Pediatric Cholecystitis 

Updated: Oct 20, 2017
Author: Steven M Schwarz, MD, FAAP, FACN, AGAF; Chief Editor: Carmen Cuffari, MD 

Overview

Background

Cholecystitis is defined as inflammation of the gallbladder and is traditionally divided into acute and chronic subtypes. These subtypes are considered to be two separate disease states; however, evidence suggests that the two conditions are closely related, especially in the pediatric population.

Most gallbladders that are removed for acute cholecystitis show evidence of chronic inflammation, supporting the concept that acute cholecystitis may actually be an exacerbation of chronic distension and tissue damage. Cholecystitis may also be considered calculous or acalculous, but the inflammatory process remains the same.

Cholecystitis, which has long been considered an adult disease, is quickly gaining recognition in pediatric practice because of the significant documented increase in nonhemolytic cases over the last 20 years. Gallbladder disease is common throughout the adult population, affecting as many as 25 million Americans and resulting in 500,000-700,000 cholecystectomies per year (see Epidemiology). The image below illustrates the technique for laparoscopic cholecystectomy.

Diagram illustrating the technique for laparoscopi Diagram illustrating the technique for laparoscopic cholecystectomy. The gallbladder is retracted with grasping 5-mm laparoscopic instruments, and clips are applied over the cystic duct and artery.

Although gallbladder disease is much rarer in children, with 1.3 pediatric cases occurring per every 1000 adult cases, pediatric patients undergo 4% of all cholecystectomies. In addition, acalculous cholecystitis, uncommon in adults, is not that unusual in children with cholecystitis.

Because of the increasing incidence of gallstones and the disproportionate need for surgery in the pediatric population, consider cholecystitis and other gallbladder diseases in the differential diagnosis in any pediatric patient with jaundice or abdominal pain in the right upper quadrant, particularly if the child has a history of hemolysis (see Presentation).

Cholelithiasis is the most common cause of acute or chronic cholecystitis in adults and children. (See Etiology)

Abdominal ultrasonography has become the diagnostic tool of choice in evaluating cholelithiasis, although it is less accurate in cholecystitis (see Workup). Cholecystectomy is the standard of care for cholecystitis. Medical treatment is used in patients who are not candidates for surgery, as well as in certain other settings (see Treatment).

Types of Gallstones

Three major types of gallstones may form in cholelithiasis: cholesterol, pigment, or brown. However, most gallstones have components of more than one type.

Cholesterol gallstones (shown below) are radiolucent and are composed of cholesterol (>50%), calcium salts, and glycoproteins. They form within the gallbladder and migrate to the bile duct.

Photograph of a gallbladder filled with numerous s Photograph of a gallbladder filled with numerous small cholesterol stones.

Pigment gallstones are black, often radiopaque, and are usually associated with hemolytic diseases. Radiopacity and color are related to an increased concentration of calcium bilirubinate, which interacts with mucin glycoproteins to form gallstones. These gallstones also form within the gallbladder and migrate to the ductal system.

Brown gallstones, in contrast, form within the ductal system and are orange, soft, and greasy. They are composed of calcium salts of bilirubin, stearic acid, lecithin, and palmitic acid. These gallstones are more often associated with infection.[1]

Go to Cholecystitis and Acalculous Cholecystitis for more complete information on these topics.

Pathophysiology

Distinct complications can occur at any point in the course or treatment of gallbladder disease. They can be divided into complications of gallstones, inflammation, and treatment. At any of the 3 stages, disease may exacerbate preexisting medical conditions, leading to cardiac, hepatic, pulmonary, or renal demise.

Gallstones may cause obstruction of the common bile duct, acute or chronic cholecystitis, cholangitis, gallbladder perforation, or pancreatitis. Choledocholithiasis occurs less often in children. Risk increases with age. Nevertheless, obstruction of the common bile duct may still accompany pediatric cholelithiasis, especially in the presence of congenital ductal narrowing or stenosis, and it may cause hepatocyte damage. Rule out common bile duct stones in the presence of any jaundice.

Stones may also perforate the gallbladder, allowing bile leakage into the peritoneum, or create a cystoenteric fistula, possibly leading to a gallstone ileus.

The most common complication of gallstones in children is pancreatitis, reported to occur in 8% of cases. The course is usually mild and resolves spontaneously with passage of the stone, which occurs in several days.

Acute infection and inflammation of the gallbladder or ductal system may lead to sepsis or local spread of disease. Perforation, abscess, empyema, infarction, or gangrene may develop in acute cholecystitis, causing peritonitis and threatening the patient's life. Chronic cholecystitis may lead to acute hydrops, acute cholecystitis, or, more insidiously, porcelain gallbladder.

The well-known radiographic finding of porcelain gallbladder is caused by chronic calcium deposition in the wall of the gallbladder as a result of inflammation. Although early studies reported a 12-60% incidence of carcinoma arising in the gallbladder wall of patients with porcelain gallbladder, more recent data suggest that the cancer risk is significantly lower (approximately 7% in one large series).[2]

Etiology

This subsection will discuss the etiology of cholecystitis and of gallstones.

Chronic Cholecystitis

Chronic cholecystitis is most often related to gallstone disease but has been documented without gallstones. Its course may be insidious or involve several acute episodes of obstruction. The initiating factor is thought to be the supersaturation of bile, often with cholesterol crystals and/or calcium bilirubinate, which contributes to stone formation and inflammation.

These processes lead to chronic obstruction, decreased contractile function, and biliary stasis, which contribute to further inflammation of the gallbladder wall. Biliary stasis also permits the increased growth of bacteria, usually Escherichia coli and enterococci, which may irritate the mucosa and increase inflammatory response.

Chronic acalculous cholecystitis is less understood, but it may result from a functional deficiency of the gallbladder, which leads to spasm and an inability to appropriately empty the gallbladder contents, causing chronic bile stasis.

Acute Cholecystitis

Acute calculous cholecystitis results from a more sudden obstruction of the cystic duct by gallstones, which causes distension of the sac, edema, and bile stasis with bacterial overgrowth. These events lead to inflammation and a local release of lysolecithins, which further exacerbates the inflammatory process. In addition, edema of the wall and duct reinforces obstruction and may cause ischemia of the local tissue, with the release of still more inflammatory mediators.

Local lymph node hypertrophy and duct torsion or congenital anomalies may further complicate the obstructive process. As obstruction and inflammatory tissue damage progress, bacteria may proliferate. Bile cultures are positive in 75% of cases, usually with E coli, enterococci, or Klebsiella species. Bacterial infection most likely follows tissue damage, but after colonization, the severity of the disease can dramatically worsen. This cascade of events quickly leads to pain and, possibly, a toxic appearance.

