CHOLECYCTITIS

Background: Cholecystitis is defined as inflammation of the gallbladder that occurs most commonly because of an obstruction of the cystic duct from cholelithiasis. Ninety percent of cases involve stones in the cystic duct (ie, calculous cholecystitis), with the other 10% representing acalculous cholecystitis. Although bile cultures are positive for bacteria in 50-75% of cases, bacterial proliferation may be a result of cholecystitis and not the precipitating factor. Risk factors for cholecystitis mirror those for cholelithiasis and include increasing age, female sex, certain ethnic groups, obesity or rapid weight loss, drugs, and pregnancy.

Acalculous cholecystitis is related to conditions associated with biliary stasis, including debilitation, major surgery, severe trauma, sepsis, long-term total parenteral nutrition (TPN), and prolonged fasting. Other causes of acalculous cholecystitis include cardiac events; sickle cell disease; Salmonella infections; diabetes mellitus; and cytomegalovirus, cryptosporidiosis, or microsporidiosis infections in patients with AIDS.


Pathophysiology: Acute calculous cholecystitis is caused by obstruction of the cystic duct, leading to distention of the gallbladder. As the gallbladder becomes distended, blood flow and lymphatic drainage are compromised, leading to mucosal ischemia and necrosis. A study by Cullen et al (2000) demonstrated the ability of endotoxin to cause necrosis, hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent with an acute ischemic insult. Endotoxin also abolished the contractile response to cholecystokinin (CCK), leading to gallbladder stasis.

Although the exact mechanism of acalculous cholecystitis is unclear, a couple of theories exist. Injury may be the result of retained concentrated bile, an extremely noxious substance. In the presence of prolonged fasting, the gallbladder never receives a CCK stimulus to empty; thus, the concentrated bile remains stagnant in the lumen.


Frequency:


In the US: An estimated 10-20% of Americans have gallstones, and as many as one third of these people develop acute cholecystitis. Cholecystectomy for either recurrent biliary colic or acute cholecystitis is the most common major surgical procedure performed by general surgeons, resulting in approximately 500,000 operations annually.
Internationally: Cholelithiasis, the major risk factor for cholecystitis, has an increased prevalence among people of Scandinavian descent, Pima Indians, and Hispanic populations, whereas cholelithiasis is less common among individuals from sub-Saharan Africa and Asia.
Mortality/Morbidity:

Most patients with acute cholecystitis have a complete remission within 1-4 days. However, 25-30% of patients either require surgery or develop some complication.
Patients with acalculous cholecystitis have a mortality rate ranging from 10-50%, which far exceeds the expected 4% mortality rate observed in patients with calculous cholecystitis. Emphysematous cholecystitis has a mortality rate approaching 15%.
Perforation occurs in 10-15% of cases.
Race:

Pima Indian and Scandinavian people have the highest prevalence of cholelithiasis and, consequently, cholecystitis.
Populations at the lowest risk reside in sub-Saharan Africa and Asia.
In the United States, white people have a higher prevalence than black people.
Sex:

Gallstones are 2-3 times more frequent in females than in males, resulting in a higher incidence of calculous cholecystitis in females.
Elevated progesterone levels during pregnancy may cause biliary stasis, resulting in higher rates of gallbladder disease in pregnant females.
Acalculous cholecystitis is observed more often in elderly men.
Age: The incidence of cholecystitis increases with age. The physiologic explanation for the increasing incidence of gallstone disease in the elderly population is unclear. The increased incidence in elderly men has been linked to changing androgen-to-estrogen ratios.




CLINICAL Section 3 of 11
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History:

The most common presenting symptom of acute cholecystitis is upper abdominal pain, often radiating to the tip of the right scapula.
Most patients with acute cholecystitis describe a history of biliary pain. Some patients may have documented gallstones. Acalculous biliary colic also occurs, most commonly in young–to–middle-aged females. The presentation is almost identical to calculous biliary colic with the exception of reference range laboratory values and no findings of cholelithiasis on ultrasound.
Frequently, the pain begins in the epigastric region and then localizes to the right upper quadrant (RUQ). Although the pain may initially be described as colicky, it becomes constant in virtually all cases.
Signs of peritoneal irritation may be present, and, in some patients, the pain may radiate to the right shoulder or scapula.
Nausea and vomiting are generally present, and patients may report fever.
In elderly patients, pain and fever may be absent, and localized tenderness may be the only presenting sign. Patients with acalculous cholecystitis may present similarly to patients with calculous cholecystitis, but acalculous cholecystitis frequently occurs suddenly in severely ill patients without a prior history of biliary colic. Often, patients with acalculous cholecystitis may present with fever and sepsis alone, without history or physical examination findings consistent with acute cholecystitis.
Cholecystitis is differentiated from biliary colic by the persistence of constant severe pain for more than 6 hours.
Physical:

