Richard K Gilroy, MBBS, FRACP,
Associate Professor, Medical Director of
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Associate Professor, Department of Internal
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Alex J Mechaber, MD, FACP,
Associate Dean for Undergraduate Medical
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Clinical Professor, School of Pharmacy,
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Biliary colic is a symptom of discomfort and is often not accompanied by any clinical signs. It represents one of the causes of epigastric pain. It is the most common presentation of symptomic gallstone disease (cholelithiasis/choledocholithiasis). Because this is a symptom, numerous other disease processes may result in pain that is similar to biliary colic, and, certainly, biliary colic is not the most common cause of epigastric pain. For this reason, other disease processes should be considered during the evaluation of patients being considered to have biliary colic. (See image belows and Images 1, 3.)
Mechanism of biliary colic.
Careful history and examination are cornerstones to making an accurate clinical diagnosis, essentially because of the high incidence of gallstones in the population and because most gallstones are asymptomatic. The potential disastrous implications of a misdiagnosis as biliary colic instead of alternative diagnoses that may present with epigastric pain (eg, atypical myocardial ischemia) cannot be overemphasized. Patients also can be particularly unhappy and frustrated when their pain is not resolved following cholecystectomy. The differential diagnosis section lists other important medical conditions one should consider in patients who present with possible biliary colic (see Differentials).
History should elicit the nature, intensity, location, duration, onset, cessation, associated factors, aggravating factors, relieving factors, radiation, and frequency (NILDOCARRF) of the pain (see History). The pain of biliary colic is listed inaccurately as a colic. This term implies a paroxysmal pain that waxes and wanes, when, in actuality, the pain of biliary colic is generally a constant and slowly progressive pain. The pain generally follows a meal and may wake up a person several hours later. In fact, pain immediately with a meal is not characteristic of biliary colic.
It is important while taking the history that one evaluates the risk factors for stone formation, addresses and excludes other potential causes for the pain, and concurrently evaluates medical comorbidities that may influence management (eg, cardiovascular disease).
This visceral pain is believed to result from impaction of a gallstone in the cystic duct and/or ampulla of Vater. The resulting impaction causes distension of the gallbladder and/or biliary tract, and this distension activates visceral afferent sensory neurons. The resultant pain is commonly localized poorly and generally refers midline to the representative dermatomes T8/9 (mid epigastrium, right upper quadrant), although it may radiate to the right upper quadrant. Localized pain or persistent pain generally represents a complication of cholelithiasis or choledocholithiasis (eg, cholecystitis, cholangitis, pancreatitis).
Biliary colic is the presenting symptom in 80% of patients with gallstone disease who seek medical care; however, only 10-20% of all individuals with gallstones experience severe gallstone pain. The risk of developing biliary pain or stone-related complications in asymptomatic patients is low, at 1-2% per year. For this reason, clinical practice favors treatment of only symptomatic disease, with the exception of a few unique circumstances. Two thirds of patients presenting with their first attack of biliary colic have recurrent pain within 2 years.
Nonpain symptoms that may be associated with biliary colic are inconsistently relieved with cholecystectomy (approximately 44%) and are more likely relieved in the presence of gallstones than in acalculous disease.
Fatty food intolerance (fatty dyspepsia) is not a symptom of biliary colic.
A gallstone produces visceral pain by obstructing the cystic duct or ampulla of Vater, resulting in distention of the gallbladder or biliary tree. Pain is relieved when the gallstone migrates back into the gallbladder, passes through the ampulla, or falls back into the common bile duct (CBD). The pain of biliary colic may accompany sphincter of Oddi spasm. (See image below and Image 2.)
Asymptomatic individuals with gallstones develop pain at an annual rate of 1-4%, with approximately 10% of individuals developing symptoms in 10 years and 20% developing symptoms in 20 years.
Limited international data appear to support a similar incidence of biliary colic in all populations with gallstones. The incidence of gallstones is greater in some races and cultures than in others.
