Appendicitis, Acute

Last Updated: June 9, 2004 Rate this Article

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Synonyms and related keywords: acute inflammation of the appendix, abdominal pain

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Author: Sandy Craig, MD, Associate Program Director, Adjunct Assistant Professor, Department of Emergency Medicine, University of North Carolina at Chapel Hill, Carolinas Medical Center Sandy Craig, MD, is a member of the following medical societies: Alpha Omega Alpha, and Society for Academic Emergency Medicine Editor(s): William Lober, MD, Instructor, Department of Medical Education, Division of Biomedical and Health Informatics, University of Washington School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; Eugene Hardin, MD, Chair, Department of Emergency Medicine, Martin Luther King Jr/Charles R Drew Medical Center; Medical Director, Hubert H Humphrey Comprehensive Health Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Instructor, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School

  INTRODUCTION Section 2 of 11   

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Background: Appendicitis is a common and urgent surgical illness with protean manifestations, generous overlap with other clinical syndromes, and significant morbidity, which increases with diagnostic delay. No single sign, symptom, or diagnostic test accurately makes the diagnosis of appendiceal inflammation in all cases. The surgeon's goals are to evaluate a relatively small population of patients referred for suspected appendicitis and to minimize the negative appendectomy rate without increasing the incidence of perforation. The emergency physician must evaluate the larger group of patients who present to the ED with abdominal pain of all etiologies with the goal of approaching 100% sensitivity for the diagnosis in a time-, cost-, and consultation-efficient manner.

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Pathophysiology: Obstruction of the appendiceal lumen is the primary cause of appendicitis. Obstruction of the lumen leads to distension of the appendix due to accumulated intraluminal fluid. Ineffective lymphatic and venous drainage allows bacterial invasion of the appendiceal wall and, in advanced cases, perforation and spillage of pus into the peritoneal cavity.

Frequency:

In the US: Appendicitis occurs in 7% of the US population, with an incidence of 1.1/1000 people per year. Some familial predisposition exists.

Internationally: Incidence of appendicitis is lower in cultures with a higher intake of dietary fiber. Dietary fiber is thought to decrease the viscosity of feces, decrease bowel transit time, and discourage formation of fecaliths, which predispose individuals to obstructions of the appendiceal lumen.

Mortality/Morbidity:

Overall mortality rate of 0.2-0.8% is attributable to complications of the disease rather than to surgical intervention.

Mortality rate rises above 20% in patients older than 70 years, primarily because of diagnostic and therapeutic delay.

Perforation rates are higher in patients younger than 18 years and in patients older than 50 years, possibly because of delays in diagnosis. Appendiceal perforation is associated with an increase in morbidity and mortality rates.

Sex: Incidence of appendicitis is approximately 1.4 times greater in men than in women. The incidence of primary appendectomy is approximately equal in both sexes.

Age:

Incidence of appendicitis gradually rises from birth, peaks in the late teen years, and gradually declines in the geriatric years.

Although rare, cases of neonatal and even prenatal appendicitis have been reported.

The emergency physician must maintain a high index of

Widow

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suspicion in all age groups.

  CLINICAL Section 3 of 11   

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History:

Variations in the position of the appendix, age of the patient, and degree of inflammation make the clinical presentation of appendicitis notoriously inconsistent. In addition, many other disorders present with symptoms similar to those of appendicitis. These include pelvic inflammatory disease (PID), tubo-ovarian abscess, endometriosis, ovarian cyst or torsion, degenerating uterine leiomyomata, diverticulitis, Crohn disease, colonic carcinoma, rectus sheath hematoma, cholecystitis, bacterial enteritis, mesenteric adenitis, and omental torsion.

The classic history of anorexia and periumbilical pain followed by nausea, right lower quadrant (RLQ) pain, and vomiting occurs in only 50% of cases.

Migration of pain from the periumbilical area to the RLQ is the most discriminating historical feature, with sensitivity and specificity of approximately 80%.

When vomiting occurs, it nearly always follows the onset of pain. Vomiting that precedes pain is suggestive of intestinal obstruction, and the diagnosis of appendicitis should be reconsidered.

