Cholecystitis


Background 

  • Inflammatory dz of gallbladder often d/t gallstones
    • 90% d/t stones in the cystic duct (i.e. calculous cholecystitis)
    • 10% acalculous cholecystitis
      • Infxns (microorganism, protozoan, parasites)
      • Ischemia, motility disorders, collagen dz
      • Direct chemical injury, allergic reaction
      • Xanthogranulomatous cholecystitis: stones play a role, but characterized by xanthogranulomatous (foamy histocytic granulomas) thickening of gallbladder wall
      • Emphysematous cholecystitis: air in gallbladder wall from gas-forming anerobes (i.e. C. perfringens), often in DM; can lead to sepsis, gangrene
      • Gallbladder torsion: can be acquired (i.e. sudden change in body position, defecation, blow to abdomen) or inherited (i.e. floating gallbladder: splanchnoptosis, scoliosis)
    • Even though bile cultures usually positive for bacteria (50-75% of cases), bacterial proliferation may be d/t cholecystitis and not the precipitating factor
  • Cholecystitis usually presents commonly w/ upper abdominal pain and fever, but cannot r/o even if asymptomatic
  • Prognosis is good in uncomplicated cholecystitis if Tx
    • Low mortality rate
    • Delays in Dx or Tx can lead to complications and incr morbidity/mortality rates
    • If complications develop (i.e. gangrene, ulceration/perforation), prognosis worsens
      • May require surgical intervention
  • Initial mgmt of acute cholecystitis includes bowel rest, IV hydration, and Abx
    • Outpatient therapy if uncomplicated
    • If surgery is required: laparoscopic cholecystectomy is standard

Pathophysiology

  • Mechanism
    • Acute acalculous cholecystitis most likely d/t endotoxin or bile stasis in gallbladder
      • A study shows lack of cholecystokinin (CCK) stimulation of gallbladder to empty leads to bile stasis
      • Another study shows endotoxin inhibition of gallbladder response to CCK leads to bile stasis
      • Endotoxin-induced necrosis, hemorrhage, fibrosis, and wall mucosal loss
    • Acute calculous cholecystitis d/t obstruction of neck or cystic duct by gallstone
      • Leads to incr pressure in gallbladder causing distention; blood and lymph circulation disrupted
      • Results in mucosal ishemia, necrosis
    • Progression to acute cholecystitis determined by duration and degree of obstruction
      • If complete obstruction and long duration
      • If partial obstruction and short duration, leads to biliary colic
    • Stages of Cholecystitis
      • Stage 1 (edematous): 2-4 days; gallbladder tissue intact w/ edema in subserosal layer, interstitial fluid w/ dilated capillaries and lymphatics
      • Stage 2 (necrotizing): 3-5 days; edematous w/ areas of hemorrhage and necrosis d/t elevated internal pressures compromising blood flow
      • Stage 3 (suppurative): 7-10 days; active inflamm process, WBCs at necrotic and suppurative areas in wall; fibrous wall thickening, intramural abscesses
      • Stage 4 (chronic): after repeated episodes of cholecystitis; mucosal atrophy, wall fibrosis, PMN/lymphocyte/plasma cell infiltration; acute on chronic cholecystitis (chronic irritation by stones)
    • Complications of Cholecystitis
      • Perforation of gallbladder: ischemia/necrosis of wall
      • Biliary peritonitis: bile leakage (i.e. through perforation, incomplete suture) into peritoneum
      • Pericholecystic abscess: wall perforations covered up by surrounding tissue forming abscesses
      • Biliary fistula: duodenal-gallbladder fistula formation, usually d/t erosion of wall into duodenum by large stone; stone can travel to ileocecal valve and cause SBO (gallstone ileus)
         
  • Etiology/Risk Factors
    • Gallstones (90-95%)
    • Acalculous cholecystitis associated with
      • Biliary stasis: including debilitation, major surgery, severe trauma, sepsis, long-term total parenteral nutrition (TPN), and prolonged fasting
      • Cardiac events, sickle cell dz, DM
      • Infections (i.e. salmonella, cytomegalovirus, cryptosporidiosis, microsporidiosis w/ AIDS)
    • Risk Factors
      • Female > males
      • Incr w/ age (most in 55-62 yo)
      • Obesity
      • Whites > Blacks
         