Acute acalculous cholecystitis develops in a similar manner but from different etiologic factors than acute calculous cholecystitis does. Acute acalculous cholecystitis is most often associated with systemic illness, whether chronic or critical and acute. Increased mucus production, dehydration, and increased pigment load all increase cholesterol saturation and biliary stasis, whereas hyperalimentation, assisted ventilation, intravenous narcotics, ileus, and prolonged fasting contribute to cholestatic hypofunction.

These conditions allow the formation of biliary sludge and may lead to obstruction. The resulting inflammation and edema lead to compromised blood flow and bacterial infection, as in acute calculous cholecystitis; however, the compromised blood flow appears more central in acute acalculous cholecystitis because acute acalculous cholecystitis can occur in vasculitides (eg, Kawasaki disease, periarteritis nodosa), presumably because of direct vascular compromise.

Common Causes of Gallstones

All gallstones require similar conditions to form. First, the bile must be supersaturated either by cholesterol or by bilirubin. Second, chemical kinetics must favor nucleation of cholesterol. This occurs when cholesterol is no longer soluble in bile. Finally, stasis of the gallbladder allows cholesterol or calcium bilirubinate crystals to remain long enough to aggregate to form gallstones.

Many disease processes can precipitate or foster these events. Infection induces the deconjugation of bilirubin glucuronide, thereby increasing the concentration of unconjugated bilirubin in the bile. Hemolysis overwhelms the conjugation abilities of the liver, increasing the amount of unconjugated bilirubin in the bile. Hemolytic diseases include hereditary spherocytosis, sickle cell disease, thalassemia major, hemoglobin C disease, and possibly uncontrolled glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Multiple blood transfusions also increase the pigment load. This predisposes the bile to the formation of biliary sludge.

Dehydration concentrates the bile, thereby increasing viscosity and stone formation. Cystic fibrosis (CF) is associated with increased mucus production and may cause a similar scenario.

In rural Asia, infections with Clonorchis sinensis (also called Opisthorchis sinensis) or Ascaris lumbricoides are predisposing conditions for brown gallstones. In the United States, these gallstones are more rare, although they have been found after cholecystectomy in which the bile was infected (most often by E coli) and in infants and children infected with Staphylococcus, Enterobacter, Citrobacter, and Salmonella species.

Chronic urinary tract infections may also predispose individuals to the formation of brown gallstones. Isolated gallstones associated with Ascaris have been recorded in the United States.[3]

Unusual Causes of Gallstones

Gallstones may also be caused by medications. Octreotide, ceftriaxone,[4, 5] cyclosporine,[6] and furosemide[7] have all been associated with gallstone disease. Ceftriaxone causes a reversible pseudolithiasis through several mechanisms. Ceftriaxone displaces bilirubin on albumin, thereby increasing the blood concentration of unconjugated bilirubin. Ceftriaxone is also secreted in bile, and calcium salts of ceftriaxone have been found in biliary sludge.

Cyclosporine may be lithogenic, but it seems to require high drug levels and hepatotoxicity. Furosemide has also been implicated in gallbladder disease, but it usually is only a compounding factor in the presence of prematurity, sepsis, or small-bowel disease.

Finally, ileal disease or resection has been correlated with cholelithiasis in adults and children, although the risks associated with resection seem to be highest after puberty.[8] These patients have an increased cholesterol secretion and a lowered bile acid secretion, which leads to cholesterol supersaturation.

Acalculous Cholecystitis

The aforementioned diseases may also contribute to the development of acalculous cholecystitis, because the formation of gallstones is not necessary for the obstruction of the bile duct. In addition, acalculous cholecystitis has been heavily associated with local inflammation, endocarditis, vasculitides, and systemic infection.

Implicated infections include those occurring in typhoid fever, scarlet fever, measles, and acquired immunodeficiency syndrome (AIDS), as well as infections caused by Mycoplasma, Streptococcus (groups A and B), and gram-negative organisms, such as Shigella and E coli.

Acalculous cholecystitis may also occur postoperatively. Tsakayannis et al observed acute cholecystitis occurring after open-heart surgery in 4 of their patients, although it is more commonly observed in other nonbiliary surgeries and trauma.[9]

Shock, sepsis, hyperalimentation, prolonged fasting, intravenous narcotics, and multiple transfusions are common risk factors for the development of acute acalculous cholecystitis. The presence of 4 or more of these risk factors has been associated with a strong predisposition to the disorder.

Risk Factors for Cholelithiasis

Cholelithiasis in infancy is most often related to acute and chronic illness and hyperalimentation.[10] More specifically, risk factors include abdominal surgery, sepsis, bronchopulmonary dysplasia, hemolytic disease, malabsorption, necrotizing enterocolitis, and hepatobiliary disease. Other factors implicated include CF, polycythemia, phototherapy, and distal ileal resection.

The immature hepatobiliary system of infants may predispose them to stone formation. Decreased hepatobiliary flow and immature bilirubin conjugation contribute to stasis and sludge formation. Interestingly, as much as one half of infantile gallstones, especially those associated with hyperalimentation, may resolve spontaneously.

In a review of 693 cases of pediatric cholelithiasis by Friesen et al, infants with the disease tended to be ill and receiving hyperalimentation, and had prematurity, congenital anomalies, and necrotizing enterocolitis as compounding risk factors.[11]

Risk factors for cholelithiasis in children include hepatobiliary disease, abdominal surgery, artificial heart valves, and malabsorption. Gallstones usually contain a mixture of calcium bilirubinate and cholesterol. Hemolysis and prolonged hyperalimentation are significant influences in this age group. (In the Friesen study, hemolysis was the most common underlying condition for cholelithiasis in children aged 1-5 years).

In adolescents, risk factors for cholelithiasis include pregnancy, hemolytic disease, obesity, abdominal surgery, hepatobiliary disease, hyperalimentation, malabsorption, dehydration, and the use of birth control pills.

In addition, early menarche has been shown to significantly increase the incidence of cholecystitis, perhaps because of the lithogenic effect of estrogen on bile. Racial and genetic influences in the adolescent age group are similar to those in adults (see Epidemiology).

Epidemiology

In adolescence, differences in the frequency of cholecystitis based on race, genetics, and sex become more evident. Adolescent girls are much more at risk of developing the disease than boys are. The female-to-male ratio in white adults is 4:1; in adolescents, the ratio is estimated to be 14-22:1.

United States Statistics

The exact frequency of acute and chronic cholecystitis in children is not known. The overall incidence appears to have increased in the last 3 decades because of the high consumption of fatty foods by young children (ie, Western diet). In children with chronic hemolysis (eg, hemolytic anemias), the incidence of cholecystitis is much higher than in the general population. Biliary sludge and/or gallstones are likely to form in 1 in 5 children with hemolytic anemia before their adolescent years.

Racial Differences in Incidence

Racial and genetic influences in the adolescent age group are similar to those of adults. African Americans (without hemolytic disease) and the African Masai are less prone to cholelithiasis, whereas Chilean women, Pimas,[12] and whites are more predisposed to this disease.