Nausea is present in 61-92% of cases; anorexia is present in 74-78% of cases. Neither finding is statistically different from findings in ED patients with other etiologies of abdominal pain.

Diarrhea or constipation is noted in as many as 18% of patients and should not be used to discard the possibility of appendicitis.

Duration of symptoms is less than 48 hours in approximately 80% of adults but tends to be longer in the elderly and in those with perforation. Approximately 2% of patients report duration of pain in excess of 2 weeks.

History of prior similar pain is reported in as many as 23% of cases. History of similar pain should not, in and of itself, be used

to discard the possibility of appendicitis.

An inflamed appendix located in proximity to the urinary bladder or ureter can give rise to irritative voiding symptoms and hematuria or pyuria. Remember that cystitis in males is rare in the absence of instrumentation. Consider the possibility of an inflamed pelvic appendix in males with apparent cystitis.

Physical:

RLQ tenderness is present in 96% of patients but is a very nonspecific finding.

The most specific physical findings are rebound tenderness, pain on percussion, rigidity, and guarding.

Rovsing sign (ie, RLQ pain with palpation of the LLQ), obturator sign (ie, RLQ pain with internal rotation of the flexed right hip), and psoas sign (ie, RLQ pain with hyperextension of the right hip) are present in a minority of patients with acute appendicitis. Their absence never should be used to rule out appendiceal inflammation.

A positive cough sign (ie, sharp pain in the RLQ elicited by a voluntary cough) may be helpful in making the clinical diagnosis of localized peritonitis. Similarly, RLQ pain in response to percussion of a remote quadrant of the abdomen, or to firm percussion of the patient's heel, suggests peritoneal inflammation.

Literature is inconsistent as to whether rectal examination is helpful in making the diagnosis; however, failure to perform a rectal examination is cited frequently in successful malpractice claims.

Causes:

Appendicitis is usually precipitated by obstruction of the appendiceal lumen. Causes of luminal obstruction include fecaliths, lymphoid follicle hyperplasia, foreign bodies (eg, shotgun pellet, intrauterine device), and tumors.

o Fecaliths form when calcium salts and fecal debris become layered around a nidus of inspissated fecal material located within the appendix.

o Lymphoid hyperplasia is associated with a variety of inflammatory and infectious disorders including Crohn disease, gastroenteritis, amebiasis, respiratory infections, measles, and mononucleosis.

  DIFFERENTIALS Section 4 of 11   

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Cholecystitis and Biliary Colic Constipation Diverticular Disease Endometriosis Gastroenteritis Inflammatory Bowel Disease Mesenteric Ischemia Ovarian Cysts Ovarian Torsion Pediatrics, Intussusception Pelvic Inflammatory Disease Spider Envenomations, Widow

Other Problems to be Considered:

TyphilitisEpiploic appendagitisMesenteric adenitis

  WORKUP Section 5 of 11   

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Lab Studies:

Complete blood count

o Studies consistently show that 80-85% of adults with appendicitis have a WBC count greater than 10,000. Neutrophilia greater than 75% occurs in 78% of patients. Fewer than 4% of patients with appendicitis have a WBC count less than 10,000 and neutrophilia less than 75%.

o CBC is inexpensive, rapid, and widely available; however, it is nonspecific and misses 4% of cases. It costs approximately $50.

o Literature is inconsistent with regard to WBC count parameters in children and elderly patients with appendicitis.

C-reactive protein test

o C-reactive protein (CRP) is an acute-phase reactant synthesized by the liver in response to bacterial infection. Serum levels begin to rise within 6-12 hours of acute tissue inflammation. A rapid assay is widely available.

o Several prospective studies have concluded that in adult patients who have had symptoms for longer than 24 hours, a normal CRP has a negative predictive value of approximately 100% for the presence of appendicitis. Specificity has ranged from 50-87% in several series. Two other studies in adults found that a combination of a WBC count of less than 10,500, neutrophilia less than 75%, and a normal CRP had 100% negative predictive value for the diagnosis of acute appendicitis. In 1989, Thimsen et al noted that a normal CRP after 12 hours of symptoms was 100% predictive of benign, self-limited illness.

o CRP does not distinguish between various types of bacterial infection.

o Cost is approximately $66.