Physical examination may reveal fever, tachycardia, and tenderness in the RUQ or epigastric region, often with guarding or rebound.
A palpable gallbladder or fullness of the RUQ is present in 30-40% of cases.
Jaundice may be noted in approximately 15% of patients.
The absence of physical findings does not rule out the diagnosis of cholecystitis. Many patients present with diffuse epigastric pain without localization to the RUQ. Patients with chronic cholecystitis frequently do not have a palpable RUQ mass secondary to fibrosis involving the gallbladder.
Elderly patients and patients with diabetes frequently have atypical presentations, including absence of fever and localized tenderness with only vague symptoms.
Murphy sign, which is specific but not sensitive for cholecystitis, is described as tenderness and an inspiratory pause elicited during palpation of the RUQ.
Causes:

Risk factors for calculous cholecystitis mirror those for cholelithiasis and include the following:
Female sex
Certain ethnic groups (see Race)
Obesity or rapid weight loss
Drugs (especially hormonal therapy in women)
Pregnancy
Increasing age
Acalculous cholecystitis is related to conditions associated with biliary stasis, to include the following:
Critical illness
Major surgery or severe trauma/burns
Sepsis
Long-term TPN
Prolonged fasting
Other causes of acalculous cholecystitis include the following:
Cardiac events, including myocardial infarction
Sickle cell disease
Salmonella infections
Diabetes mellitus
Patients with AIDS with cytomegalovirus, cryptosporidiosis, or microsporidiosis
Idiopathic cases exist.
DIFFERENTIALS Section 4 of 11
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Abdominal Aortic Aneurysm
Acute Mesenteric Ischemia
Amebic Hepatic Abscesses
Appendicitis
Biliary Colic
Biliary Disease
Cholangiocarcinoma
Cholangitis
Choledocholithiasis
Cholelithiasis
Gallbladder Cancer
Gallbladder Mucocele
Gallbladder Tumors
Gastric Ulcers
Gastritis, Acute
Gastroesophageal Reflux Disease
Hepatitis, Viral
Myocardial Infarction
Nephrolithiasis
Pancreatitis, Acute
Peptic Ulcer Disease
Pneumonia, Bacterial
Pregnancy and Urolithiasis
Pyelonephritis, Acute
Renal Disease and Pregnancy
Renal Vein Thrombosis




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WORKUP Section 5 of 11
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Lab Studies:


A retrospective study by Singer (1996) attempted to determine a set of clinical and laboratory parameters that could be used to predict the outcome of hepatobiliary scintigraphy (HBS) in all patients with suspected acute cholecystitis.
The results of the study showed that, in 40 patients with pathologically confirmed acute cholecystitis, fever and leukocytosis were absent at the time of presentation in 36 (90%) and 16 (40%) of the patients, respectively.
The study also found that no combination of laboratory or clinical values was useful in identifying patients at high risk for a positive HBS finding.
Although laboratory criteria are not reliable in identifying all patients with cholecystitis, the following findings may be useful in arriving at the diagnosis:
Leukocytosis with a left shift may be observed in cholecystitis.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are used to evaluate the presence of hepatitis and may be elevated in cholecystitis or with common bile duct obstruction.
Bilirubin and alkaline phosphatase assays are used to evaluate evidence of common duct obstruction.
Amylase/lipase assays are used to evaluate the presence of pancreatitis. Amylase may also be elevated mildly in cholecystitis.
An elevated alkaline phosphatase level is observed in 25% of patients with cholecystitis.
Urinalysis is used to rule out pyelonephritis and renal calculi.
All females of childbearing age should have pregnancy testing.
Imaging Studies:


Radiography (without contrast)
Gallstones may be visualized in 10-15% of cases. This finding only indicates cholelithiasis, with or without active cholecystitis.
Subdiaphragmatic free air cannot originate in the biliary tract, and, if present, it indicates another disease process.
Gas limited to the gallbladder wall or lumen represents emphysematous cholecystitis, usually because of gas-forming bacteria such as Escherichia coli and clostridial and anaerobic streptococci species. Emphysematous cholecystitis is associated with an increased mortality rate and occurs most commonly in males with diabetes and with acalculous cholecystitis.
A diffusely calcified gallbladder (ie, porcelainized) most commonly is associated with carcinoma, although one retrospective study by Towfigh (2001) found no association between partial calcification of the gallbladder and carcinoma.
Other findings may include renal calculi, intestinal obstruction, or pneumonia.
Ultrasonography
Ultrasonography provides greater than 95% sensitivity and specificity for the diagnosis of gallstones more than 2 mm in diameter. Ultrasonography is 90-95% sensitive for cholecystitis and is 78-80% specific. Studies indicate that emergency physicians require minimal training in order to use right upper quadrant ultrasonography in their practice.
Ultrasonographic findings that are suggestive of acute cholecystitis include the following: pericholecystic fluid, gallbladder wall thickening greater than 4 mm, and sonographic Murphy sign. The presence of gallstones also helps to confirm the diagnosis.
Ultrasonography is performed best following a fast of at least 8 hours because gallstones are visualized best in a distended bile-filled gallbladder.
Hepatobiliary scintigraphy (hepatoiminodiacetic acid [HIDA]/diisopropyl iminodiacetic acid [DISIDA])
HBS has been found to be up to 95% accurate in diagnosing acute cholecystitis. The reported sensitivities and specificities of biliary scintigraphy are in the range of 90-100% and 85-95%.
In a typical study, the gallbladder, common bile duct, and small bowel fill within 30-45 minutes.
If the gallbladder is not visualized, intravenous morphine administration can improve the accuracy of HBS by increasing resistance to flow through the sphincter of Oddi, resulting in filling of the gallbladder if the cystic duct is patent. The addition of morphine also reduces the number of false-positive scan results observed in patients who are critically ill and immobilized with viscous bile.
Computed tomography scan and MRI
The sensitivity and specificity of CT/MRI scans for predicting acute cholecystitis have been reported to be greater than 95%. Spiral CT scans and MRI (unlike endoscopic retrograde cholangiopancreatography [ERCP]) have the advantage of being noninvasive, but they have no therapeutic potential and are most appropriate in cases where stones are unlikely.
Findings suggestive of cholecystitis include wall thickening (>4 mm), pericholecystic fluid, subserosal edema (in the absence of ascites), intramural gas, and sloughed mucosa.
A CT/MRI scan is also useful for viewing surrounding structures if the diagnosis is uncertain.
Procedures:


Endoscopic retrograde cholangiopancreatography
ERCP may be useful in patients at high risk for common duct gallstones if signs of common bile duct obstruction are present.
A study performed by Sahai et al (1999) found that ERCP was preferred over endoscopic ultrasound and intraoperative cholangiography for patients at high risk for common duct stones undergoing laparoscopic cholecystectomy.
ERCP allows visualization of the anatomy and may be therapeutic by removing stones from the common bile duct.
Disadvantages include the need for a skilled operator, high cost, and complications such as pancreatitis, which occurs in 3-5% of cases.
Histologic Findings: Edema and venous congestion are early acute changes. Acute cholecystitis is usually superimposed on a histologic picture of chronic cholecystitis. Specific findings include fibrosis, flattening of the mucosa, and chronic inflammatory cells. Mucosal herniations known as Rokitansky-Aschoff sinuses are related to increased hydrostatic pressure and are present in 56% of cases. Focal necrosis and an influx of neutrophils may also be present. Advanced cases may show gangrene or perforation.
TREATMENT Section 6 of 11
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Medical Care: For acute cholecystitis, initial treatment includes bowel rest, intravenous hydration, analgesia, and intravenous antibiotics. For mild cases of acute cholecystitis, antibiotic therapy with a single broad-spectrum antibiotic is adequate. Some options include the following:

Current Sanford guide recommendations include ampicillin (4-6 g/d), ampicillin/sulbactam (Unasyn, 3 g IV/IM q6h), or piperacillin/tazobactam (Zosyn, 3.375 g IV q6h). (In severe life-threatening cases, the Sanford Guide also recommends Primaxin or meropenem.)
For severe cases of acute cholecystitis, gentamicin (3-5 mg/kg/d) with clindamycin (1.8-2.7 g/d) or metronidazole with a third-generation cephalosporin provides adequate coverage.
Bacteria that are commonly associated with cholecystitis include E coli and Bacteroides fragilis and Klebsiella, Enterococcus, and Pseudomonas species.
Emesis can be treated with antiemetics and nasogastric suction.
Because of the rapid progression of acute acalculous cholecystitis to gangrene and perforation, early recognition and intervention are required.
Supportive medical care should include restoration of hemodynamic stability and antibiotic coverage for gram-negative enteric flora and anaerobes if biliary tract infection is suspected.

Daily stimulation of gallbladder contraction with intravenous CCK has been shown by some to effectively prevent the formation of gallbladder sludge in patients receiving TPN.
Surgical Care: Laparoscopic cholecystectomy is the standard of care for the surgical treatment of cholecystitis. Surgery is usually performed after symptoms have subsided but during the hospitalization for acute illness. For elective laparoscopic cholecystectomy, the rate of conversion from a laparoscopic procedure to an open surgical procedure is approximately 5%. The conversion rate for emergency cholecystectomy where perforation or gangrene is present may be as high as 30%.

Immediate cholecystectomy or cholecystotomy is usually reserved for complicated cases in which the patient has gangrene or perforation.
Early operation within 72 hours of admission has both medical and socioeconomic benefits and is the preferred approach for patients treated by surgeons with adequate experience in laparoscopic cholecystectomy.
For patients at high surgical risk, placement of a sonographically guided, percutaneous, transhepatic cholecystostomy drainage tube coupled with the administration of antibiotics may provide definitive therapy.
Results of studies suggest that most patients with acute acalculous cholecystitis can be treated with percutaneous drainage alone.
Contraindications for laparoscopic cholecystectomy include the following:
High risk for general anesthesia
Morbid obesity
Signs of gallbladder perforation such as abscess, peritonitis, or fistula
Giant gallstones or suspected malignancy
End-stage liver disease with portal hypertension and severe coagulopathy
Consultations:

Definitive therapy involves cholecystectomy or placement of a drainage device; therefore, consultation with a surgeon is warranted.
Consultation with a gastroenterologist for consideration of ERCP may also be appropriate if concern exists of choledocholithiasis.
Diet: Patients admitted for cholecystitis should receive nothing by mouth (NPO) because of expectant surgery. However, in uncomplicated cholecystitis, a liquid or low-fat diet may be appropriate until the time of surgery.



MEDICATION Section 7 of 11
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The goals of pharmacotherapy are to reduce morbidity and prevent complications.


