Biliary Colic

Background: 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.

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.

History should elicit the nature, intensity, location, duration, onset, cessation, associated factors, aggravating factors, relieving factors, radiation, and frequency (NILDOCARRF) of the pain. 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 general 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.

Pathophysiology: 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.

Frequency:

• In the US: 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.

• Internationally: 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.

Mortality/Morbidity: 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 possibly may decrease the likelihood of progression.

Race: 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.

Sex: Biliary colic is more common in women than in men, primarily related to the 2- to 3-fold increased incidence of cholelithiasis in women.

Age: 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.

Treatment
Medical Care: 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.

• Pain

• 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.

Surgical Care: 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 scintography with CCK (an ejection fraction <50%)>

• Nonsurgical treatment is selected for high-risk surgical candidates.

Consultations: 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.

Diet: 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).

Activity: Bed rest usually is recommended until the pain resolves; patients may resume full activity thereafter.

Medication
NSAIDs and/or opiate agonists are used to provide pain relief. Nausea is treated with antiemetics and intravenous fluids for consequent dehydration.
Drug Category: Analgesic agents -- 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.

Drug Name	Meperidine (Demerol) -- 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.
Adult Dose	50-150 mg PO/IV/IM/SC q3-4h prn
Pediatric Dose	Not established; problem rare <20>
Contraindications	Documented hypersensitivity; within 2 wk of MAOIs; upper airway obstruction or significant respiratory depression; intracranial lesions; multiple doses in patients with renal failure; predisposition to seizures; during labor when delivery of premature infant is anticipated
Interactions	Increased respiratory and CNS depression with coadministration of cimetidine; hydantoins may decrease effects; protease inhibitors (eg, ritonavir) may increase normeperidine levels, enhancing risk of CNS toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Pregnancy category D with prolonged use or high doses at term; caution in patients with head injuries, may increase respiratory depression and CSF pressure; caution postoperatively and in patients with history of pulmonary disease (suppresses cough reflex); increased doses due to tolerance may aggravate or cause seizures (even without prior history); caution in patients with renal dysfunction (decrease dose), do not use in patients with severe renal dysfunction, normeperidine metabolite accumulation may induce CNS toxicity

Drug Name	Hydromorphone (Dilaudid) -- 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).
Adult Dose	1-2 mg IV/IM/SC q4h; adjust dose according to pain scale assessment
Pediatric Dose	Not established; problem rare <20>
Contraindications	Documented hypersensitivity; do not use for obstetrical analgesia, increased intracranial pressure, or respiratory depression; ulcerative colitis; Crohn disease; relative contraindications include abdominal cramping and distention
Interactions	Additive sedation and respiratory depression with other drugs causing CNS depression; drugs inducing CYP450 metabolism (eg, rifampin, phenytoin, carbamazepine) may decrease hydromorphone effect
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Pregnancy category D with prolonged use or high doses at term; caution in patients with head injuries, may increase respiratory depression and CSF pressure; caution postoperatively and in patients with history of pulmonary disease (suppresses cough reflex); caution in patients with impaired hepatic function (decrease dose), hypothyroidism, Crohn disease, ulcerative colitis, Addison disease, or prostatic hypertrophy

Drug Name	Ibuprofen (Motrin, Advil, Ibuprin) -- Indicated for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult Dose	Mild to moderate pain: 400 mg PO q4-6h prn; not to exceed 3.2 g/d; IM dosing for those with concurrent nausea
Pediatric Dose	Not established; problem rare <20>
Contraindications	Documented hypersensitivity; active peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Interactions	Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and possibly toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase methotrexate toxicity; phenytoin levels may increase when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; caution in patients with congestive heart failure, hypertension, and decreased renal and hepatic function; caution in patients with coagulation abnormalities or during anticoagulant therapy

Drug Name	Ketorolac (Toradol) -- Inhibits prostaglandin synthesis by decreasing activity of cyclooxygenase, which results in decreased formation of prostaglandin precursors.
Adult Dose	30-60 mg IM initially, followed by 15-30 mg q6h; alternatively 15-30 mg IV initially, followed by 15-30 mg IV prn; not to exceed 120 mg/d (60 mg/d in renal failure, >65 y, or <50>
Pediatric Dose	Not established; problem rare <20>
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding; do not administer into CNS
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and possibly toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Category D in third trimester of pregnancy; may cause acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; leukopenia (rare) usually returns to normal during ongoing therapy; discontinue therapy if persistent leukopenia, granulocytopenia, or thrombocytopenia occur; decrease dose in renal failure, >65 y, or <50>

Drug Category: Antiemetic agents -- 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.

Drug Name	Metoclopramide (Reglan) -- 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.
Adult Dose	10 mg IV q6h prn
Pediatric Dose	Not established; problem rare <20>
Contraindications	Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders
Interactions	Opioid analgesics may increase toxicity in CNS; may cause additive effect with other drugs that cause extrapyramidal reactions; hypertension observed with coadministration of MAOIs, tricyclic antidepressants, or sympathomimetics; may increase serum levels of cyclosporine, sirolimus, or tacrolimus; may decrease digoxin serum levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in breastfeeding women, patients with depression, hypertension, Parkinson disease, and conditions aggravated by anticholinergic or antidopaminergic effects; may cause tardive dyskinesia

Drug Name	Prochlorperazine (Compazine) -- May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system.
Adult Dose	5-10 mg PO/IM tid/qid; not to exceed 40 mg/d; alternatively, 2.5-10 mg IV q3-4h prn; not to exceed 10 mg/dose or 40 mg/d 25 mg PR bid
Pediatric Dose	Not established; problem rare <20>
Contraindications	Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe hypotension; children <2>
Interactions	Coadministration with other CNS depressants or anticonvulsants may cause additive effects
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Drug-induced Parkinson syndrome or pseudoparkinsonism occurs frequently, akathisia is most common extrapyramidal reaction in elderly persons; tardive dyskinesia may occur, especially in elderly persons (up to 40%); extrapyramidal effects most pronounced in children <5>

Drug Name	Ondansetron (Zofran) -- 5-HT-3 receptor antagonist used when other classes fail or are contraindicated.
Adult Dose	4 mg IV q6h prn; 8 mg PO tid prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Although potential exists for cytochrome P-450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to change half-life and clearance, dosage adjustment usually not required
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in impaired liver function; medication administered for prevention of nausea and vomiting, not for rescue of nausea and vomiting