Imaging Studies:

Computed tomography o Abdominal CT has become the most important imaging study in the evaluation of

patients with atypical presentations of appendicitis. Several studies have shown a decrease in negative laparotomy rate and appendiceal perforation rate when abdominal CT is used in selected patients with suspected appendicitis. Advantages of CT scanning include superior sensitivity and accuracy compared with other imaging techniques, ready availability, noninvasiveness, and potential to reveal alternative diagnoses. Disadvantages include radiation exposure, potential for anaphylactoid reaction if intravenous (IV) contrast is used, lengthy acquisition time if oral contrast is used, and patient discomfort if rectal contrast is used. A variety of CT techniques have been studied.

o Initial studies evaluated sequential (nonhelical) CT scanning in the diagnosis of appendicitis. Malone, in 1993, evaluated unenhanced, sequential CT scanning in 211 patients and reported a sensitivity of 87% and specificity of 97%. Addition of IV and oral contrast increases sensitivity to 96-98%, but it increases cost to approximately $900. Sequential CT with oral and IV contrast is highly accurate but time consuming and expensive; it is best used for equivocal presentations when helical CT is not available.

o In 1997, Lane evaluated helical CT scanning without contrast and found a sensitivity of 90% and specificity of 97%. More recent studies (Lane, 1999; Ege,

2002) of noncontrast helical CT in adult patients with suspected appendicitis found the sensitivity to be 96% and the specificity to be 98-99%.

o Rao, in 1997, found that focused (lower abdomen and upper pelvis) helical CT scanning with 3% Gastrografin contrast instilled into the colon (without IV contrast) has a superior sensitivity of 98% and specificity of 98%. Focused helical scanning with avoidance of IV contrast eliminates the risk of anaphylactoid contrast reaction and reduces the cost to approximately $230. Acquisition time is less than 15 minutes. Radiation exposure is less than that of a standard obstruction series. Alternative diagnoses are revealed in up to 62% of patients and include diverticulitis, nephrolithiasis, adnexal pathology, RLQ tumor, small bowel hernias, and ischemia.

o Current literature suggests that limited helical CT with rectal contrast is a highly accurate, time-efficient, cost-effective way to evaluate adult patients with equivocal presentations for appendicitis. Two studies of focused helical CT in children suggest sensitivity of 95-97% in that population. Continued improvements in helical CT technology and interpretation may allow noncontrast helical CT to be the imaging test of choice in the future.

Ultrasonography

o In 1986, Puylaert described a graded compression technique for evaluation of the appendix using transabdominal ultrasonography. A 5-MHz transducer is used, applying gentle but firm pressure in the RLQ to displace intervening bowel gas and to decrease the distance between the transducer and the appendix, thereby improving image quality. An outer diameter of greater than 6 mm, noncompressibility, lack of peristalsis, or presence of a periappendiceal fluid collection characterizes an inflamed appendix. The normal appendix is not visualized in most cases. A posterolateral approach is suggested to evaluate the retrocecal area. Scattered case reports endorse transvaginal ultrasonography for women with low pelvic tenderness if the appendix is not visualized on transabdominal sonography.

o Numerous studies have documented a sensitivity of 85-90% and a specificity of 92-96%. Five studies using graded compression ultrasonography in children reported sensitivities of 85-95% and specificities ranging from 47-96%. The cost is approximately $225.

o Advantages include noninvasiveness, short acquisition time, lack of radiation exposure, and potential for diagnosis of other causes of abdominal pain, particularly in the subset of females of childbearing age. Many authorities feel that ultrasonography should be the initial imaging test in pregnant women and in pediatric patients because radiation exposure is particularly undesirable in those groups.

o The principal disadvantage is that ultrasonographic examination is operator dependent. Because nonvisualization is interpreted as a noninflamed appendix,

technical expertise and commitment to a thorough examination are essential in obtaining maximum sensitivity.

o If graded compression ultrasonography of the right lower quadrant is positive for appendicitis, appendectomy should be performed. If negative, this finding is not sufficiently sensitive to rule out the possibility of appendicitis. Consideration should be given to further observation and focused helical CT with rectal contrast.