Drug Category: Antiemetics -- Patients with cholecystitis frequently experience associated nausea and vomiting. Antiemetics can help to make the patient more comfortable and can prevent fluid and electrolyte abnormalities.Drug Name
Promethazine (Phenergan, Prorex, Anergan) -- For symptomatic treatment of nausea in vestibular dysfunction. Antidopaminergic agent effective in treating emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to brainstem reticular system.
Adult Dose 12.5-25 mg PO/IV/IM/PR q4h prn
Pediatric Dose <2 years: Contraindicated
>2 years: 0.25-1 mg/kg PO/IV/IM/PR q4-6h prn
Contraindications Documented hypersensitivity; <2 years (incidences of death due to respiratory depression)
Interactions May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in patients with cardiovascular disease, impaired liver function, seizures, sleep apnea, and asthma
Drug Name
Prochlorperazine (Compazine) -- May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system. In addition to antiemetic effects, it has the advantage of augmenting hypoxic ventilatory response, acting as a respiratory stimulant at high altitude.
Adult Dose 5-10 mg PO/IM tid/qid; not to exceed 40 mg/d
2.5-10 mg IV q3-4h prn; not to exceed 10 mg/dose or 40 mg/d
25 mg PR bid
Pediatric Dose 2.5 mg PO/PR q8h or 5 mg q12h prn; not to exceed 15 mg/d
IV dosing is not recommended for children
0.1-0.15 mg/kg per dose IM; change to PO as soon as possible
Contraindications Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease
Interactions Coadministration with other CNS depressants or anticonvulsants may cause additive effects; coadministration with epinephrine may cause hypotension
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Drug-induced Parkinson syndrome or pseudoparkinsonism occurs frequently; akathisia is the most common extrapyramidal reaction in elderly persons; lowers seizure threshold; caution in patients with history of seizures
Drug Category: Antibiotics -- Treatment of cholecystitis with antibiotics should provide coverage against the most common organisms, including E coli, B fragilis, and Klebsiella, Pseudomonas, and Enterococcus species. Current Sanford guide recommendations for the treatment of cholecystitis include Unasyn, Zosyn, and Timentin for non–life-threatening cases of cholecystitis. In life-threatening cases, Sanford recommends Primaxin or meropenem. Alternatives include gentamicin plus clindamycin or metronidazole with a third-generation cephalosporin.Drug Name
Ampicillin and sulbactam (Unasyn) -- Drug combination of beta-lactamase inhibitor with ampicillin. Covers epidermal and enteric flora and anaerobes. Not ideal for nosocomial pathogens.
Adult Dose 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV/IM q6-8h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin
Pediatric Dose 3 months to 12 years: 100-200 mg ampicillin per kg/d (150-300 mg Unasyn) IV divided q6h
>12 years: Administer as in adults
Contraindications Documented hypersensitivity
Interactions Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction
Drug Name
Piperacillin and tazobactam (Zosyn) -- Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.
Adult Dose 3.375 g IV q6h
Pediatric Dose 75 mg/kg IV q6h
Contraindications Documented hypersensitivity; treating severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis with a PO penicillin during acute stage
Interactions Tetracyclines may decrease effects of piperacillin; high concentrations of piperacillin may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels; high-dose parenteral penicillins may cause increased risk of bleeding
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Perform CBC counts before initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT levels during therapy; caution in hepatic insufficiencies; perform urinalysis and BUN and creatinine determinations during therapy and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions
Drug Name
Gentamicin (Garamycin) -- Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.
Not DOC. Consider if penicillins or other less-toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.
Adult Dose Serious infections and normal renal function: 3 mg/kg/d IV q8h
Loading dose: 1-2.5 mg/kg IV
Maintenance dose: 1-1.5 mg/kg IV q8h
Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV/IM q6-8h
Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion
Pediatric Dose <5 years: 2.5 mg/kg per dose IV/IM q8h
>5 years: 1.5-2.5 mg/kg per dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults
Contraindications Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents; prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment
Drug Name
Metronidazole (Flagyl) -- Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except Clostridium difficile enterocolitis).
Adult Dose Loading dose: 15 mg/kg or 1 g for 70-kg adult IV over 1 h
Maintenance dose: 6 h following loading dose, infuse 7.5 mg/kg or 500 mg for 70-kg adult over 1 h q6-8h; not to exceed 4 g/d
Pediatric Dose Administer as in adults
Contraindications Documented hypersensitivity
Interactions May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy
Drug Name
