Bryan Zoll, MS4
The Article: Carsten Gutt, Jens Encke, Jorg Koninger, et al. Acute Cholecystitis: Early Versus Delayed Cholecystectomy, A Multicenter Randomized Trial (ACDC study, NCT00447304). Annals of Surgery. 2013;258(3):385 - 393.
Background: Acute cholecystitis (AC) is an inflammatory process of the gallbladder, diagnosed by a combination of local (murphy sign, RUQ pain), systemic (fever, increased CRP, leukocytosis) and sonographic findings. The treatment of such disease, notably the optimal timing at which a surgeon should perform a cholecystectomy, has been debated. Early laparoscopic cholecystectomies (<72hrs from symptom onset) historically were feared due to concern of inflammation mediated surgical complications. Incipient observational studies demonstrated that early cholecystectomies were associated with increased bile duct injury, thus delayed cholecystectomies (>7day following antibiotic course) were favored. However later systemic reviews and small randomized controlled trials demonstrated no significant difference in surgical complication between early and late cholecystectomies. Because cholecystectomy for AC is one of the most common surgical interventions for a general surgeon, and a lack of consensus for optimal timing existed, this study aimed to define best practice by comparing the outcomes of early versus delayed cholecystectomy for AC.
Methods:
Type: Prospective Randomized Controlled Trial
Clinical Setting: 35 study centers in Germany and Slovenia from the years 2006 – 2010.
Population: Adult patients age 18 years and older with signs and symptoms of AC
Inclusion: AC was defined as having at least 3 of the following [(1) abdominal pain in right upper quadrant (2) Murphy sign (3) leukocytosis (4) rectal temp >38 C], in addition to stones/sludge or sonographic signs of cholecystitis. Surgeons needed to be available within 24 hours of presentation for patients to be included in the trial.
Exclusion: American Society of Anesthesiologists (ASA) physical status IV and V, septic shock, perforation or abscess of gall bladder, non-surgical candidates, life expectancy of <48 hours, pregnancy or breast feeding, contraindications of antibiotic used (moxifloxacin).
Design: Eligible patients were block randomized (block size of 4) to either immediate laparoscopic cholecystectomy (<24 hours; ILC) or to conservative treatment followed by elective cholecystectomy (7-45 days; DLC). Both groups were treated with 400mg moxifloxacin once daily, with antibiotic treatment discontinued with clinical improvement. Test of cure and post-surgery survey was performed at day 75 post inclusion.
Statistics: Per protocol and intention to treat analysis were used with a 2 sided significance level of 0.05 with 95% confidence intervals calculated using Mantel-Haenszel weighting.
Results:
Of 642 screened patients, 618 were randomized into the study design: 304 ILC and 314 DLC. Of this, 292 ILC and 258 DLC patients reached endpoint.
The primary outcome measured was morbidity. 35 (12%) of the ILC and 86 (33.3%) of the DLC per protocol patient population had a procedural morbidity. In the intention to treat category, morbidity rates were 11.6% (ILC) and 31.3% (DLC). Both the per protocol and the intention to treat had p<0.05. Primary morbidity was further stratified into ASA pre-morbidity ratings of ≤ 2 vs > 2. ILC morbidity for ASA ≤ 2 was 9.7% compared to 26.6% of DLC. ILC morbidity for ASA >2 was 20.0% compared to 47.5% DLC. Thus, morbidity was higher for DLC vs ILC in all ASA scores, most notable with ASA of >2.
Secondary outcome includes measures such as conversion rate to open surgery, percent adverse events, percent change of antibiotic regiment, mortality rate, mean total hospital stay (days), total mean hospital costs. In sum, adverse events, mean total hospital stay, and mean total hospital costs were significantly decreased for ILC vs DLC (Table 1).
Takeaway: This, at the time, was the largest randomized trial of comparing immediate versus delayed laparoscopic cholecystectomy for AC. The authors conclude that cholecystectomy within 24 hours of presentation AC is superior to delayed (>7d) in both morbidity, adverse events, mean hospital stay, and overall costs. This paper thus suggests that patients who present with AC should receive cholecystectomy within 24 hours of admission to improve outcomes.