Abdominal radiography o Kidneys-ureters-bladder (KUB) view used typically. o Visualization of an appendicolith in a patient with symptoms consistent with

appendicitis is highly suggestive of appendicitis, but this occurs in fewer than 10% of cases.

o The consensus in the literature is that plain radiography is insensitive, nonspecific, and not cost-effective.

Barium enema

o A single contrast study can be performed on an unprepared bowel. Nonfilling or incomplete filling of the appendix coupled with pressure effect or spasm in the cecum suggests appendicitis. The cost is approximately $420.

o Multiple studies have found that the sensitivity of a barium enema is in the range of 80-100%. However, as many as 16% of examinations in adults (and 22-39% of examinations in children) were technically unsuitable for interpretation and were excluded from data analysis.

o Advantages of barium enema are its wide availability, use of simple equipment, and potential for diagnosis of other diseases (eg, Crohn disease, colon cancer, ischemic colitis) that may mimic appendicitis.

o Disadvantages include its high incidence of nondiagnostic examination, radiation exposure, insufficient sensitivity, and invasiveness. These disadvantages make barium enema a poor screening examination for use by emergency physicians. Barium enema has essentially no role in the diagnosis of acute appendicitis in the era of ultrasonography and CT.

Radionuclide scanning

o Whole blood is withdrawn. Neutrophils and macrophages are labeled with technetium 99m albumin and administered intravenously. Images of the abdomen and pelvis are obtained serially over 4 hours. Localized uptake of tracer in the RLQ suggests appendiceal inflammation. The cost is approximately $450.

o Four early studies in adults with suspected appendicitis showed a sensitivity of 90% and specificity of 92-96%. Two recent studies of newer labeling techniques achieved sensitivities of 98% for the presence of appendicitis.

o While future studies may confirm sensitivity as high as 98%, the acquisition time of 5 hours and the lack of availability are disadvantages to its use as a high-sensitivity ED screen for appendicitis.

Other Tests:

Clinical diagnostic scores

o Several investigators have created diagnostic scoring systems in which a finite number of clinical variables is elicited from the patient and each is given a numerical value. The sum of these values is used to predict the likelihood of acute appendicitis.

o The best known of these is the MANTRELS score, which tabulates presence or absence of migration of pain, anorexia, nausea/vomiting, tenderness in the RLQ, rebound tenderness, elevated temperature, leukocytosis, and shift to the left.

o Clinical scoring systems are attractive because of their simplicity; however, none has been shown prospectively to improve upon physician judgment in the subset of patients evaluated in the ED for abdominal pain suggestive of appendicitis. The MANTRELS score, in fact, was based on a population of patients hospitalized for suspected appendicitis, which differs markedly from the population seen in the ED.

Computer-aided diagnosis

o A retrospective database of clinical features of patients with appendicitis and other causes of abdominal pain is entered into a computer. It is then utilized in prospectively assessing the risk of appendicitis.

o Computer-aided diagnosis can achieve sensitivity greater than 90% while reducing rates of perforation and negative laparotomy by as much as 50%.

o The principle disadvantages are that each institution must generate its own unique database to reflect local population characteristics. Specialized equipment and significant initiation time are required.

o Computer-aided diagnosis is not widely available in US emergency departments.

  TREATMENT Section 6 of 11   

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Emergency Department Care:

Treatment guidelines for patients with suspected acute appendicitis include the following:

o Establish IV access and administer aggressive crystalloid therapy to patients with clinical signs of dehydration or septicemia.

o Do not give anything by mouth to patients with suspected appendicitis.

o Administration of analgesics to patients with acute undifferentiated abdominal pain has historically been discouraged and criticized because of concerns that they would render the physical examination less reliable. At least 8 randomized controlled studies now report that administering opioid analgesic medications to adult and pediatric patients with acute undifferentiated abdominal pain is safe; no study has found that analgesics adversely effect the accuracy of the physical examination.

o Consider ectopic pregnancy in women of childbearing age and obtain a qualitative beta-hCG in all cases.

o Administer IV antibiotics to those with signs of septicemia and those who are to proceed to laparotomy.