Two contributing diseases in particular have a genetic component and racial distribution. Hemolytic diseases, including sickle cell disease and hemoglobin C disease, occur almost exclusively in the black population, although thalassemia also has a Mediterranean distribution. CF, which occurs mainly in whites, may also contribute to the formation of biliary sludge and, possibly, acalculous cholecystitis.

Age Differences in Incidence

In the previously mentioned Friesen review of 693 cases of pediatric cholelithiasis, 10% of gallstones were found in children younger than age 6 months, 21% were found in children aged 6 months to 10 years, and 69% were found in persons aged 11-21 years.[11]

Prognosis

Isolated cholecystitis generally has an excellent prognosis if diagnosed and treated appropriately. Children can be expected to return to presurgical functioning soon after cholecystectomy, especially after a laparoscopic procedure. The greatest indicator for poor prognosis is the underlying disease process itself. Cholecystitis that is treated is usually well tolerated.

Children can be expected to do well, although comorbid conditions are common and may cause complications. Risk factors for morbidity and mortality in the pediatric population include associated conditions, such as cystic fibrosis (CF), obesity, hepatic disease, diabetes mellitus, sickle cell disease, and immunocompromise.

Complications That May Influence Prognosis

General complications, such as pulmonary, cardiac, thromboembolic, hepatic, and renal insufficiency, account for most deaths. Procedure-related complications mainly contribute to morbidity and occur with higher frequency in acute cholecystitis in which symptoms of gallstone disease have been present longer than 1 year. Procedure-related complications are predictable and include hemorrhage, bile duct injury, ileus, pancreatitis, and leakage from the newly created stump. Risks from anesthesia are also noted. In addition, wound infections, abscess, or cholangitis may complicate the postoperative course.

Mortality Rates for Calculous and Acalculous Cholecystis

Most of the data on morbidity and mortality in gallstone disease is derived from the adult population, although some trends can be extracted and applied to the pediatric population. In general, the mortality rate of cholecystectomy in acute cholecystitis has dropped from 6.6% in 1930 to 1.8% in 1950 to nearly 0% in later studies. In one study, the overall mortality rate in 42,000 patients undergoing open cholecystectomy was 0.17%; the mortality rate in patients younger than 65 years was 0.03%.

Acalculous cholecystitis has its own statistics for mortality and morbidity. Mortality in the adult population has been reported to be as high as 10%, and in patients with critical illness, the mortality rate can reportedly reach 50%. The mortality rate in patients with critical illness is most likely related to the close association with severe systemic illness. Concomitant illness and risk factors should be considered when predicting morbidity and mortality in children.

Patient Education

Patient education can be focused on prevention, observation, timely treatment, and information about the intraoperative procedure. Preventive measures include diet and weight management. In addition, educate patients with CF about compliance with pancreatic enzyme and bile acid supplementation.

At-risk patients, whether because of chronic disease of cultural and/or genetic risk factors, should be aware of signs and symptoms of cholecystitis and gallstone disease. This enables them to seek timely medical attention and avoid complications of acute cholecystitis. Finally, educate all patients undergoing operative procedures about preoperative and postoperative care and the expectations and risks of surgery.

For patient education information, see eMedicineHealth's Digestive Disorders Center and Cholesterol Center, as well as Gallstones.

 

Presentation

History

Symptoms of cholelithiasis often precede those of cholecystitis, although patients may have acute cholecystitis on initial presentation. Cholelithiasis causes biliary colic. Patients may complain of intermittent abdominal pain of inconsistent severity in the right upper quadrant, with possible radiation to the scapular region of the back, or pain may be diffuse or localized to the epigastrium.

Discomfort is more likely to be nonspecific in infants and younger children. Patients of this age group often present with irritability, jaundice, and acholic stools.

The classic history of patients with gallstones is postprandial right upper quadrant pain associated with nausea and vomiting, but this is usually observed only in older children. Jaundice in pediatric cholelithiasis is much more frequent than in adults and can occur in the absence of gallstone obstruction of the common bile duct. Most likely, the stone causes inflammation of the ductal tissue, creating an edematous obstruction to bile flow.

Patients with chronic cholecystitis usually present similarly to patients with biliary colic, with an intermittent and indolent history of pain. Therefore, differentiation must be made on the basis of findings from the physical examination and diagnostic tests.

Acute cholecystitis pain resembles biliary colic but is usually more severe and constant, lasting for several days. The pain may begin as a vague discomfort; however, as inflammation spreads and affects the surrounding peritoneum, the pain localizes to the right upper quadrant.

Patients often report a recent history of nausea, vomiting, anorexia, and a low-grade fever. Onset of symptoms usually occurs approximately 1 week prior to presentation, although the patient may report years of the less severe symptoms of biliary colic and chronic cholecystitis.

Physical Examination

The physical examination in acute cholecystitis usually reveals right upper quadrant tenderness. The classic triad is right upper quadrant pain, fever, and leukocytosis. The patient may have abdominal guarding and a positive Murphy sign (ie, arrest of inspiration on deep palpation of the gallbladder in the right upper quadrant of the abdomen). Omental adherence to the inflamed gallbladder combined with distension may create a palpable mass between the 9th and 10th costal cartilages.

The ductal system may become inflamed, causing cholangitis. In 50% of these cases, the examiner may find a Charcot triad. This combination of right upper quadrant pain, fever, and jaundice indicates obstruction of the common bile duct and the presence of acute cholangitis. The Charcot triad is considered to represent a medical emergency, and patients require immediate intervention.

Performing a physical examination may be the only way to distinguish biliary colic from chronic cholecystitis. In chronic cholecystitis, the patient usually complains of tenderness to palpation in the right upper quadrant; however, the differentiation may be trivial, given the high likelihood of chronic cholecystitis in the presence of recurring biliary colic.

 

DDx

Diagnostic Considerations

The differential diagnosis of cholecystitis is based on the presenting symptom of right upper quadrant abdominal pain. In the pediatric population, consider the following conditions in addition those listed in Differentials:

  • Biliary colic

  • Cholangitis

  • Rupture of the gallbladder

  • Peptic ulcer disease

  • Renal colic

  • Gastritis

  • Pleurisy

  • Fitz-Hugh and Curtis syndrome (gonococcal perihepatitis)

  • Hepatic abscess

  • Abdominal tumor

  • Pyelonephritis

Infants with cholecystitis may present with irritability, jaundice, and acholic stools. Because of young age and differing presentation, consider congenital bile duct anomalies, such as biliary atresia and paucity of intrahepatic bile ducts.

Acalculous cholecystitis usually occurs in children with preexisting systemic illness and, therefore, may be masked by other conditions and analgesics. Be sensitive to the possibility of cholecystitis if systemic infection and multiple risk factors are present.