By definition, uncomplicated gallstone disease is not associated with signs or symptoms of systemic disease, such as fever, jaundice, or leukocytosis. Patients with uncomplicated gallstone disease experience self-limited pain. Presentation is associated with only limited morbidity and never mortality, despite some patients' perception of the severity of pain and its significance. The frequency of progression to acute cholecystitis is 10-30%. Ibuprofen use may decrease the likelihood of progression.
In the United States, the prevalence of gallstone disease is highest among Hispanic Americans and Native Americans, especially the Pima Indians of Arizona, with 75% of women developing cholesterol gallstones by early adulthood.
Biliary colic is more common in women than in men, primarily related to the 2- to 3-fold increased incidence of cholelithiasis in women.
The incidence of biliary colic depends on the incidence of gallstones. For this reason, the condition is rare in patients younger than 20 years and increases with age, occurring in approximately 2-4% of men older than 60 years and approximately 3-8% of age-matched women.
Note that, in general, there is no clear association between the presence of gallstones and upper abdominal pain.
Biliary colic usually starts abruptly and reaches maximum intensity within 60 minutes in two thirds of patients.
The pain generally continues without fluctuation and resolves gradually over 2-6 hours. Pain lasting longer than 6 hours should raise the suspicion for acute cholecystitis.
NILDOCARRF (an acronomy for the following)
Nature: Many persons with this condition have difficulty describing the nature of the pain. It is a vague aching/cramping discomfort and generally is not sharp. The pain is constant rather than colicky; however, some interindividual variability exists.
Intensity: Among individuals, intensity is quite variable; however, the pain may be severe. Prolonged severe pain should raise concern that another etiology may be present.
Location: The epigastrium is the most common site, followed by the right upper quadrant; however, it may be located in many different sites within the abdomen. The pain tends to recur at the same sites. Infrequently (7%), pain may be represented in a retrosternal location.
Duration: The pain lasts from 30 minutes to 6 hours.
Onset: Progressive in onset, it reaches peak intensity within 30-60 minutes.
Cessation: Gradual persistent pain increases the likelihood of another etiology for the pain, including other complications of gallstones.
Associated factors: This condition may be associated with nausea, vomiting, or diaphoresis. Patients often cannot get comfortable. Patients generally do not have a fever.
Aggravating factors: Pain often follows a few hours after meals and may occur at night and wake the patient from sleep. Pain traditionally does not occur with meals or very soon after. Morphine has been noted to increase the pain in some people with biliary colic secondary to sphincter of Oddi dysfunction (SOD).
Relieving factors: Narcotic analgesia, nonsteroidal anti-inflammatory drugs (NSAIDs), and nitrates help relieve the pain.
Radiation: Pain may radiate to the right upper quadrant and to the back, following the subcostal margin. Other less common sites include retrosternal areas and the left upper quadrant. Isolated left arm (cardiac) and sharp right shoulder tip pain (cholangitis) should prompt consideration of alternative diagnoses.
Frequency: If the patient has had a previous attack, the likelihood of recurrence is higher. Fatty meals inconsistently elicit the pain, and nocturnal occurrence of pain is not infrequent. Repeat bouts in the same day may herald other complications.
Uncomplicated biliary colic leaves no persisting symptoms following the acute attack.
Finally, in relation to the patient with acalculous disease with a question of biliary pain, the ROME II diagnostic criteria were published to help evaluate the patient considered to have gallbladder dysmotility. These criteria are listed below. Note that all criteria are pain related.
Episodes of severe steady pain located in the epigastrium and right upper quadrant
All of the following:
Symptom episodes last 30 minutes or more, with pain-free intervals.
Symptoms have occurred on 1 or more occasions in the previous 12 months.
The pain is steady and interrupts daily activities or requires consultation with a physician.
There is no evidence of structural abnormalities to explain the symptoms.
