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Acute Cholecystitis and The Timing of Surgery: When is it time to heal with steel?. Vincent C. Schooler, MD Resident Grand Rounds June 6, 2003. Clinical Cases. Case 1 80 yo female 3 days of N/V/RUQ pain PMH: Cholelithiasis, DM, CHF, HTN

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acute cholecystitis and the timing of surgery when is it time to heal with steel

Acute Cholecystitis and The Timing of Surgery:When is it time to heal with steel?

Vincent C. Schooler, MD

Resident Grand Rounds

June 6, 2003

clinical cases
Clinical Cases

Case 1

  • 80 yo female
  • 3 days of N/V/RUQ pain
  • PMH: Cholelithiasis, DM, CHF, HTN
  • WBC 17 (6% bands); Tbili 9, ALP 197, AST 699, ALT 650, Amylase 103, Lipase 19
  • Abd CT  Cholelithiasis with pericholecystic fluid and gallbladder distention
  • HIDA Scan  Cystic duct obstruction
clinical cases3
Clinical Cases

Case 2

  • 48 yo male
  • progressive RUQ pain for 2 weeks
  • PMH: DM, HTN, Obesity
  • WBC 6.8, Tbili 0.8, ALP 88, AST 34, ALT 66
  • Abd U/S: Cholelithiasis in neck of gallbladder, negative Murphy’s sign, No CBD dilatation
clinical questions
Clinical Questions
  • What is the optimal time for surgery in these patients?
  • What is the evidence that supports a laparoscopic approach to patients with acute cholecystitis?
  • What evidence-based clinical factors exist to predict a successful laparoscopic surgical outcome?
  • About 3 million adults in the U.S. have gallstones
  • Elderly, diabetics, obese patients, debilitated patients  increased incidence of gallstones
  • 90% of acute cholecystitis cases due to gallstones
  • Aging is the most significant factor  higher incidence of acute cholecystitis1
  • Acute Cholecystitis is the initial presentation of symptomatic gallstones in 15% - 20% of patients3
acute cholecystitis
Acute Cholecystitis
  • RUQ Pain
  • Fever
  • Leukocytosis
  • Severe persistent pain
  • +/- Jaundice
  • Positive Murphy’s Sign
acute cholecystitis 3
Acute Cholecystitis3
  • Persistent cystic duct obstruction
  • Pain lasts > 4 hours
  • Usually fatty food ingestion  1 hr before pain
  •  Biliary Colic

3= Cleveland Clinic Journal of Med

acute cholecystitis9
Acute Cholecystitis
  • Distention and inflammation of the gallbladder
  • Obstruction of cystic duct  Chemical irritants in the bile
    • Lysolecithin
    • Prostaglandins
acute cholecystitis 2
Acute Cholecystitis2
  • Thickened gallbladder wall or edema
  • Pericholecystic Fluid
  • Sonographic Murphy’s Sign
acute cholecystitis13
Acute Cholecystitis
  • Early stages  Edema and hyperemia
  • Later stages  Adhesions, fibrosis, and necrosis
  • Triangle of Calot visible in early stages

Courtesy of Netter

management of acute cholecystitis
Management of Acute Cholecystitis
  • Supportive care with IVFs, bowel rest, & Abx
  • Almost half of patients have positive bile cultures
  • E. Coli is most common organism
  • Antibiotic choice: Ampicillin + Aminoglycoside

or 3rd generation cephalosporin

management cont
Management cont.
  • No evidence exists showing a definite benefit with use of antibiotics
  • NSAIDs may improve course of acute cholecystitis6
  • SURGERY is the only definitive treatment
management cont16
Management cont.
  • 1st open cholecystectomy: 1886 by Justus Ohage
  • 1st half of 20th Century: Supportive care  delayed open cholecystectomy
  • In 1970’s – mid-1980’s: Open cholecystectomy early in the treatment course
  • “Golden 72 hours” Rule
Studies in early 1980’s  early surgery was better than delayed surgery (using standard open approach)14
  • Laparoscopic surgery developed in late 1980’s
  • Complications from LC dependent on laparoscopic skill of surgeon (major bleeding, wound infection, bile leak, and biliary injury)
  • Was the benefit of early surgery by the open approach true laparoscopically??
timing of surgery
Timing of Surgery
  • Early surgery = Within 72 hours of admission or onset of symptoms
  • Delayed surgery = Supportive care only followed by discharge and readmission in 6-12 weeks for surgery
timing of surgery19
Timing of Surgery
  • Based on patient’s overall risk of surgery
  • American Society of Anesthesiologists (ASA) Scale7 is a guide for decisions on surgery
laparoscopic vs open cholecystectomy
Laparoscopic vs. Open Cholecystectomy