Differential Diagnoses

 

Workup

Approach Considerations

Plain abdominal radiography may be used for initial screening in patients with abdominal pain. Abdominal ultrasonography has become the diagnostic tool of choice in evaluating cholelithiasis, but it is less accurate in cholecystitis.

Go to Imaging in Acalculous Cholecystitis and Imaging in Acute Cholecystitis for more complete information on these topics.

Laboratory Testing

In assessing for cholecystitis, appropriate laboratory studies include the following blood tests:

  • Complete blood count (CBC)

  • Gamma-glutamyltransferase (GGT)

  • Amylase

  • Direct and indirect bilirubin

  • Alkaline phosphatase

  • Transaminases

In addition, urinalysis should be performed.

In acute cholecystitis, the white blood cell count is elevated, with a predominance of polymorphonuclear cells and bands. Bilirubin, alkaline phosphatase, and GGT levels rise secondary to a blocked biliary system.

The traditional cholestatic picture involves direct hyperbilirubinemia, with a direct-to-indirect ratio approaching 1:1. Amylase may be elevated even in the absence of obstructive pancreatitis. In addition, transaminases may show mild elevation but not a significant increase, unless obstruction has been severe enough to cause hepatocyte damage.

Transaminase levels are more likely to rise early in patients with obstruction of the common bile duct.

Plain Abdominal Radiography

Calcifications representing radiopaque gallstones may be observed in the gallbladder or ductal system. Radiopaque gallstones contain more calcium bilirubinate and are more common in the pediatric population, especially in infants and children. In addition, complications such as porcelain gallbladder and emphysematous cholecystitis may be visible on radiographs, although these complications are rare in children.

Abdominal Ultrasonography

The reliability of ultrasonography for detecting either opaque or lucent gallstones is well established. Results are immediate, and accessibility is usually excellent. The accuracy of abdominal ultrasonography in depicting gallstones is estimated to be more than 95%. However, its reliability in the diagnosis of acute cholecystitis is more limited.

Ultrasonographic findings in acute cholecystitis include a discrete echodensity representing the gallstone, the presence of sludge, and, possibly, ductal anomalies or dilation. The gallbladder may be dilated with thickened walls.

Imhof et al found gallbladder wall thickness of more than 3.5 mm to be a reliable independent diagnostic indicator of cholecystitis.[13]

Gallstones are often in a dependent position in the gallbladder and may move as the patient changes position.

Oral Cystography

Oral cystography has been used in the past, but has been largely abandoned because of the refinement of ultrasonography. Oral cystography involves the ingestion of contrast material that is secreted in the bile. Lack of visualization of the gallbladder indicates cholelithiasis. This procedure is limited by liver dysfunction and malabsorption. In addition, the contrast tablets have been associated with emesis and diarrhea, further complicating effectiveness.

Biliary Scintography

The most accurate tool in the diagnosis of acute cholecystitis is biliary scintiphotography, otherwise known as the hepatic 2,6-dimethyliminodiacetic acid or hepatoiminodiacetic acid (HIDA) scanning.

This procedure involves the intravenous injection of substances labeled with technetium Tc 99m (99m Tc), taken into the hepatocytes, and excreted into the biliary system. Normal hepatic uptake without gallbladder visualization is diagnostic, but false-positive results occur with decreased biliary function secondary to prolonged fasting and the use of hyperalimentation. Morphine augmentation of this test has been shown to decrease false positive results.

Induced spasm of the sphincter of Oddi increases biliary pressure and enhances gallbladder filling. This test may be unnecessary, however, because the clinical diagnosis and treatment are determined by the symptoms and presence of gallstones or sludge.

Ultrasonography has proved its usefulness in depicting gallstones, does not rely on contrast, and, therefore, may be safer.

Magnetic Resonance Cholangiopancreatography

Magnetic resonance cholangiopancreatography (MRCP) scanning can be used in the diagnosis of cholecystitis, especially in cases in which ultrasonography is not helpful.

Ultrasonographic results may be compromised by ileus, surgical incisions, and coexisting diseases, especially those in patients who are critically ill. MRCP may be more sensitive than ultrasonography in detecting inflammation within and around the gallbladder, as well as within the biliary tree. Although frequently used in the past, CT scanning is not generally recommended in pediatric patients because of the associated extensive radiation exposure.

Endoscopic Retrograde Cholangiopancreatography

If the patient displays signs and symptoms of choledocholithiasis, endoscopic retrograde cholangiopancreatography (ERCP) may be used preoperatively for exploration of the common bile duct. This procedure generally follows identification of common duct stones, either by ultrasound or by MRCP scanning. ERCP is both diagnostic and therapeutic, because it may be used for stent placement, basket retrieval, or papillotomy to allow passage of gallstones; however, available choledochoscopes may be too large for small patients.

Choledocholithiasis complicates the picture of cholecystitis and usually requires adjunctive procedures to cholecystectomy. If obstruction of the common bile duct is suspected preoperatively, perform ERCP before surgery with papillotomy, stent placement, or basket retrieval.

If gallstones are found intraoperatively, several techniques can be used. The common bile duct can be flushed with saline or opened and explored. Additionally, an endoscope or nephroureteroscope may be used intraoperatively for basket retrieval.

Endoscopic extraction of a cholesterol stone is demonstrated in the image below.

Photograph illustrating the role of endoscopic ret Photograph illustrating the role of endoscopic retrieval of common bile duct stones. The picture shows a balloon placed via the endoscope into the ampulla for extraction of a cholesterol stone that was occluding the common bile duct.

Endoscopic Ultrasonography

In adult studies of suspected choledocholithiasis, the emerging technique of endoscopic ultrasonography (EUS) has been shown to detect more than 90% of common bile duct stones. This diagnostic modality is of particular use in patients with recurrent gallstone pancreatitis. In one study, EUS was able to detect stones in 77% of patients in whom CT scanning, standard biliary tract ultrasound, and/or ERCP findings were negative.[14] .

In patients with acute pancreatitis, the sensitivity and specificity of this procedure are approximately 98%. Where EUS is not available or feasible (eg, in young children), MRCP (discussed above) is also a highly sensitive and specific modality. In fact, a 2015 Cochrane Review showed both EUS and MRCP have high diagnostic accuracy for detection of common bile duct stones.[15]  Because these studies demonstrate similar diagnostic accuracy, the choice of study (particularly in children) often depends on availability.

Cholecystokinin Stimulation

Cholecystokinin (CCK) stimulation may be used during other imaging studies, such as cholescintigraphy. Gallbladder dyskinesia after CCK administration is diagnostic of gallbladder hypofunction and may be useful in discerning acalculous or chronic cholecystitis and acute inflammation.

Histologic Findings

The histology of the inflamed gallbladder is fairly straightforward.

Acute cholecystitis causes changes similar to those of any acute inflammation. Edema, leukocytic infiltration, and vascular congestion are prominent. Inflammation may progress to abscess formation, gangrenous necrosis, and perforation, especially in acalculous cholecystitis.