  • Epidemiology
    • Incidence/Prevalence
      • No large epidemiological study to date, but estimated 10% US pop has gallstones
        • Up to 12% develop acute cholecystitis (most frequent complication of gallstones) after 5-7 yrs
        • Up to 6% develop severe acute cholecystitis
      • Prevalence incr w/ age; 2-3 times more in females; US Whites > US Blacks
    • Morbidity/Mortality
      • Uncomplicated cholecystitis has good prognosis, low mortality
      • Most have complete remission in 1-5 days; up to 1/3 may require surgical intervention
      • Perforation may occur in 15% of cases; mortality for calculous cholecystitis is about 1-4%
      • Acalculous cholecystitis can have up to 50% mortality rate

Diagnostics

  • History/Symptoms
    • Upper abdominal pain (most common RUQ) that can radiate to right shoulder/scapula area
      • Initially colicky pain, then constant, severe pain > 6 hrs duration
    • Nausea/vomiting, fever
    • Acalculous cholecystitis may present similiarly, but often present w/ fever and sepsis alone
    • Elderly (esp. elderly w/ DM) may present w/o pain or fever
      • Localized tenderness may not be present or be the only sign
      • May progress to complicated cholecystitis rapidly and w/o warning
         
  • Physical Exam/Signs
    • General, Vitals: fever, guarded, positive Murphy sign, jaundice (15%)
      • Murphy's sign had highest specificity (79-96%) but low sensitivity (20-87.5%)
      • Absence of physical findings does not r/o cholecystitis
      • Elderly and DM may present w/ vague signs, localized tenderness may or may not be present
    • Abd/GI/GU
      • RUQ tenderness (most common); may have diffuse epigastric tenderness w/o RUQ localization
      • Rebound tenderness
      • Palpable gallbladder may be present (chronic cholecystitis may not have palpable gallbladder)
         
  • Labs/Tests
    • Studies shows laboratory data results not reliable in Dx
    • CBC + Diff, electrolytes
      • Leukocytosis, left shift
    • Elevated CRP
    • LFTs
      • Elevated AST/ALT levels
      • Elevated Alk Phos (25% of cases), bilirubin
    • Pancreatic enzymes
      • Elevated amylase, lipase
    • U/A to r/o renal etiology (i.e. kidney stones, renal infxns)
       
  • Imaging
    • Liberal use of biliary scintigraphy or U/S is encouraged to avoid underdiagnosis of acute cholecystitis
    • ERCP useful if high risk for gallstones if common bile duct obstruction
      • Preferred over endoscopic U/S and intraoperative cholangiography if high risk for common bile duct stones undergoing laparoscopic cholecystectomy
    • American College of Radiology (ACR) Imaging Recommendations for Acute Cholecystitis
      • U/S preferred initial imaging modality (scintigraphy is preferred alternative if problematic)
      • Hepatobiliary Scintigraphy (HBS) up to 95% accurate in Dx
        • The presence of Murphy's sign was both sensitive (97.2%) and highly predictive (93.3%) of a positive HBS
      • Dx should be confirmed or excluded w/ sonography and/or scintigraphy
      • CT +/- contrast is secondary (can identify extrabiliary disorders/complications, such as gangrene, perforation)
      • MRI +/- contrast as alternative secondary
      • Contrast agents NOT recommended in dialysis unless benefit outweighs risk
      • Pregnancy recommended least radiation modality (i.e. U/S or MRI)
         