There is abnormal gallbladder functioning with regard to emptying.
Initial inspection often reveals an individual who is diaphoretic, pale, rolling about, and unable to get comfortable. Vomiting may accompany the pain.
Examination may reveal some of the physical features associated with gallstone formation (eg, overweight, middle-aged, female).
Occasionally, features of other conditions associated with an increased incidence of gallstones may be observed. This may extend to observing an individual with jaundice with stigmata of chronic liver disease. More often than not, physical findings are more important for excluding other causes for the pain.
Patients with uncomplicated biliary colic do not have fever, chills, hypotension, or other signs of a significant systemic process.
Sinus tachycardia is common during pain.
Much interindividual variability exists when the pain is described; generally, it is at the milder end of the spectrum, although the pain may be excruciating for some individuals.
Rebound, guarding, absent bowel sounds, or a palpable mass support an alternate diagnosis.
The risk factors for cholelithiasis have been outlined in the eMedicine article Cholelithiasis.
A postulate explaining the greater nocturnal occurrence of biliary colic pain concerns the biliary anatomy. The horizontal lie of the gallbladder upon recumbency (sleeping) is believed to predispose patients to stone migration and subsequent impaction.
Biliary dyskinesia and SOD present with a pain that often is consistent with biliary colic. These individuals often have undergone cholecystectomy without resolution of symptoms.
Recurrent pain occurs in as many as 20% of people who have undergone cholecystectomy and is most common in those who have undergone cholecystectomy for acalculous disease or for atypical symptoms.
Before allocating someone to the category of biliary dyskinesia/SOD, considering other causes of the symptoms described, particularly those outside the biliary system, is important. Investigations should focus on excluding retained stones in the biliary system. Treatment of SOD should take place at select institutions with extensive experience in this area. The investigation and treatment of this condition are beyond the scope of this article; however, a brief summary follows:
SOD is uncommon and accounts for 10% of people with postcholecystectomy abdominal pain in one series. It is a difficult diagnosis to establish and involves a combination of careful history, possibly some supportive laboratory tests, and cholangiography to exclude choledocholithiasis. Often, sphincter of Oddi manometry is performed.
Those most likely to respond to treatment by endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy are those with a history of classic biliary pain, abnormal liver enzymes in association with the pain, and delayed drainage post-ERCP.
Relief of pain after stenting the sphincter also is predictive of response to sphincterotomy.
Some trials have shown support for the use of nifedipine and nitrates in selected populations.
CBC count results are normal in uncomplicated biliary colic; an abnormality suggests complicated biliary disease (eg, cholecystitis).
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, and amylase assay results are normal in uncomplicated biliary colic; an abnormality suggests a complication (eg, cholecystitis, cholangitis, pancreatitis).
If clinical suspicion warrants more extensive investigation into alternate diagnoses, consider creatine kinase and cardiac enzymes evaluation or other investigations accordingly. Minor increases in alkaline phosphatase accompanied by rises in bilirubin may be seen with choledocholithiasis. Increases in AST and ALT accompanied by right upper quadrant pain often herald the development of cholangitis.
Abdominal ultrasonography (US) is the diagnostic method of choice to confirm gallstones. US is sensitive (95%), and its specificity is guided by pretest probability. (See image below and Image 4.)
The picture of a classic history for biliary colic and gallstones within the gallbladder with some wall edema increases specificity. An atypical history with a single large stone makes this specificity lower, with overall estimates of specificity approximately 60%.
The test is safe and relatively inexpensive. Negative US findings exclude biliary colic in most instances. Visualizing cystic duct obstruction, the most common cause of biliary colic, is uncommon. Biliary tract dilation also is not observed often.
Oral cholecystography (55-85%), although at times sensitive (ie, when the gallbladder is able to be filled with contrast, sensitivity is 90%) for the evaluation of gallstones, has been replaced by US.