Chronic cholecystitis produces long-term inflammatory changes, with lymphocytes, plasma cells, and macrophages scattered throughout the mucosa. Subserosal fibrous tissue forms and may extend into the subepithelial layer with increasing disease severity. As the mucosa proliferates, epithelium may become buried in crypts known as Rokitansky-Aschoff sinuses.

Over time, chronic obstruction and inflammation may lead to the deposit of calcium within the gallbladder wall, causing the porcelain gallbladder, which is visible on flat plate imaging of the abdomen. Another variation is xanthogranulomatous cholecystitis, in which chronic inflammation leads to a shrunken, nodular gallbladder with many foci of necrosis and hemorrhage. This condition may be confused with malignancy but is actually benign.

Hydrops of the gallbladder may also develop with chronic obstruction. This is characterized by a distended lumen and atrophic walls. Obstruction of the common bile duct may cause histologic change in nearby organs. Ductal hyperplasia ensues from obstruction and distension, and periportal fibrosis in the liver may occur with hepatic bile flow obstruction. Gallstones may also cause transient acute pancreatitis, resulting in characteristic histologic changes in the pancreas.

 

Treatment

Approach Considerations

Cholecystectomy is the standard of care for cholecystitis. Medical treatment is used in patients who are not candidates for surgery, as well as in certain other settings. Intervention with cholecystotomy or ERCP may be indicated.

Although controversy still surrounds the use of cholecystectomy versus medical management, the morbidity and mortality rates have been the same in patients receiving early surgery as in those in whom surgery was delayed more than 48 hours for stabilization of inflammation. However, because symptoms continued in 24% of patients in whom surgery was delayed, if surgery is the goal of treatment, no advantage to delaying surgery is noted.

Conservative Therapy

Removal of the gallbladder is the standard of care in patients with symptomatic gallstone disease, although some exceptions are noted.

Acute Cholecystitis

Critically ill children with acute acalculous cholecystitis may not tolerate anesthesia and operative conditions. These children should receive antibiotic therapy, parenteral nutrition, and gastric decompression until their condition improves. These patients may then undergo surgery if symptoms persist; however, many cases resolve with medical therapy alone.

One author reported a 75% resolution of acute acalculous cholecystitis with the use of antibiotics, nasogastric suction, and hyperalimentation. Therefore, antibiotics may be sufficient in critically ill patients who do not tolerate anesthesia and who may be assisted by other procedures, such as cholecystotomy, if gallbladder drainage is necessary.

Observation is also recommended for infants with gallstones, including for those with parenteral nutrition–associated cholestasis and for infants in whom gallstones are incidentally noted. These gallstones often dissolve with maturation of the hepatobiliary system.

The gallbladder should be removed if the patient shows any sign of common duct obstruction, pancreatitis, or cholecystitis. Cholecystectomy should also be performed if gallstones persist longer than 1 year or if long-term hyperalimentation is anticipated, as in Crohn disease, pseudo-obstruction, or short-bowel syndrome.

Chronic Cholecystitis

Medical care in chronic cholecystitis or other gallbladder disease is also supportive. Cholecystectomy is recommended in most patients with gallstone disease. Treatment should be aimed at control of any underlying conditions and preparation for surgery.

Contact Dissolution and Biliary Lithotripsy

Other medical management strategies include contact dissolution and biliary lithotripsy.

Percutaneous transhepatic cholecystolitholysis involves the injection of a cholesterol solubilizer, such as methyl-tert -butyl ether, directly into the gallbladder. The time between instillation and aspiration must be conscientiously limited to avoid leakage into the bile duct, causing abdominal pain and duodenitis. This method has been successful in a few children.

Biliary lithotripsy has also been used with limited success. Similar to lithotripsy for nephrolithiasis, biliary lithotripsy uses shock waves to pulverize gallstones. Biliary lithotripsy causes fragmentation of stones in most patients but rarely causes complete dissolution. Because fragments may still cause biliary colic and cholecystitis, additional oral therapy may be necessary.

All management techniques that involve leaving the gallbladder in situ have 1-year recurrence rates of approximately 10% and 5-year recurrence rates of approximately 50%.

Bile Acid Therapy

Two oral medications that have been used with some success for the dissolution of cholesterol gallstones are chenodiol (chenodeoxycholic acid) and ursodiol (ursodeoxycholic acid). Both medications selectively inhibit hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), thereby decreasing bile cholesterol supersaturation and lithogenicity.

Chenodiol was shown to achieve complete dissolution of pure cholesterol gallstones in 15% of adult patients and partial dissolution in 28% of adult patients. However, the medications are expensive and cause adverse effects, including diarrhea and hepatotoxicity. These agents have not yet been approved by the US Food and Drug Administration (FDA) for use in children.

Combination treatment may be more effective and allow lower doses of each medication, causing fewer adverse effects. Although ursodiol was found to be unsuccessful in dissolving radiolucent gallstones in 10 children with CF, it has been shown to increase hepatobiliary excretion and may be useful in a cytoprotective and preventative role.

Preparation for Surgery

Medical care of the patient with acute cholecystitis centers on stabilization of the patient and preparation for surgery if the patient is a candidate.

The patient should receive nothing by mouth (NPO), and a nasogastric tube should be placed to low-intermittent wall suction for evacuation of gastric contents. This step minimizes stimulation to the inflamed gallbladder and prepares the patient for general anesthesia. Administer pain medications; however, avoid morphine because of its spasmodic effects on the sphincter of Oddi.

Hydration

Administer intravenous (IV) fluids to correct any dehydration and continue as maintenance therapy. Standard regimens include 5% dextrose in 0.2% sodium chloride solution or 5% dextrose in 0.45% sodium chloride solution with 20 mEq of potassium chloride (KCl) per liter at a rate determined by standard pediatric calculations.

Patients who are at risk for vaso-occlusion, including those with sickle hemoglobinopathies, should receive hydration at 1.5 times maintenance dose.

Antibiotic Therapy

Antibiotics with biliary excretion covering enteric pathogens may be administered to control infection. The combination of ampicillin, gentamicin, and clindamycin is a common and well-accepted regimen.

The use of antibiotics remains controversial. Some authors assert that antibiotics are not necessary in simple cases and should be reserved for persistent fever or worsening condition.

However, Agrawal et al found a significant reduction in postoperative infection with the use of prophylactic preoperative antibiotics in elective cholecystectomy.[16]

Because of the high percentage of cases of acute cholecystitis that are complicated by bacterial colonization, clinicians should maintain a low threshold for the use of antibiotic therapy.

Concomitant Sickle Cell Disease

Children with sickle cell disease present a unique challenge, because their hemoglobinopathy may cause perioperative and postoperative complications. These patients are susceptible to vaso-occlusive crises, pneumonia, sepsis, and pulmonary infarct, most likely secondary to hypoxia, dehydration, and acidosis in response to anesthesia.