  • Other Tests/Criteria
    • Pregnancy test in all fertile females
    • TG13 Diagnostic Criteria for Acute Cholecystitis
      1. Local signs of inflamm, etc
        1. Positive Murphy's sign
        2. RUQ mass/pain/tenderness
      2. System signs of inflamm, etc
        1. Fever
        2. Elevated CRP
        3. Elevated WBC count
      3. Imaging findings characteristic of acute cholecystitis
        • Thickening gallbladder wall (≥ 5 mm)
        • Pericholecystic fluid/abscess or tenderness of gallbladder ("ultrasonographic Murphy's sign")
        • Gallbladder stones, gallbladder swelling/enlargement, debri echo/gas imaging (gas collection in gallbladder)
        • CT scan shows: gallbladder distention, pericholecystic fat stranding, subserosal edema, mucosal enhancement
    • Suspected Dx: One item in A + one item in B
    • Definitive Dx: One item in A + one item in B + C
    • TG13 Severity Grades for Acute Cholecystitis
      • Grade I (Mild): does not meet criteria of Grade II or III acute cholecystitis
        • Acute cholecystitis in healthy patient
        • No organ dysfunction
        • Mild inflamm changes in gallbladder
        • Cholecystectomy safe/low-risk operative procedure
      • Grade II (Moderate): associated with
        • Elevated WBC (> 18,000/mm3)
        • Palpable, tender mass RUQ
        • > 72 hrs duration of complaints
        • Marked local inflamm (gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary peritonitis, emphysematous cholecystitis)
      • Grade III (Severe): organ dysfunction
        • Cardiovascular: hypotension requiring Tx (dopamine ≥ 5 mcg/kg/min, or any dose of norepi)
        • Neurological: decr LOC
        • Respiratory: PaO2/FiO2 ratio < 300
        • Renal: oliguria, creatinine > 2.0 mg/dL
        • Hepatic: PT-INR > 1.5
        • Hematologic: platelet count < 100,000/mm3
           
  • Differential Diagnosis
    • Cholangitis
    • Biliary colic, Biliary dz
    • Choledocholithiasis, cholelithiasis
    • Gastric/duodenal ulcers, gastritis
    • Hepatitis, pancreatitis
    • Gallbladder cancer/tumors
    • Fitz-hugh-Curtis syndrome
    • RLL pneumonia
    • Angina pectoris, MI
    • Acute pyelonephritis, UTI
    • Appendicitis
    • Mesenteric ischemia

Treatment

  1. Initial/Prep
    • ABCs, electrolytes, IV fluids, monitor respiratory and hemodynamics
      • Fasting may be required for surgical intervention
      • IV fluids and electrolyte replacement will be required after fasting
    • Severity repeatedly assessed using severity assessment criteria
      • At diagnosis, within 24 hr after diagnosis, and again between 24-48 hrs
    • Analgesic administration
      • NSAIDs recommended (i.e. diclofenac)
    • If comorbidities (i.e. shock, LOC, acute renal injurdy, etc), manage w/ appropriate organ support therapies
    • Management algorithms (based on severity assessments)
      • Grade I: initiate Abx and supportive care; observe conservative mgmt or early/elective laparoscopic cholecystectomy
      • Grade II: initiate Abx and supportive care; if failure urgent gallbladder drainage, then cholecystectomy; if success, then elective cholecystectomy
      • Grade III: initiate Abx and general organ support; urgent gallbladder drainage; cholecystectomy
         
  2. Medical/Pharmaceutical
    • Local antimicrobial susceptibility patterns (antibiogram) should be considered for use
    • Ampicillin/sulbactam has little activity left against E. coli and is removed from the North American guidelines
    • Fluoroquinolone use is recommended if susceptibility of cultured isolates is known or for ß-lactam allergies
      • Many extended-spectrum ß-lactamase producing (ESBL+) Gram-neg isolates are fluoroquinolone-resistant
    • Anti-anaerobic therapy (including metronidazole, tinidazole, or clindamycin) warranted if a biliary-enteric anastomosis is present
      • Carbapenems, piperacillin/tazobactam, ampicillin/sulbactam (not in North American guidelines), cefmetazole, cefoxitin, flomoxef, and cefoperazone/sulbactam have sufficient anti-anerobic activity for this situation
    • Vancomycin recommended for Enterococcus spp. for grade III community-acquired acute cholecystitis
    • Linezolid or daptomycin recommended if
      • Vancomycin-resistant Enterococcus (VRE)
      • Previous treatment included vancomycin
      • Organism common in community
    • Grade I (Mild)
      • Ampicillin/sulbactam (not in North American Guidelines): 3 g IV every 6 hrs + aminoglycoside for 2-3 days or
      • Cefazolin, or cefotiam, or cefuroxime, or ceftriaxone, or cefmetazole, or cefotixin, or Flomoxef, or cefoperazone/sulbactam, or cefotaxime +/- metronidazole or
      • Ertapenem: 1 g IV every day or
      • Levofloxacin, pazufloxacin, moxifloxacin +/- metronidazole or
      • Ciprofloxacin: 400 mg IV every 12 hrs +/- metronidazole
    • Grade II (Moderate)
      • Piperacillin/tazobactam: 3.375 g IV every 6 hrs for 7-10 days or
      • Ticarcillin/clavulanate: 3.1 g IV every 6 hrs 7-10 days or
      • Ceftriaxone, or cefotaxime, or cefepime, or cefozopran, or cefoperazone/sulbactam, or ceftazidime ? metronidazole or
      • Ertapenem: 1 g IV every day or
      • Levofloxacin, pazufloxacin, moxifloxacin +/- metronidazole or
      • Ciprofloxacin: 400 mg IV every 12 hrs +/- metronidazole
    • Grade III (Severe)
      • Piperacillin/tazobactam: 3.375 g IV every 6 hrs for 7-10 days or
      • Ticarcillin/clavulanate: 3.1 g IV every 6 hrs 7-10 days or
      • Cefepime, or ceftazidime, or cefozopran ? metronidazole or
      • Imipenem/cilastatin (0.5 g IV every 6 hrs), or Meropenem (1 g q8 hr IV), or doripenem, or ertapenem or
      • Aztreonam ± metronidazole
    • If PCN allergy: imipenem or aztreonam +/- clindamycin
       