Kiviluoto et al.8

  • 63 pts. randomized to LC vs. OC; > 60 y.o. = 59% vs. 48%
  • 1º endpt = hosp. mortality and morbidity, length of hosp. stay
  • 16% of LC group needed conversion to open
  • No deaths in either group; Hosp. stay average of 2 days shorter in LC group (p=0.0063) 8Lancet 1998.
timing of surgery21
Timing of Surgery

Chandler et al.10

Objective: Compare the safety and efficacy of early vs. delayed laparoscopic cholecystectomy for treatment of acute cholecystitis

Study Design:

  • RCT of 43 pts.
  • Early = LC within 72 hours of admission
  • Delayed = LC after symptom resolution or after 5 days of treatment
  • IVFs, Piperacillin, bowel rest
  • Delayed group also given indomethacin

10Amer Surg 2000

chandler et al
Chandler et al.
  • Inclusion: RUQ pain, WBC ≥ 10K, temp >38ºC, U/S evidence
  • Exclusion: Hx. of PUD, GB perforation, unclear diagnosis


  • No statistically significant decrease in the complication rate in the delayed group

Limitations: Small study group, average age < 40 years old

eldar et al 11
Eldar et al.11

Objective: Determine the optimal timing of laparoscopic cholecystectomy for acute cholecystitis and to evaluate preop. and operative factors associated with conversion from LC to OC

Study Design:

  • 137 patients treated for acute cholecystitis
  • Prospective, non-randomized trial
  • 7 patients excluded due to choledocholithiasis
  • LC done on all patients as soon as diagnosis established
  • Cephazolin given preop to all patients

11World J Surg 1997

eldar et al
Eldar et al.


  • 28% conversion rate overall (37/130 total patients)
  • Mean age 50 in LC group vs. 60 in converted group
  • Patients with lap chole >96 hours after symptom onset higher conversion rate (47% vs. 23%, p=0.022)
  • Complication rate: 8.5% in LC vs. 27% in converted group
eldar et al26
Eldar et al.


  • 3/5 independent factors associated with conversion from LC can be determined preoperatively (WBC, age, hx of biliary disease)
  • 2/4 independent factors associated with complications from LC can be determined preoperatively (WBC, Serum bili)

Limitations: Validation of these factors needed using RCT, small study

timing of surgery27
Timing of Surgery

Lai et al.12

Objective: Define the optimum management between early and delayed laparoscopic cholecystectomy

Study Design:

  • Average age in each group of 56 years old
  • Early group = LC within 24 hrs of randomization
  • Delayed group = LC in 6-8 wks

12Brit J Surg 1998

timing of surgery28
Timing of Surgery

Lai et al.


  • No major bile duct injuries in either group
  • 21% (early) vs. 24% (delayed) conversion rate
  • No statistically significant difference in conversion rate, postop. pain or complications
  • 16% of delayed group had a recurrence and failed conservative Rx


  • Early LC better than delayed LC due to lower conversion rate and potentially lower risk of complications

Limitations: Selection bias (exclusion of patients with sxs > 1 week)

timing of surgery29
Timing of Surgery

Lo et al.13

Objective:Compare early with delayed laparoscopic chole. (LC) for acute cholecystitis

Study design:

  • Early = LC within 72 hrs of admission
  • Delayed = LC 8-12 weeks after resolution of acute attack

13Annals Surg 1998

lo et al
Lo et al.

Inclusion: RUQ tenderness, T > 37.5ºC, WBC > 10K, U/S evidence

  • 44% of patients in trial had symptoms for  3 days
  • Median age of 60 years old


  • 16% of patients in delayed group failed conservative Rx. urgent LC
timing of surgery31
Timing of Surgery

Lo et al.


  • Lower hosp. stay and recuperation period in early vs. delayed group (5 days vs. 7 days)
  • Key factor that is controllable in the timing of surgery involves delay from admission to surgery
  • Delayed group  more fibrotic adhesions on gallbladder  increased conversion rate and morbidity
  • Optimal timing of LC is within 72 hours of admission

Limitations: Low number of obese patients, unclear how many diabetics in trial

timing of surgery32
Timing of Surgery

Koo et al.4

Objective: Review the results of laparoscopic cholecystectomy (LC) in patients with acute cholecystitis with attention to cost and clinical outcome

Study Design:

  • Retrospective review of 60 patients who had LC for acute cholecystitis

Exclusion: Patients with histopathologic evidence of acute cholecystitis due to pancreatitis or carcinomatosis and patients without definite signs and symptoms of acute cholecystitis

4Arch Surg 1996

timing of surgery33
Timing of Surgery

Koo et al.