Nevertheless, elective LP may be safely performed in children with sickle cell disease.[17]

Ware et al observed no complications when preoperative transfusions of packed red blood cells were given to obtain a hemoglobin A ratio greater than 2:1 while the hematocrit level was maintained at 35-45%.[18] This required 2 transfusions given 2 weeks apart in most patients, with partial volume exchange used for those with hemoglobin sickle cell or sickle beta-thalassemia disease.

Cholecystectomy

Although open cholecystectomy (OC) was previously considered the criterion standard, laparoscopic cholecystectomy (LC) is now accepted as the criterion standard and preferred procedure in almost all cases.

Advantages of the laparoscopic approach include reduced pain and hospital stay and improved cosmetic results and patient satisfaction.

Lugo-Vicente found that the length of stay, days that pain medication is taken, and time before a regular diet can be resumed were all reduced by one half with LC.[19]

Some concern remains regarding the previously reported higher risk of bile duct injury. However, the incidence of complicated gallstone disease appears less common in the pediatric population than in the adult population, because most children present with symptomatic cholelithiasis without active inflammation. Consequently, the rate of ductal complications is very low.

Acute inflammation of the gallbladder has been a concern, but many authors now agree that acute cholecystitis is not a contraindication; however, the surgeon must be experienced and well skilled with laparoscopic techniques. In addition, conversion to OC can always be performed in difficult cases.

Some authors assert that LC is ideal in infants and children and should be the procedure of choice. In this case, surgical experience with laparoscopy and with infants is essential. Wide spacing of cannulas is helpful in small children to allow for visualization and adequate working distance. Also, with conscientious surgical technique, some authors believe that bile duct injury can be minimized.

In general, OC is reserved for conversion and cases of prior major abdominal surgery. OC is accomplished through a right subcostal incision or a transverse abdominal incision if a splenectomy is also indicated. Laparoscopic entry involves 4 ports: 2 subcostal, 1 subxiphoid, and 1 umbilical.

The surgical course is usually routine. Patients can be admitted to the hospital the day of surgery and discharged within 48-72 hours. The average postsurgical hospital stay after LC is 36 hours, whereas patients undergoing OC typically need to stay in the hospital for 3 days.

Continue hydration until the patient can tolerate a regular diet, usually the morning after LC. In either procedure, it is recommended to observe the patient postoperatively for complications, including fever, jaundice, ileus, pancreatitis, bile leak, or urinary retention. Jaundice or continued right upper quadrant pain may signify a retained common duct stone or biliary injury and should be investigated using ERCP or hepatoiminodiacetic acid (HIDA) scanning as soon as possible.

Technique for Laparoscopic Cholecystectomy in Children

The technique for laparoscopic cholecystectomy in pediatric patients is very similar to the one described in adult patients; however, a few variables must be considered.[20, 21, 22]

First, the trocar placement (demonstrated in the image below) is determined by patient size and position of the gallbladder and the liver.

Operative photograph illustrating the position of Operative photograph illustrating the position of small (5 mm, 10 mm) trocars in the abdomen of a 12-year-old child undergoing laparoscopic cholecystectomy. By using this technique, the surgeon can avoid large incisions and remove the gallbladder safely.

The authors usually start by placing a 12-mm trocar in the umbilical position. A small incision is made from the center of the umbilicus inferiorly, in order to expose the midline fascia at the umbilicus. Local anesthetic is infiltrated at that site.

The authors' preferred approach is to place a STEP trocar (Covidien Surgical; Mansfield, MA) through that site using a Verees needle technique. Starting with a 5-mm STEP trocar is recommended; once the peritoneal cavity is insufflated with carbon dioxide, the trocar is upgraded to a 12-mm STEP placed through the same sleeve as the 5-mm trocar.

Typically, the peritoneal cavity is insufflated with carbon dioxide using the following pressure limits:

  • Obese teenaged patients - 16 mm Hg

  • Normal-sized, healthy teenaged patients - 14 mm Hg

  • Patients aged 8-12 years - 12 mm Hg

  • Patients younger than 7 years - 10 mm Hg

If the patient had any previous abdominal surgery or is significantly obese, the authors prefer to use an open technique for the initial trocar placement. In such cases, creating an opening on the inferior aspect of the umbilicus until the muscle fascia and the linea Alba can be visualized is important.

Stay sutures of 2-0 Vicryl are placed on each side of the muscle fascia, which is then opened under direct visualization. Additional Vicryl sutures may be needed in order to elevate the fascia until the peritoneal membrane can be visualized and entered.

Once the peritoneum is open, a 12-mm trocar can be inserted under direct visualization, and the peritoneal cavity is insufflated with carbon dioxide. The authors perform most LCs with a 5-mm, 30°-angled laparoscope. However, in patients who are significantly obese, a 10-mm trocar should be used to perform the cystic duct dissection, as the small 5-mm laparoscope does not generate enough light inside the large abdominal cavity of an obese patient and may compromise the surgeon’s ability to clearly visualize all vital structures surrounding the cystic duct.

Considering that most complications related to laparoscopic gallbladder surgery occur during the dissection and exposure of the cystic duct, one should never work under poor light and inadequate visualization at that point in the operation. Beginning the procedure with the 10-mm laparoscope in place via the 12-mm trocar is fairly easy, as is changing to a 5-mm laparoscope once the dissection and exposure of the cystic duct and artery are completed.

Second, subsequent trocar placement in children must be determined individually once the gallbladder fundus is visualized with the laparoscope. A 5-mm trocar is typically placed in the subxiphoid region. Another 5-mm trocar should be placed in the mid-right upper quadrant of the abdomen (at the level of the midclavicular line) in a way that allows the introduction of a laparoscopic instrument used to manipulate the neck of the gallbladder. This trocar is usually placed about 2 cm below the costal margin. However, in small children, it must be placed closer to the costal margin.

The last trocar should be a 5-mm trocar placed laterally in the right upper quadrant. This trocar is used for placement of a grasping instrument, such as a McKernan grasping-locking forceps, that is placed on the fundus of the gallbladder for retraction. For that reason, the trocar should not be placed too far from the costal margin. (See the image below.)

Diagram illustrating the technique for laparoscopi Diagram illustrating the technique for laparoscopic cholecystectomy. The gallbladder is retracted with grasping 5-mm laparoscopic instruments, and clips are applied over the cystic duct and artery.

Once the gallbladder fundus is grasped, it must be displaced towards the patient’s right shoulder, above the right lobe of the liver. This maneuver allows for exposure of the neck of the gallbladder. One assistant should keep the fundus of the gallbladder pushed toward the patient’s shoulder region at all times. This elevates the neck of the gallbladder together with the cystic duct and artery, facilitating dissection and exposure.

The third important step is the exposure and dissection of the neck of the gallbladder. If significant inflammatory changes are identified, the authors prefer to perform an intraoperative cholangiography to help define the anatomy of the cystic duct and its relationship to the gallbladder and common bile duct.