It may have advantages over US for assessing cystic duct patency and gallbladder function, but this indication is infrequent and is reserved for those with symptomatic gallstones who are elderly and not operative candidates.
Dissolution therapy may be contemplated but rarely is it indicated.
Hepatobiliary (hepatoiminodiacetic acid) scintigraphy, or HIDA, may have a role in evaluating acute cholecystitis. It has a role when classic symptoms of biliary colic occur and imaging studies fail to demonstrate stones. (See images below and Images 5-7.)
Generally, either cholecystokinin (CCK) or morphine is added to improve the sensitivity of the test, although much controversy surrounds the sensitivity and specificity of the addition of morphine to the procedure.
Ejection fractions of less than 50% have been found with those more likely to respond to cholecystectomy; however, some authorities suggest values of less than 35%. Lower ejection fractions provide increased specificity at the expense of sensitivity.
In the context of typical symptoms of biliary colic and an ejection fraction of 20%, these authors usually would recommend cholecystectomy.
HIDA (or gallbladder) scan.
HIDA (or gallbladder) scan.
HIDA (or gallbladder) scan.
ERCP has a role in patients with persisting symptoms consistent with biliary colic that have failed to resolve with cholecystectomy. The aim is to primarily exclude choledocholithiasis.
When used with biliary manometry, ERCP is useful for predicting which patients are more likely to respond to sphincterotomy, in particular those classified as type II SOD.
ERCP has a therapeutic role in type I and type II SOD. It is the means by which a sphincterotomy may be performed to treat this condition.
Some authors use this procedure to aspirate bile, looking for crystals. Using the results of this procedure for predicting those who will respond to cholecystectomy has not been validated at this point.
Abdominal x-ray has a very low sensitivity and specificity in the diagnosis of biliary colic. The role is to exclude other pathology (eg, bowel obstruction, perforation).
Magnetic resonance cholangiopancreatography has the same role as ERCP in biliary disease. It offers no advantage over US but may have a role when one is looking for a retained common duct stone.
Patients who have had gallstones removed at ERCP (ie, those who have had a sphincterotomy), who have negative findings for cholelithiasis on US, and who are candidates for surgery should be offered cholecystectomy.
High-risk candidates referred for elective cholecystectomy should be considered on a case-by-case basis.
Patients with cholelithiasis and choledocholithiasis who are operative candidates should be offered laparoscopic cholecystectomy and CBD exploration, acknowledging a 5% chance of conversion to an open procedure.
Surgery is recommended for symptomatic gallstone disease, and all symptomatic individuals should be considered for laparoscopic cholecystectomy when appropriate.[2, 3]
Patients at higher-than-normal operative risk must be considered individually. Cost and risk-benefit analysis does not support prophylactic cholecystectomy in asymptomatic individuals; however, it does support surgical intervention in symptomatic individuals. This is discussed in the eMedicine article Cholelithiasis.
Supportive measures are indicated for patients with uncomplicated biliary colic, with symptoms usually resolving within 2-3 hours. Continuous or recurrent symptoms despite analgesia likely herald a complication of gallstone disease, most commonly acute cholecystitis.
Most authors favor narcotic analgesics over other agents for the immediate relief of pain. Meperidine (pethidine) at 1-1.5 mg/kg intramuscular injection (not to exceed 100 mg) every 3 hours is preferred. In view of the theoretical association with increased biliary motility and spasm, morphine generally is avoided.
Several controlled trials of diclofenac, tenoxicam, and ketorolac seem to have demonstrated therapeutic benefits in both pain relief and decreased likelihood of progression to acute cholecystitis. An increase in adverse effects in patients who are dehydrated or elderly should be considered. In the setting of nausea and vomiting, a parenteral route is favored.
Antispasmodics (eg, papaverine, atropine) and nitrates have a very limited, if any, role in the treatment of biliary colic.
Nausea: Use metoclopramide or prochlorperazine intravenously.