  • 3 groups based on timing of surgery
    • Group 1: LC within 72 hours of onset of symptoms
    • Group 2: LC between 4th and 7th day of symptom onset
    • Group 3: LC after 7 days of symptoms


timing of surgery34
Timing of Surgery

Koo et al.


  • Group 1 (LC within 72 hrs of sxs) had lower conversion rate, shorter & less costly operations, and shorter convalescent rates
  • More severe inflammation in gallbladders from groups 2 and 3
  • NS relation: WBC, LFTs, or U/S findings and conversion rate
  • Patients presenting within 72 hrs. from symptom onset  LC
  • Patients presenting after 72 hrs. from sxs. onset  consider elective LC in 6-8 weeks

Limitations: Selection bias, No description of patient demographics of each group

clinical predictive factors
Clinical Predictive Factors

Schafer et al.15

Objective: Define preop. criteria to predict both the surgical strategy for managing acute cholecystitis and the severity of inflammation

Study Design:

  • 236 patients with acute cholecystitis had LC or OC within 48 hours of admission
  • Non-randomized decision for LC vs. OC
  • Resected gallbladders classified into 3 subgroups
    • Type I (Mucosal inflammation); Type II (Phlegmonous inflammation); Type III (Gangrenous or necrotizing inflammation)

Inclusion: RUQ tenderness, fever, leukocytosis, elevated CRP levels, U/S findings

15Amer J Surg 2001

schafer et al40
Schafer et al.


  • CRP levels, duration of symptoms, WBC count determined to be preoperative parameters that predict the severity of inflammation
  • 5 independent parameters that determine the type of surgical approach (CRP levels, WBC count, ASA class, duration of symptoms, and age)
  • Increased CRP levels associated with advanced inflammation of gallbladder
schafer et al41
Schafer et al.
  • As severity of inflammation increased  complication rate increased
  • CRP levels > 100 mg/L related to local tissue necrosis
  • Defined a set of preoperative conditions that may help determine the safest method of surgery


  • Elevation of CRP levels may be also due to bacterial infection (Trial did not evaluate for it)
  • Selection bias
  • Validation of markers needed with RCT
  • Timing of Surgery not evaluated
clinical predictive factors42
Clinical Predictive Factors

Rattner et al.16

Objective: Determine which preoperative data correlates with successful completion of a laparoscopic cholecystectomy in patients with acute cholecystitis

Study Design:

  • 20 of 281 pts. with acute cholecystitis had LC between 1990-92 at Mass General Hospital

Inclusion: Fever, leukocytosis, RUQ tenderness, intraoperative findings of severe acute inflammation, pathologic evidence of AC

Exclusion: Intraoperative findings of AC but no clinical signs, lab signs, or pathologic evidence of AC

16Annals Surg 1993

rattner et al
Rattner et al.


  • Degree of leukocystosis, ALP elevation, and APACHE II scores were significantly associated with failure of laparoscopic surgery
  • Interval from admission to surgery: 0.6 days (successful group) vs. 5 days (failure group)
  • Failure of LC related to gangrenous changes in gallbladder
rattner et al44
Rattner et al.


  • Surgery within 48 hrs of admission  successful LC
  • Optimal timing of surgery is as soon as possible after diagnosis of acute cholecystitis

Limitations: Retrospective, small study, recall bias (authors of study reviewed their own surgical cases), laparoscopic expertise unknown

clinical cases follow up
Clinical Cases Follow-up

Case 1:

  • 48 hrs after admission: LC  converted to open chole due to adhesions in RUQ and necrosis of her gallbladder
  • Diagnosis: Acute obstructive cholecystitis
  • Uneventful recovery

Case 2:

  • 4 days after admission: LC  converted to open chole due to necrosis of the gallbladder and cystic duct junction
  • Diagnosis: Acute Necrotizing Cholecystitis
  • Uneventful recovery
  • LC compared with OC has decreased pain and disability without an increase in morbidity or mortality
  • LC is more cost-effective
  • Outcome of LC influenced by expertise of surgeon
  • ASA scale useful but difficult to classify all patients
  • Percutaneous cholecystostomy useful alternative in ASA IV, V patients BUT 50% still require surgery15
  • Conversion from laparoscopic to open cholecystectomy should not be viewed as a complication
  • Conversion must occur if anatomy is obscured or excessive bleeding occurs18
  • Most significant clinical factor for successful LC is the duration of symptoms
  • Increased chance of gangrene of the gallbladder after 72 hrs
  • Elderly, diabetics, obese patients, and debilitated patients can safely undergo laparoscopic cholecystectomy for acute cholecystitis
  • Should be performed within 72 hrs of admission
  • If > 72 hours since admission, then evidence supports attempted lap chole with a low threshold for conversion to an open procedure
  • More data needed to determine role of CRP levels in preoperative management of patients with acute cholecystitis