Other indications for intraoperative cholangiography are a history of jaundice, pancreatitis, dilation of the common bile duct, and the presence of small gallstones. The benefits of using cholangiography have not been proven for routine cholecystectomy, routine screening for congenital anomalies, or assessment of the common bile duct for obstruction in the absence of clinical suspicion.

Cholangiography can be performed intravenously or percutaneously. The authors prefer to perform a cholangiography through the gallbladder. This can be easily performed by placing a percutaneous catheter in the gallbladder under laparoscopic visualization. The gallbladder is filled with water-soluble dye, and radiographic images are obtained with live fluoroscopy.

Intraoperative cholangiography allows the surgeon to identify any points of biliary obstruction and determine whether any evidence of common bile duct stones is present. In addition, it provides information about the length and relative location of the cystic duct, facilitating dissection and minimizing the risk of injury to the ducts.

The dissection for exposure of the cystic duct and artery is started at the neck of the gallbladder. Initially mobilizing the visceral peritoneum and any inflammatory adhesions away from the neck of the gallbladder is important. This can be easily performed using a hook with electrocautery. The authors usually have the surgeon manipulate the laparoscopic camera, with a hook or Maryland dissector in the right hand placed via the subxiphoid trocar.

The assistant should be retracting the fundus of the gallbladder toward the right shoulder at all times and should also have a blunt grasper in the right hand to manipulate the neck of the gallbladder. This manipulation involves moving the neck back and forth, toward the patient’s right and left side, providing dynamic exposure for the surgeon. The assistant should never keep the neck of the gallbladder in a fixed and locked position.

Using careful dissection, the surgeon must achieve the so-called "critical view." This refers to the visualization of the cystic duct and artery as they enter the gallbladder.

Dissecting towards the common bile duct and exposing the duct is not necessary. Once the point of entry of the cystic duct is clearly visualized on the gallbladder, the duct can be clipped and divided. The authors prefer to place one 5-mm clip on the cystic duct next to the gallbladder and 2 clips towards the common bile duct.

Again, the dissection and exposure of the cystic duct is kept very close to the gallbladder, which should minimize the risk of injury to the common bile duct. The cystic artery can be simultaneously clipped with the cystic duct or can be separately clipped, depending on its proximity to the duct.

Completely dissecting the artery and fully exposing it is not necessary, because this may lead to bleeding from small branches. In young children, cauterizing the artery is possible. Controlling the artery with a LigaSure or Harmonic scalpel is also possible. However, such devices are rarely necessary during LC.

Once the cystic duct is divided with laparoscopic scissors, its lumen should be inspected to make sure that no evidence of any abnormalities suggests the presence of an injury to the common bile duct. At this point in the operation, the surgeon should use an electrocautery hook to divide the visceral peritoneum at the plane between the gallbladder and the liver. Again, the assistant moves the gallbladder back and forth, providing continuous exposure of that plane until the gallbladder is completely free.

If a hole is accidentally made in the gallbladder wall, the leakage of bile and gallstones can be controlled by placing the grasping instrument over the hole. Any stones that leaked should be removed using a suction irrigation device.

Occasionally, a gallbladder is partially intrahepatic. In such cases, removing a wedge of liver tissue with the gallbladder is necessary. Electrocautery dissection at high settings should provide sufficient hemostasis. Once the gallbladder is completely disconnected from the liver, the authors move the laparoscope to the subxiphoid port and insert a 10-mm endopouch through the umbilical port. The gallbladder is placed inside the bag and brought into the trocar.

In most cases, the gallbladder is too big to be removed through the 12-mm port. The authors prefer to enlarge the umbilical incision and expose the muscle fascia, which is then divided with electrocautery. This allows extraction of the pouch that contains the gallbladder. The fascia can then be reapproximated with Vicryl sutures.

After the gallbladder is removed, the authors prefer to reinspect the liver bed to make sure that no evidence of bleeding or bile leaking is present. Any residual bile is suctioned. At this point, all trocars are removed under direct laparoscopic visualization, and the operation is completed. The fascia at the 5-mm trocar sites does not need to be closed, unless the patient is younger than 5 years.

Mini-laparoscopic Technique

Experience has demonstrated the feasibility of a mini-laparoscopic technique for removal of the gallbladder in pediatric patients. The laparoscopic operation can be achieved using 3-mm instruments and minimal use of ports. A 3-port mini-approach has been reported.

However, patient selection is essential when performing this operation with mini-instruments. One should not sacrifice good visualization and optimal exposure of the vital structures. The risk of iatrogenic injury to the common bile duct outweighs any benefit that can be achieved with mini-scopes and mini-instruments. Inflammation and adhesions, frequently seen in symptomatic patients, may limit the use of the mini-laparoscopic approach.

Complications of Cholecystectomy

LC is associated with some risks. Major complications include bleeding, pancreatitis, leakage from the duct stump, and major bile duct injury. The risk of ductal injury increases from 0.1-0.2% in OC to 0.5-1% in LC.

However, Holcomb et al reported no iatrogenic injuries with LC in their first 100 patients.[23] They stated that with conscientious surgical care, morbidity related to the laparoscopic approach can be minimized.

Other procedures used in conjunction with cholecystitis also carry risks. Choledochotomy and endoscopic papillotomy may be performed independently or in conjunction with cholecystectomy to aid in the treatment of choledocholithiasis. The overall mortality rate from choledochotomy (also applied to papillotomy) was determined to be 2.1%; however, by excluding patients with preexisting cholangitis or pancreatitis, the mortality rate decreased to 1.2% and the morbidity rate was 6-8%. The most serious complications resulting from these procedures have been hemorrhage, cholangitis, and pancreatitis.

In general, the complication rates of cholecystitis and cholecystectomy are low in the absence of critical illness. The ability to tolerate general anesthesia and operative conditions for cholecystectomy has become the most significant indicator of outcome in cholecystitis. As a rule, children recover well once appropriate operative treatment has been established.

Percutaneous Transhepatic Cholecystostomy

One alternative to cholecystectomy is percutaneous transhepatic cholecystostomy. In this approach, a catheter is threaded directly into the gallbladder and placed to allow gravity drainage.

Cholecystostomy is especially useful in acalculous cholecystitis and in seriously ill patients with simple gallstones in whom obstruction of the common bile duct is ruled out. Because cholecystectomy is the standard of care for cholecystitis, cholecystostomy is usually reserved for seriously ill patients who may not tolerate surgery.

Diet

Dietary recommendations in gallbladder disease differ according to the stage of disease. The two available strategies include acute management and preventive measures. The patient with acute cholecystitis should ingest nothing by mouth (NPO) and undergo nasogastric evacuation of gastric contents. The goal in this stage of disease is to eliminate unnecessary stimulation to the biliary system and to reduce infectious exposure. Additionally, preparations can be more readily made for surgery.