Nonsurgical treatment of appendicitis

o Anecdotal reports describe the success of IV antibiotics in treating acute appendicitis in patients without access to surgical intervention (eg, submariners, individuals on ships at sea). In one prospective study of 20 patients with ultrasound-proven appendicitis, 95% had resolution of symptoms with antibiotics alone, but 37% of these patients experienced recurrent appendicitis within 14 months.

o This may be useful when appendectomy is not accessible or when it is temporarily a high-risk procedure.

Preoperative antibiotics o Preoperative antibiotics have a demonstrated efficacy in decreasing

postoperative wound infection rates in numerous prospective controlled studies. o Broad-spectrum gram-negative and anaerobic coverage is indicated. o These should be given in conjunction with the surgical consultant.

Consultations:

General surgeon

  MEDICATION Section 7 of 11   

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The goals of therapy are to eradicate the infection and prevent complications.

Drug Category: Antibiotics -- These agents have proven effective in decreasing the rate of postoperative wound infection and in improving outcome in patients with appendiceal abscess or septicemia.

Drug Name

Metronidazole (Flagyl) -- Used in combination with an aminoglycoside, such as gentamicin, provides broad gram-negative and anaerobic coverage. Appears to be absorbed into cells, and intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing cell death.

Adult Dose 7.5 mg/kg IV before surgery

Pediatric Dose15-30 mg/kg/d IV divided bid/tid for 7 d, or 40 mg/kg PO once; not to exceed 2 g/d

Contraindications Documented hypersensitivity

Interactions May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity; disulfiram reaction may occur with orally ingested ethanol

Pregnancy B - Usually safe but benefits must outweigh the risks.

PrecautionsAdjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Drug Name

Gentamicin (Gentacidin, Garamycin) -- Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.Dosing regimens are numerous; adjust dose on the basis of CrCl and changes in volume of distribution. May be given IV/IM.

Adult Dose2 mg/kg IV loading dose before surgery; 3-5 mg/kg/d divided tid/qid thereafter

Pediatric DoseInfants/neonates: 7.5 mg/kg/d IV divided tidChildren: 6-7.5 mg/kg/d IV divided tid

ContraindicationsDocumented hypersensitivity, non–dialysis-dependent renal insufficiency

Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents; thus, prolonged respiratory depression may occur; coadministration with loop diuretics may increase ototoxicity of aminoglycosides, which may cause irreversible hearing loss of varying degrees (monitor regularly)

Pregnancy C - Safety for use during pregnancy has not been established.

Precautions

Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name

Cefotetan (Cefotan) -- Second-generation cephalosporin used as single-drug therapy to provide broad gram-negative coverage and anaerobic coverage. Half-life is 3.5 h. Give with cefoxitin to achieve effectiveness of single-dose.

Adult Dose 2 g IV once before surgery

Pediatric Dose 20-40 mg/kg IV/IM once before surgery

Contraindications Documented hypersensitivity

Interactions

Consumption of alcohol within 72 h of cefotetan may produce disulfiramlike reactions; may increase hypoprothrombinemic effects of anticoagulants; coadministration with potent diuretics (eg, loop diuretics) or aminoglycosides may increase nephrotoxicity

Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions

Reduce dosage by half if CrCl 10-30 mL/min and by three quarters if <10 mL/min; bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy

Drug NameCefoxitin (Mefoxin) -- Second-generation cephalosporin indicated for management of infections caused by susceptible gram-positive cocci and gram-negative rods. Half-life is 0.8 h.

Adult Dose2 g IV before surgery, followed by 3 doses of 2 g q4-6h for 24 h

Pediatric Dose<3 months: Not established>3 months: 30-40 mg/kg IV before surgery, followed by 3 doses of 2 g q4-6h for 24 h

Contraindications Documented hypersensitivity

InteractionsProbenecid may increase effects; coadministration with aminoglycosides or furosemide may increase nephrotoxicity (closely monitor renal function)

Pregnancy B - Usually safe but benefits must outweigh the risks.

PrecautionsBacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged use or repeated treatment; caution in patients with previously diagnosed colitis

Drug Name

Meropenem (Merrem) -- Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective against most gram-positive and gram-negative bacteria.

Adult Dose 1 g IV q8h

Pediatric Dose 40 mg/kg IV q8h

Contraindications Documented hypersensitivity

InteractionsProbenecid may inhibit renal excretion of meropenem, increasing meropenem levels

Pregnancy B - Usually safe but benefits must outweigh the risks.

PrecautionsPseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication

Drug Category: Analgesics -- These agents can be used to relieve acute undifferentiated abdominal pain in patients presenting to the emergency department.

Drug Name

Morphine sulfate (Astramorph, Duramorph, MS Contin, MSIR, Oramorph) -- DOC for analgesia because of reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained.

Adult Dose

Starting dose: 0.1 mg/kg IV/IM/SCMaintenance dose: 5-20 mg/70 kg IV/IM/SC q4hRelatively hypovolemic patients: Start with 2 mg IV/IM/SC; reassess hemodynamic effects of dose

Pediatric DoseInfants and children: 0.1-0.2 mg/kg dose IV/IM/SC q2-4h prn; not to exceed 15 mg/dose; may initiate at 0.05 mg/kg/dose

ContraindicationsDocumented hypersensitivity; hypotension; potentially compromised airway in which establishing rapid airway control would be difficult

Interactions Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, and other CNS

depressants may potentiate adverse effects of morphine

Pregnancy C - Safety for use during pregnancy has not been established.

Precautions

Caution in hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate

  FOLLOW-UP Section 8 of 11   

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Further Inpatient Care:

Open versus laparoscopic appendectomy

o Initially performed in 1987, laparoscopic appendectomy has been performed in thousands of patients and is successful in 90-94% of attempts.

o Advantages of laparoscopic appendectomy include increased cosmetic satisfaction and a decrease in the postoperative wound infection rate. Some studies find a shorter convalescent period compared to open appendectomy and a trend toward shorter hospital stays.

o Disadvantages of laparoscopic appendectomy include a slightly longer operating time (approximately 20 min) and increased cost.

o Contraindications to laparoscopic appendectomy include significant intra-abdominal adhesions and pregnancy beyond the first trimester.

Complications:

Wound infection

Dehiscence

Bowel obstruction

Abdominal/pelvic abscess

Death (rare)

Prognosis:

Excellent

Patient Education:

For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles, Appendicitis and Abdominal Pain in Adults.

  MISCELLANEOUS Section 9 of 11   

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Medical/Legal Pitfalls:

Approximately 10% of adults who develop appendicitis are not diagnosed correctly at the first physician encounter. Failure to diagnose appendicitis is the leading cause of successful malpractice claims and the fifth most expensive source of claims against emergency physicians.

Special Concerns:

Pregnancy

o The incidence of appendicitis is unchanged in pregnancy, but the clinical presentation becomes even more variable. During pregnancy the appendix migrates in a counterclockwise direction toward the right kidney, rising above the iliac crest at about 4.5 months gestation. RLQ pain and tenderness dominate in the first trimester, but in the latter half of pregnancy, right upper quadrant (RUQ) or right flank pain must be looked upon as a possible sign of appendiceal inflammation. Nausea, vomiting, and anorexia are common in uncomplicated first trimester pregnancies, but their reappearance later in gestation should be viewed with suspicion.

o Physiologic leukocytosis during pregnancy makes the WBC count less useful in the diagnosis, and no reliable distinguishing WBC parameters are cited in the literature. One study of 22 pregnant women in the first and second trimesters found that graded compression ultrasound had a sensitivity of 66% and specificity of 95%. Diagnostic laparoscopy also has been suggested for pregnant patients in the first trimester with suspected appendicitis.

o While negative appendectomy does not appear to affect maternal or fetal health adversely, diagnostic delay with perforation does increase fetal and maternal morbidity. Therefore, aggressive evaluation of the appendix is warranted in this group.

