window before tissue fibrosis sets in-there is a critical lack of standardized perioperative management frameworks tailored specifically for this urgent, moderately severe cohort, as most general Enhanced Recovery After Surgery (ERAS) data originates from elective colorectal or mild (Grade I) cholecystitis pathways.

Study Objectives and Hypotheses

The primary objective of this study is to evaluate the clinical efficiency and recovery optimization of an institutional RICA protocol implementation for TG18 Grade II acute cholecystitis managed via early laparoscopic cholecystectomy. The core hypothesis is that the systematic and multi-professional standardisation of care will significantly reduce the postoperative length of hospital stay (measured precisely in hours) without increasing overall 90-day postoperative morbidity or unplanned hospital readmissions.

The secondary objectives are:

1. To compare baseline characteristics and clinical outcomes between the intervention group and historical controls to assess protocol impact.
2. To monitor perioperative morbidity by tracking the incidence and severity of surgical complications using the Clavien-Dindo classification up to 90 days postoperatively.
3. To determine the rate and underlying causes of unplanned hospital readmissions within a 90-day postoperative window.

Methodology and Work Plan

This investigation employs a quasi-experimental, single-centre, before-after cohort design conducted at the University Hospital of Igualada (Catalonia, Spain). The study architecture is divided into two sequential chronological periods:

• The Retrospective Phase (Historical Control Group, January 2023 - December 2025): Medical records of consecutive patients matching the inclusion criteria who underwent conventional surgical and perioperative care will be reviewed to establish a robust baseline.
• The Prospective Phase (Intervention Group, March 2026 - February 2029): Consecutive patients will be prospectively enrolled, providing written informed consent, and managed strictly in accordance with the multidisciplinary RICA care matrix.

The project timeline dictates a one-week formal introduction to brief and align the departments of General Surgery, Anaesthesiology, and Emergency and Wards Nursing, alongside the deployment of the REDCap data infrastructure. The inclusion and data capture phase spans 36 months, followed by a 6-month data cleaning, 90-day follow-up completion, and final statistical analysis phase. The final 6 months are dedicated to scientific manuscript preparation following the TREND (Transparent Reporting of Evaluations with Nonrandomized Designs) statement guidelines.

The RICA Perioperative Care Matrix

The active intervention evaluated in this study replaces conventional practitioner-dependent management with a highly structured, time-sequenced multimodal care pathway involving surgeons, anaesthetists, and specialised nursing staff. The protocol is structured as follows:

1. Preoperative Stage: Includes point-of-care ultrasound (POCUS) clinical assessment; systematic evaluation of surgical risk and patient frailty using validated clinical frailty scores; strict glycaemic control aiming to maintain blood glucose below 180 mg/dL; targeted antimicrobial prophylaxis governed by hospital antibiotic stewardship guidelines (PROA); active thermal management using forced-air warming blankets for vulnerable or frail individuals; and targeted patient education detailing early recovery objectives.
2. Intraoperative Stage: Use of the surgical safety checklist; routine advanced monitoring; execution of standard or subtotal laparoscopic cholecystectomy (documenting fenestrated or reconstituted approaches, or conversion to open surgery); rapid sequence anaesthetic induction; controlled hyperoxia ($FiO_2$ 0.6 to 0.8); goal-directed fluid therapy (utilising non-invasive advanced haemodynamic monitoring systems like Clearsight) or weight-adjusted restrictive fluid administration (3-5 mL/kg/h); mandatory core normothermia maintenance; strict restriction of routine nasogastric tubes, urinary catheters, or abdominal drainage placement; and the mandatory application of opioid-sparing multimodal analgesia via local wound infiltration or Transversus Abdominis Plane (TAP) blocks.
3. Immediate Postoperative Stage (Day 0): Continued active warming; oxygen therapy adjusted to blood oxygen saturation; multimodal non-opioid analgesia restricting morphic rescue doses; restrictive fluid maintenance; early mobilization protocol requiring sitting within 2 hours and active ambulation within 8 hours post-surgery; and early oral intake initiation (clear fluids) within 6 to 8 hours of the procedure.
4. Postoperative Day 1: Progression to a liquid diet; active ambulation and targeted respiratory physiotherapy; transition to oral analgesia; discontinuation of intravenous fluid lines upon adequate oral tolerance; and initial evaluation for the removal of any intraoperatively placed drains or catheters.
5. Postoperative Day 2 & Extended Stay: Advancement to a progressive low-fat biliary diet; full independent ambulation; continued oral analgesia and PROA-aligned antibiotic therapy; and daily formal assessment against discharge criteria.
6. Discharge and Follow-up Criteria: Discharge is authorized only when the patient meets all standard criteria: absence of fever, adequate pain control via oral analgesia, complete independent ambulation, active patient acceptance, and a pre-discharge objective laboratory check measuring C-Reactive Protein (CRP) and liver function enzymes. Post-discharge care includes an institutional 24-hour telephone follow-up call, coordinated continuity with primary care medical teams, and a formal clinical follow-up assessment at 3 to 4 weeks.

Advanced Statistical Analysis Strategy

All data management will be executed utilizing the REDCap platform. Statistical computing will be performed using R software (version 4.3 or higher), with a fixed significance threshold of $p < 0.05$. Continuous variables will be evaluated for normality via the Shapiro-Wilk test and expressed as mean and standard deviation (SD) or median and interquartile range (IQR). Categorical variables will be analysed using Chi-squared or Fisher's exact tests.

To evaluate the primary outcome (postoperative length of stay in hours), a multivariable linear regression model will be constructed. The dependent variable will be the log-transformed length of stay to account for non-normal distributions, with group allocation (RICA pathway vs. conventional care) serving as the main independent predictor. The model will be adjusted for key baseline covariates exhibiting unbalance, alongside established clinical confounders including age, ASA physical status, clinical frailty score, comorbidities, and initial biochemical severity indicators.

To account for the inherent selection bias of a non-randomised before-after design and mitigate period-related confounding, an advanced sensitivity analysis using Propensity Score Matching (PSM) will be implemented. Propensity scores will be calculated for each patient via a logistic regression model incorporating baseline demographics and clinical risks. Patients from the historical and prospective cohorts will be matched using a 1:1 nearest-neighbour algorithm, creating a balanced sub-cohort to isolate the true therapeutic effect of the RICA intervention.

Furthermore, a Cox proportional hazards regression model will be deployed to evaluate the time-to-discharge rate, treating the hospital discharge as the event of interest, complemented by Kaplan-Meier survival curves. To prove causal association, an institutional compliance index (0% to 100%) will be calculated for each intervention patient based on the percentage of RICA items fulfilled; a linear regression will test the direct correlation between high protocol adherence and reduced hospital stay. For the safety endpoint (Clavien-Dindo complications $\ge$ II), a formal non-inferiority analysis will be performed, applying a pre-specified safety margin of 5% to confirm that the RICA pathway does not compromise patient safety. Missing data patterns will be checked; if random and under 5%, complete-case analysis will be used, otherwise multiple imputation techniques will be applied.