Clindamycin (Cleocin) -- Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose 150-450 mg/dose PO q6-8h; not to exceed 1.8 g/d
600-1200 mg/d IV/IM divided q6-8h depending on degree of infection
Pediatric Dose 8-20 mg/kg/d PO as hydrochloride or 8-25 mg/kg/d as palmitate divided tid/qid
20-40 mg/kg/d IV/IM divided tid/qid
Contraindications Documented hypersensitivity; regional enteritis; ulcerative colitis; antibiotic-associated colitis; hepatic impairment
Interactions Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of C difficile
Drug Name
Imipenem and cilastatin (Primaxin) -- For treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated because of potential for toxicity.
Base initial dose on severity of infection, and administer in equally divided doses.
Adult Dose 250-500 mg q6h IV; not to exceed 3-4 g/d
Alternatively, 500-750 mg q12h IM or intra-abdominally
Pediatric Dose <12 years: Not established; 15-25 mg/kg/dose IV q6h suggested for >3 mo
Fully susceptible organisms: Not to exceed 2 g/d
Moderately susceptible organisms: Not to exceed 4 g/d
Contraindications Documented hypersensitivity
Interactions Coadministration with cyclosporine may increase CNS adverse effects of both agents; coadministration with ganciclovir may result in generalized seizures
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Adjust dose in renal insufficiency
Drug Name
Levofloxacin (Levaquin) -- For pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Adult Dose 500 mg PO qd for 7-14 d
Pediatric Dose <18 years: Not recommended
>18 years: Administer as in adults
Contraindications Documented hypersensitivity
Interactions Antacids and iron and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Drug Category: Analgesics -- Pain is a prominent feature of cholecystitis. Classic teaching is that morphine is not the agent of choice because of the possibility of increasing tone at the sphincter of Oddi. Meperidine has been shown to provide adequate analgesia without affecting the sphincter of Oddi and, therefore, is the DOC.Drug Name
Meperidine (Demerol) -- DOC. Analgesic with multiple actions similar to those of morphine. May produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine.
Adult Dose 50-150 mg PO/IV/IM/SC q3-4h prn
Pediatric Dose 1-1.8 mg/kg (0.5-0.8 mg/lb) PO/IV/IM/SC q3-4h prn; not to exceed adult dose
Contraindications Documented hypersensitivity; MAOIs; upper airway obstruction or significant respiratory depression; during labor when delivery of premature infant is anticipated
Interactions Monitor for increased respiratory and CNS depression with coadministration of cimetidine; hydantoins may decrease effects; avoid with protease inhibitors
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Pregnancy category D in prolonged use or high doses at term; caution in patients with head injuries because may increase respiratory depression and CSF pressure (use only if absolutely necessary); use caution postoperatively and in patients with history of pulmonary disease (suppresses cough reflex); increased dosing levels, because of tolerance, may aggravate or cause seizures (even without prior history); adjust dose in patients with renal insufficiency (do not use in patients severe renal dysfunction); normeperidine metabolite accumulation may induce CNS toxicity; monitor closely for morphine-induced seizure activity if prior seizure history
Drug Name
Hydrocodone and acetaminophen (Vicodin, Lortab 5/500, Lorcet-HD) -- Drug combination indicated for moderate to severe pain.
Each tab/cap contains 5 mg hydrocodone and 500 mg acetaminophen.
Adult Dose 1-2 tab/cap PO q4-6h prn
Pediatric Dose <12 years: 10-15 mg/kg/dose acetaminophen PO q4-6h prn; not to exceed 2.6 g/d acetaminophen
>12 years: 750 mg acetaminophen PO q4h; not to exceed 10 mg hydrocodone bitartrate per dose or 5 doses per 24 h
Contraindications Documented hypersensitivity; high-altitude cerebral edema (HACE); elevated intracranial pressure (ICP)
Interactions Coadministration with phenothiazines may decrease analgesic effects; toxicity increases with CNS depressants or tricyclic antidepressants
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Tab contains metabisulfite, which may cause hypersensitivity; caution in patients dependent on opiates because this substitution may result in acute opiate withdrawal symptoms; caution in severe renal or hepatic dysfunction
Drug Name
Oxycodone and acetaminophen (Percocet, Tylox, Roxicet) -- Drug combination indicated for relief of moderate to severe pain.
Each tab/cap contains 5 mg oxycodone and 325 mg acetaminophen.
Adult Dose 1-2 tab/cap PO q4-6h prn
Pediatric Dose 0.05-0.15 mg/kg/dose oxycodone PO; not to exceed 5 mg/dose of oxycodone PO q4-6h prn
Contraindications Documented hypersensitivity
Interactions Phenothiazines may decrease analgesic effects; toxicity increases with coadministration of CNS depressants or tricyclic antidepressants
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Duration of action may increase in elderly persons; be aware of total daily dose of acetaminophen patient is receiving; not to exceed 4000 mg/24h of acetaminophen; higher doses may cause liver toxicity
FOLLOW-UP Section 8 of 11
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Further Inpatient Care:


Objectives during inpatient stay include the following:
Correction of fluid and electrolyte abnormalities
Antibiotics for complicating infections
Performing imaging studies as appropriate (eg, ultrasound, HBS)
Cholecystectomy once the patient is stable or percutaneous transhepatic cholecystostomy drainage in unstable high-risk surgical patients
Further Outpatient Care:


In cases of uncomplicated cholecystitis, outpatient treatment may be appropriate. If a patient can be treated as an outpatient, discharge with antibiotics, appropriate analgesics, and definitive follow-up care. Criteria for outpatient treatment include the following:
Afebrile with stable vital signs
No evidence of obstruction by laboratory values
No evidence of common bile duct obstruction on ultrasound
No underlying medical problems, advanced age, pregnancy, or immunocompromised condition
Adequate analgesia
Reliable patient with transportation and easy access to a medical facility
Prompt follow-up care
In/Out Patient Meds:


For outpatient treatment of uncomplicated cholecystitis, the following medicines may be appropriate:
Prophylactic antibiotic coverage with Levaquin (500 mg PO qd) and Flagyl (500 mg PO bid), which should provide coverage against the most common organisms
Antiemetics such as oral/rectal Phenergan or Compazine to control nausea and prevent fluid and electrolyte disorders
Analgesics such as oral Percocet or Vicodin
Transfer:


Consider patient transfer if the following conditions apply:
Appropriate diagnostic resources are not available.
Higher level of care is required.
Surgeons and/or specialists are unavailable.
Deterrence/Prevention:


Prevention of cholecystitis requires cholecystectomy.
In patients who are unstable, percutaneous transhepatic cholecystostomy drainage may be appropriate.
Some studies have shown that daily CCK administration may help prevent acalculous cholecystitis in patients at risk.
Complications:


Bacterial proliferation within the obstructed gallbladder results in empyema of the organ. Patients with empyema may have a toxic reaction and may have more marked fever and leukocytosis. The presence of empyema frequently requires conversion from laparoscopic to open cholecystectomy.
In rare instances, a large gallstone may erode through the gallbladder wall into an adjacent viscus, usually the duodenum. Subsequently, the stone may become impacted in the terminal ileum or in the duodenal bulb and/or pylorus, causing a gallstone ileus.
Emphysematous cholecystitis occurs in approximately 1% of cases and is noted by the presence of gas in the gallbladder wall from the invasion of gas-producing organisms such as E coli, Clostridia perfringens, and Klebsiella species. This complication is more common in patients with diabetes, has a male predominance, and is acalculous in 28% of cases. Because of a high incidence of gangrene and perforation, emergency cholecystectomy is recommended.
Sepsis
Pancreatitis
Perforation occurs in up to 15% of patients.
Prognosis:


For uncomplicated cholecystitis, the prognosis is excellent, with a very low mortality rate.
In patients who are critically ill with cholecystitis, the mortality rate approaches 50-60%, especially in the setting of gangrene or empyema.
Once complications such as perforation/gangrene develop, the prognosis becomes less favorable. In patients who are critically ill with acalculous cholecystitis and perforation or gangrene, the mortality rate can be as high as 50-60%.
Patient Education:


Patients diagnosed with cholecystitis must be educated regarding causes of their disease, complications if left untreated, and medical/surgical options to treat cholecystitis.
For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center. Also, see eMedicine's patient education articles Gallstones and Pancreatitis.
MISCELLANEOUS Section 9 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography




Medical/Legal Pitfalls:


Delays in making the diagnosis of acute cholecystitis result in a higher incidence of morbidity and mortality. This is especially true for ICU patients who develop acalculous cholecystitis. The diagnosis should be considered and investigated promptly in order to prevent poor outcomes.
Special Concerns:


Pregnancy
RUQ pain in pregnancy can be related to a number of different diagnoses, including preeclampsia, appendicitis, and cholelithiasis.
These patients must have a thorough examination because complications can arise quickly and can be life threatening to both the mother and the unborn child.
Although laparoscopic cholecystectomy is considered safest during the second trimester, it has been performed successfully during all trimesters.
Elderly patients (especially patients with diabetes) may present with vague symptoms and without many key historical and physical findings. Elderly patients may also progress to complicated cholecystitis rapidly and without warning.
The pediatric population may also present without many of the classic findings. Children who are at higher risk for developing cholecystitis include patients with sickle cell disease, seriously ill children, those on prolonged TPN, those with hemolytic conditions, and those with congenital and biliary anomalies.
Patients who are immunocompromised are at increased risk of developing cholecystitis from a number of different infectious sources.