No acute surgical intervention is warranted because uncomplicated biliary colic resolves with conservative treatment.
Several studies have reviewed the treatment of symptoms believed to be related to gallstones.
Patients who undergo elective cholecystectomy for biliary colic have shorter lengths of stay in the hospital and less complicated operative courses than those presenting with complications of gallstone disease. Relief of symptoms occurs in approximately 85% of individuals. The procedures performed were, on the average, shorter and with shorter periods of convalescence. Many authors favor elective surgery for patients with biliary colic.
Patients with atypical (ie, nonpain) symptoms show inconsistent relief of these symptoms (eg, fatty food intolerance, flatulent dyspepsia). Laparoscopic therapy is favored.
In patients with symptoms of biliary colic without gallstones, the treatment options become more difficult. A combination of a positive biliary scintigraphy with CCK (ejection fraction < 50%) and classic symptoms appears to respond the best to cholecystectomy. In general, patients with symptoms typical of biliary colic, with normal US findings, positive scintigraphy findings, and no evidence of acid-peptic disease, have the greatest benefit from laparoscopic cholecystectomy. Patients with symptoms that persist after cholecystectomy warrant evaluation in specialized facilities that focus on biliary motility disorders.
Nonsurgical treatment is selected for high-risk surgical candidates.
Early surgical consultation is appropriate if symptoms do not resolve in the expected time frame. Persistent symptoms suggest the possibility of acute cholecystitis. In those in whom a diagnosis is established and symptoms resolve, elective consultation is appropriate.
During the acute attack, patients typically are anorectic. After resolution of the attack, some authors favor avoidance of high-fat meals. Controlled data are lacking to support this approach, and a liberal healthy diet is not unreasonable. A diet to prepare an individual for surgery is advised (eg, weight reduction in patients who are obese).
Pain control is essential to quality patient care. NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. They are used for mild to moderate pain. Their mechanism of action is unknown, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist (eg, inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, various cell membrane functions). Opioid analgesics act at the CNS mu receptors. They are inexpensive and have proven effective.
Analgesic with multiple actions similar to those of morphine; may produce less constipation, smooth-muscle spasm, and depression of cough reflex than equal analgesic doses of morphine.
Potent semisynthetic opiate agonist similar in structure to morphine. Approximately 7- to 8-times as potent as morphine on mg-to-mg basis, with shorter or similar duration of action (ie, 4-5 h).
The CNS vomiting center (VC) may be stimulated directly by GI irritation. Increased activity of central neurotransmitters, dopamine in the chemoreceptor trigger zone, or acetylcholine in the VC appears to be a major mediator for inducing vomiting. Antidopaminergic agents (eg, metoclopramide, phenothiazines) are effective for nausea due to GI irritation.
Dopamine antagonist that stimulates acetylcholine release in the myenteric plexus. Acts centrally on chemoreceptor triggers in the floor of the fourth ventricle, which provides important antiemetic activity.
Patients with biliary colic should be referred for elective cholecystectomy, particularly if symptoms are recurrent.
Even high-risk surgical candidates should be considered for laparoscopic cholecystectomy. Good results can be achieved in these patients, and data appear to support this over ERCP. Patients who have had an ERCP remain at risk for biliary complications of gallstone disease. Good data now support laparoscopic cholecystectomy with laparoscopic CBD exploration when undertaken by experienced people rather than ERCP prior to cholecystectomy.
In the rare instance in which a patient has had CBD clearance with ERCP and has no residual stones on imaging study, these authors favor cholecystectomy. No randomized data are available to support this; however, "once a stone former, always a stone former … until cholecystectomy."
