Fast Track Pathway to Accelerated Cholecystectomy
Fast Track Pathway to Accelerated Cholecystectomy
More than 10% of Canadians have gallstones, and approximately 10% of these individuals will
 develop gallbladder inflammation related to gallstones, which is referred to as acute
 cholecystitis (AC). Patients with AC who do not have their gallbladder surgically removed
 have a 30% risk of serious complications that can lead to death. Surgery is the only
 definitive treatment for AC, however, there is controversy regarding the ideal timing of
 surgery. The two main approaches are early surgery (typically within 7 days of diagnosis) or
 delayed surgery (7 days to 6 weeks after diagnosis). Although preliminary evidence suggests
 that early surgery is associated with shorter hospital length of stay, lower risk for
 complications, and lower costs, practice varies widely regarding the timing of surgery. The
 limitations of the existing studies include small sample sizes, varied definitions of early
 versus delayed surgery, and an imbalance of risk between study groups. The proposed pilot
 study aims to inform the design of a large clinical trial that will compare the outcomes of
 patients with AC who receive accelerated surgery (i.e., as soon as possible with a goal of
 surgery within 6 hours of diagnosis) with those who receive standard care.
The prevalence of gallstones is 10% and approximately 10% of patients develop acute
 cholecystitis (AC). AC prevalence increases with age and complications are as high as 30% in
 patients who do not undergo surgery, the only definitive treatment. There is controversy
 regarding ideal surgical timing. Previously, delayed surgery was thought to decrease bile
 duct injuries resulting from active inflammation. However, the state of persistent
 inflammation, hypercoagulability, and stress can cause medical complications such as
 myocardial injury. Chronic inflammation can lead to fibrosis, adhesions and higher chance of
 bile duct injuries during delayed surgery. There is also concern for recurrent AC episodes,
 recurrent pain, biliary pancreatitis, cholangitis or sepsis.

 Recent studies suggest that early surgery may be associated with better outcomes, but
 practice remains variable, ranging anywhere from early surgery (<7 days) to delayed surgery
 (>7 days). Among >24,000 Ontarians with AC admitted to 106 hospitals, timing of
 cholecystectomy varied widely across sites. Only 58% of patients underwent surgery within 7
 days. High volume hospitals were more likely to perform early surgery.17

 Among 14,200 Ontarians with AC, a propensity score analysis demonstrated that early surgery
 was associated with less bile duct injury (relative risk (RR)=0.53, 95% confidence interval
 (CI) 0.31-0.90) and shorter length of hospital stay (LOS) (mean 1.9 days, 95% CI 1.7-2.1).
 Early surgery was less costly and more effective than delayed cholecystectomy.

 Trials of surgical timing in patients with AC are limited. The largest randomized controlled
 trial (RCT) compared early and delayed surgery for AC only included 618 patients.9
 Cholecystectomy was performed a median of 1 day after randomization in the early group
 compared to a median of 25 days in the delayed group. Duration of surgery and conversion rate
 to open surgery were similar in both groups. Early surgery was associated with less morbidity
 (11.8% vs. 34.4%, p<0.001), shorter LOS (5.4 vs. 10.0 days, p<0.001), and lower cost (€2919
 vs. €4262, p<0.001).

 Multiple meta-analyses have suggested that early surgery for AC is associated with fewer
 wound infections (RR 0.57; 95% CI 0.35-0.93) and have suggested a trend to fewer
 complications (RR 0.66; 95% CI 0.42-1.03). Limitations of these meta-analyses include studies
 with small sample sizes, few events, wide confidence intervals, and variation in the
 definition of early surgery. Finally, there is a lack of strong evidence to make definitive
 conclusions regarding impact of early surgery in AC, which has led to substantial variation
 in clinical practice.

 AC initiates inflammatory, hypercoagulable, and stress states that can cause medical
 complications. Early surgical treatment will reduce the time patients are exposed to these
 harmful states and therefore may reduce the risk of complications. Furthermore, rapid surgery
 results in a shorter period of AC, which may impact hospital costs. The goal is to undertake
 a large multicentre RCT of the impact of accelerated surgery (goal within 6 hours of
 diagnosis) vs. usual timing of surgery in patients with AC on a composite outcome of major
 clinical and surgical complications at 90 days. "Standard of care", as described, is highly
 variable and depends on the surgeon and hospital practice patterns.

 The main objective of this pilot study is to assess the feasibility of a large trial. The
 team hypothesizes that accelerated surgery for AC will improve clinical and surgical
 outcomes. A large RCT on this topic is needed for the following reasons: 1) time to surgery
 is a modifiable factor; 2) available data are encouraging, but not definitive; 3) there is
 variation in clinical practice across Ontario and internationally 4) the definition of early
 surgery has varied substantially across studies; 5) available data may be substantially
 underestimating the effect of timing of surgery because no trial has evaluated surgery within
 6 hours of diagnosis; 6) high-quality evidence will modify clinical practice; and 7)
 implementation of accelerated surgery could save millions of healthcare dollars annually.
1. Age ≥45 years; or age ≥18 years and <45 years with at least one of the following
 co-morbidities: diabetes or chronic respiratory, cardiovascular, or renal disease;

 2. Diagnosis of acute cholecystitis defined by the presence of at least 2 of the
 following:

 1. Abdominal pain in upper right quadrant,

 2. Murphy's sign,

 3. Leukocytosis >10 × 103/μl, or

 4. Oral temperature <36.5°C or >38°C;

 3. Cholelithiasis (stones/sludge);

 4. Ultrasound signs of cholecystitis;

 5. Acute cholecystitis that requires surgery and is diagnosed during working hours;

 6. Expected to require at least an overnight hospital admission after surgery; and

 7. Provide written informed consent to participate in FAST.

 Exclusion Criteria

 1. Patients requiring emergent surgery or emergent interventions for another reason;

 2. Patients whose therapeutic anticoagulation is not reversible;

 3. Patients with a history of heparin-induced thrombocytopenia and current use of
 warfarin with an INR ≥1.5;

 4. Pregnant patients;

 5. Previous participation in the trial.