No widely accepted dietary therapy exists for the prevention of cholecystitis; however, the contemporary Western diet and obesity have been implicated as predisposing factors in the development of gallstone disease. Certainly, diet and exercise are influential, and the West is infamous for poor dietary and exercise habits.

Results from a Jamaican cohort study by Walker et al indicated a link between diet and cholecystitis. The authors examined a population of patients with sickle cell disease similar to that examined by Winter et al in the United States. The progression of biliary sludge to cholecystitis and the need for cholecystectomy was significantly decreased in the Jamaican population. Walker et al theorized that dietary differences in the two countries were causal. These cultural influences affect the adolescent and adult populations.[24]

Presumably, a decrease in cholesterol and fatty food consumption would lower the risk of cholecystitis, but no specific data supporting this have been collected. Dietary restriction to achieve weight reduction may minimize risk in children with obesity. Weight loss should be controlled and gradual, because rapid reduction may increase bile cholesterol saturation and gallbladder stasis, actually promoting stone formation.

Dietary management of chronic gallbladder disease in the absence of surgery also follows this preventive approach, with the added goal of preventing symptoms. Although biliary colic in children is less likely to directly correspond to fatty food consumption than it is in adults, the patient should still be advised to avoid high-fat meals.

Finally, in patients with hyperalimentation-associated gallstones, administer low-dose enteral feedings, which may prevent stone formation by stimulating contraction of the gallbladder and reduction of bile stasis.

Activity

Cholecystitis does not directly affect activity. Children should remain as active as their condition, comfort, and development allow. Postoperatively, activity recommendations correspond with the general precautions recommended abdominal surgery. Ambulation, as soon as tolerable, improves outcomes, although patients should restrict lifting to less than 5 pounds for several weeks.

Transfer Criteria

Treat the pediatric patient with cholecystitis at a facility with the services of a pediatrician and a staff proficient in the care of children. A pediatric surgeon should be available, preferably one proficient at LC. In addition, appropriate radiologic and gastroenterologic procedures (eg, cholangiography, ERCP) should be readily available.

If these resources are deficient, consider transfer to an appropriate institution. Outcomes for children with cholecystitis who are given proper care are generally excellent, although complications can occur; the prognosis plummets with neglect. Clinicians caring for these children should be experienced in treating gallbladder disease and have all necessary resources at their disposal.

Prevention of Cholecystitis

The focus of prevention of cholecystitis is the minimization of controllable risk factors. Because most of these factors for pediatric cholecystitis are related to underlying disease processes, options are limited, but conscientious treatment by the primary provider, knowledge of risks, and close observation for symptoms are helpful.

Reduction of Risk Factors

As previously mentioned, weight control in the child with obesity may decrease the risk of cholelithiasis and many other long-term sequelae.

The use of pancreatic enzymes and bile acid supplements in patients with CF decreases the saturation and lithogenicity of bile.

Limited enteral feedings in children who require long-term hyperalimentation decrease the biliary hypofunction observed in prolonged fasting

The addition of ursodeoxycholic acid (Actigall) in settings of chronic biliary stasis may mitigate the potential for cholelithiasis to develop

Seriously consider the risks associated with medications, (eg, oral contraception, furosemide, ceftriaxone, octreotide, cyclosporine) before using them in patients who are at risk

Consultations

Use a team approach to achieve proper care of the patient with cholecystitis. Consult a pediatric gastroenterologist and surgeon early in the treatment of the patient. The assistance of a dietitian may be very useful if observation without surgery is to be used. In addition, consulting a radiologist is helpful if percutaneous cholecystotomy is considered.

Long-Term Monitoring

The surgeon should follow up with the patient 2 weeks after surgery to monitor wound healing and to ensure no postoperative complications are present. The clinician should be sensitive to any indication of biliary injury or obstruction and investigate any such signs quickly. The patient should be aware that common bile duct stones may still occur in the absence of the gallbladder.

Evaluate future abdominal pain in the right upper quadrant, because it may represent residual or recurrent common bile duct stones. If unrecognized, bile duct stones may lead to biliary obstruction and hepatocyte damage.

 

Medication

Medication Summary

Surgical intervention is the definitive treatment for cholecystitis, especially in the pediatric population. However, bile acids have been used with some success for the dissolution of cholesterol gallstones.

Gallstone Solubilizing Agents

Class Summary

Gallstone solubilizing agents are used for the medical dissolution of cholesterol gallstones. Ursodiol and chenodiol are orphan drugs that have been approved by the FDA for gallstone dissolution; however, these agents have not been FDA approved yet for children.

Ursodiol (Actigall, Urso)

Ursodiol suppresses hepatic synthesis and secretion and intestinal absorption of cholesterol. It does not seem to significantly inhibit synthesis and secretion of endogenous bile acids or affect secretion of phospholipids into bile.

Overall, ursodiol increases the concentration at which cholesterol saturation occurs and allows cholesterol to solubilize in an aqueous medium. It is preferred over chenodiol because of its relative safety.

Chenodiol (Chenix)

Chenodiol acts in a similar fashion to ursodiol; however, its metabolite lithocholic acid is hepatotoxic and may cause hepatobiliary damage itself. Chenodiol given at low doses (< 10 mg/kg/d) may actually increase the rate of cholecystectomy. Because of these effects, ursodiol is preferred.

Antibiotics

Class Summary

Antibiotics with biliary excretion covering enteric pathogens may be administered to control infection. The combination of ampicillin, gentamicin, and clindamycin has been a common and well-accepted regimen. More recently, additional antimicrobial agents, including piperacillin-tazobactam and second-generation and third-generation cephalosporins, have been recommended when antibiotic treatment is indicated. The choice of agent depends, importantly, on whether the presumptive bacterial infection is acquired in the community or the healthcare facility.

The use of antibiotics remains controversial, and much of the available data regarding antimicrobial usage derive from studies in adults. These reports generally agree that antibiotics are not necessary in simple cases and should be reserved for persistent fever or worsening of the condition.

Ampicillin

Ampicillin is a broad-spectrum penicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms.

Gentamicin

Gentamicin is an aminoglycoside antibiotic for gram-negative bacteria, including Pseudomonas species. It is synergistic with beta-lactamase against enterococci. It interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.

Clindamycin (Cleocin)

Clindamycin is a semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of parent compound lincomycin. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It distributes widely in the body, without penetration of the CNS. It is protein bound and excreted by the liver and kidneys. It is effective against gram-positive aerobic and anaerobic bacteria (except enterococci).

Antibiotic

Piperacillin/tazobactam (Zosyn)

Piperacillin-tazobactam is a combination antimicrobial drug comprising the penicillin analogue piperacillin and the β-lactamase inhibitor tazobactam. This combination has activity against a broad spectrum both of Gram-positive and Gram-negative organisms as well as Pseudomonas aeruginosa.