  3. Surgical/Procedural
    • Recommended drainage techniques
      • Percutaneous transhepatic gallbladder drainage (PTGBD) for grade II (moderate) cholecystitis if no response to conservative Tx and for grade III
    • Grade I: Early laparoscopic cholecystectomy is the first-line treatment. In patients with surgical risk, observation (follow-up without cholecystectomy) after improvement with initial medical treatment could be indicated
    • Grade II: Elective cholecystectomy after the improvement of the acute inflammatory process is the first-line treatment. If a patient does not respond to initial medical treatment, urgent or early gallbladder drainage is required. Early laparoscopic cholecystectomy could be indicated if advanced laparoscopic techniques are available. Grade II (moderate) acute cholecystitis with serious local complications is an indication for urgent cholecystectomy and drainage
    • Grade III: Appropriate organ support such as ventilatory/circulatory management (noninvasive/invasive positive pressure ventilation and use of vasopressors, etc.) in addition to initial medical treatment is necessary. Urgent or early gallbladder drainage should be performed. Elective cholecystectomy may be performed after the improvement of acute illness has been achieved by gallbladder drainage
       
  4. Prevention
    • General healthy lifestyle may reduce risk
    • Cholecystectomy for prevention of recurrency

Disposition

  1. Patients who have surgery to remove the gallbladder usually do very well
  2. Outpatient Tx for most cases (uncomplicated cholecystitis)
  3. Admit if comorbidities or severe dz requiring surgery
    • NPO, prep for surgery
    • If uncomplicated prep for surgery; liquid or low-fat diet until surgery (physician discretion)
 

Admission Orders: Bacterial Cholangitis

1. Admit to:

2. Diagnosis: Bacterial cholangitis

3. Condition:

4. Vital Signs: q4h. Call physician if BP systolic >160, <90; diastolic. >90, <60; P >120, <50; R>25, <10; T >38.5°C.

5. Activity: Bed rest

6. Nursing: Inputs and outputs

7. Diet: NPO

8. IV Fluids: 0.5-1 L LR over 1h, then D5 ½ NS with 20 mEq KCL/L at 125 cc/h. NG tube at low constant suction. Foley to closed drainage.

9. Special Medications:

-Ticarcillin or piperacillin 3 gm IV q4-6h (single agent) OR

-Imipenem/cilastatin (Primaxin) 1.0 gm IV q6h (single agent) OR

-Ampicillin/sulbactam (Unasyn) 1.5-3.0 gm IV q6h (single agent).

 

10. Symptomatic Medications:

-Hydroxyzine (Vistaril) 25-50 mg IV/IM q4-6h prn MS, nausea.

-Omeprazole (Prilosec) 20 mg PO bid OR

-Famotidine (Pepcid) 20 mg IV/PO q12h.

-Heparin 5000 U SQ q12h OR

-Enoxaparin (Lovenox) 30 mg SQ q12h.
 

11. Extras: CXR, ECG, RUQ ultrasound, HIDA scan, acute abdomen series. GI consult, surgical consult.

12. Labs: CBC, CMP, GGT, amylase, lipase, blood C&S x 2. UA, INR/PTT