Byrne et al examined the outcomes of more than 130 patients who had CBD stones removed at ERCP, 59 of whom subsequently underwent elective cholecystectomy, 27 of whom planned to have cholecystectomy, and 47 of whom were managed with a "wait-and-see" approach. All patients in the study had an intact gallbladder at the time of ERCP. The authors found that 9 patients in the wait-and-see group (8 of whom were poor surgical candidates) developed complications, including recurrent pain and/or abnormal liver function tests, recurrent biliary colic, and pancreatitis. Byrne et al concluded that in patients with choledocholithiasis who do not undergo elective cholecystectomy, particularly those in whom there is a high operative risk, recurrent biliary complications are relatively common.
Cholecystectomy generally cures the pain of biliary colic and is the treatment of choice for this condition. Avoidance of fatty meals does not reduce symptoms of biliary colic, nor does it result in less frequent attacks.
Biliary colic lasting longer than 6 hours, fever, and right upper quadrant tenderness may indicate acute cholecystitis; the addition of jaundice to the above symptoms and signs implies cholangitis.
After the initial presentation, 30% of patients have no further attacks and the approximate frequency of recurrent symptoms after an initial attack is 30% in the 2 years following. Serious complications following an initial attack of biliary colic are uncommon, with a frequency of approximately 1% per year. One study favors routine cholecystectomy for those with symptoms consistent with biliary colic. This is based on reduced overall cost, decreased number of hospitalizations, reduced emergency department visits, and, importantly, diminished likelihood of conversion from a laparoscopic to open procedure and the complications from this surgery.
Recurrent biliary colic occurs in 50-75% of patients after the initial episode. Most patients who develop complications, such as cholecystitis, experience biliary colic prior to the complications. A cost analysis appears to support referral of those with symptoms of biliary colic for cholecystectomy. Of greatest importance is the fact that biliary colic is the most sensitive and specific symptom of symptomatic cholelithiasis, and one should be aware that other symptoms (eg, bloating) have low specificity for symptomatic gallstone disease.
Cholecystectomy cures symptoms of biliary colic in approximately 80-85% of patients with gallstones on ultrasound findings. Nonpain symptoms related to cholelithiasis are relieved inconsistently (approximately 40%) by cholecystectomy.
Postcholecystectomy syndrome encompasses an array of clinical symptoms that persist following cholecystectomy. They may be of biliary or nonbiliary origin. More often, these are symptoms like bloating, excessive flatulence, and fatty-food intolerance. In any event, if the primary indications for cholecystectomy are these atypical symptoms, it is imperative that during informed consent a patient is made aware that these are not improved consistently following cholecystectomy. Every good operation has its indications and limitations. To discuss and document these for every individual patient is important.
Disorders that warrant exclusion, in the event that pain persists following cholecystectomy, include those of both biliary and nonbiliary origins. Retained stones in the CBD (ie, choledocholithiasis) should have been excluded with an operative cholangiogram, and this is a good place to start with the workup of persisting symptoms. Clinical data that would support choledocholithiasis include any feature of cholangitis, clinical stigmata of obstruction, and laboratory tests (ie, increased bilirubin or liver enzymes following attacks).
Nonbiliary causes include gastrointestinal disorders (eg, reflux esophagitis, peptic ulcer disease), nongastrointestinal disorders (eg, atypical angina), and, importantly, functional disorders, such as irritable bowel syndrome (IBS). Another word of caution is that 2 common conditions may coexist (ie, gallstones and IBS). To reiterate, a careful history is the cornerstone of establishing a provisional diagnosis of biliary colic in an individual (commonly a middle-aged female) who may present with IBS and gallstones on US findings.
The difficult patient is one for whom data on the most appropriate therapy is not available. This is the high-risk surgical patient with biliary colic. A good study that endeavors to address this is that by Targarona et al, which favors laparoscopic cholecystectomy over ERCP with sphincterotomy for choledocholithiasis.
Carr-Locke's group showed that, even with sphincterotomy, the risk of recurrent biliary tract related symptoms or complications was significant (approximately 20%).
The ongoing challenges in biliary tract disease are outside the scope of this article; however, a good review article on this subject is that by Stiegmann.