Nonpregnant women of childbearing age

o Patients in this group who develop appendicitis are misdiagnosed in 33% of cases. The most frequent misdiagnoses are PID, followed by gastroenteritis and urinary tract infection.

o In distinguishing appendiceal pain from PID, presence of anorexia and onset of pain more than 14 days after menses favors appendicitis. Previous PID, presence of vaginal discharge, or presence of urinary symptoms indicates the diagnosis of PID.

o On physical examination, tenderness outside the RLQ, cervical motion tenderness, vaginal discharge, and positive urinalysis favor the diagnosis of PID.

Children

o Children with appendicitis are misdiagnosed in 25-30% of cases overall, and the rate of initial misdiagnosis is inversely related to the age of the patient.

o The most common misdiagnosis is gastroenteritis, followed by upper respiratory infection and lower respiratory infection.

o Misdiagnosed children are more likely than their correctly diagnosed counterparts to have vomiting before pain onset, diarrhea, constipation, dysuria, signs and symptoms of upper respiratory infection, and lethargy or irritability.

o Physical findings less likely to be documented in the children who are misdiagnosed include findings of ear, nose, and throat exam; bowel sounds; peritoneal signs; and findings of rectal examination.

Elderly patients

o Appendicitis in patients older than 60 years accounts for 10% of all appendectomies.

o The incidence of misdiagnosis is increased in the elderly. o In those patients with comorbid conditions, diagnostic delay does correlate with

increased morbidity and mortality. o Older patients tend to seek medical attention later in the course of illness;

therefore, duration of symptoms in excess of 24-48 hours should not dissuade the physician from the diagnosis.

  PICTURES Section 10 of 11   

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Caption: Picture 1. CT scan with colonic contrast reveals an enlarged appendix with thickened walls, which do not fill with contrast, lying adjacent to the right psoas muscle.

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Picture Type: CTCaption: Picture 2. Graded compression transabdominal ultrasound shows a sagittal view of an acutely inflamed appendix. The tubular structure is noncompressible, lacks peristalsis, and measures greater than 6 mm in diameter. A thin rim of periappendiceal fluid is present.

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Picture Type: PhotoCaption: Picture 3. Graded compression transabdominal ultrasound shows a transverse view of an acutely inflamed appendix. Note the targetlike appearance due to thickened wall and surrounding loculated fluid collection.

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Picture Type: PhotoCaption: Picture 4. Kidneys-ureters-bladder (KUB) x-ray shows an appendicolith in the right lower quadrant. This is seen in fewer than 10% of patients with appendicitis but, when present, is essentially pathognomonic.

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Picture Type: X-RAYCaption: Picture 5. Technetium 99m radionuclide scan of the abdomen shows focal uptake of labeled white blood cells in the right lower quadrant consistent with acute appendicitis.

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Acute Appendicitis: Review and Update D. MIKE HARDIN, JR., M.D.,

Texas A&M University Health Science Center, Temple, Texas

Appendicitis is common, with a lifetime occurrence of 7 percent. Abdominal pain and anorexia are the predominant symptoms. The most important physical examination finding is right lower quadrant tenderness to palpation. A complete blood count and urinalysis are sometimes helpful in determining the diagnosis and supporting the presence or absence of appendicitis, while appendiceal computed tomographic scans and ultrasonography can be helpful in equivocal cases. Delay in diagnosing appendicitis increases the risk of perforation and complications. Complication and mortality rates are much higher in children and the elderly. (Am Fam Physician 1999;60:2027-34.)

Appendicitis is the most common acute surgical condition of the abdomen.1 Approximately 7 percent of the population will have appendicitis in their lifetime,2 with the peak incidence occurring between the ages of 10 and 30 years.3

Despite technologic advances, the diagnosis of appendicitis is still based primarily on the patient's history and the physical examination. Prompt diagnosis and surgical referral may reduce the risk of perforation and prevent complications.4 The mortality rate in nonperforated appendicitis is less than 1 percent, but it may be as high as 5 percent or more in young and elderly patients, in whom diagnosis may often be delayed, thus making perforation more likely.1

Pathogenesis

The appendix is a long diverticulum that extends from the inferior tip of the cecum.5 Its lining is interspersed with lymphoid follicles.3 Most of the time, the appendix has an intraperitoneal location (either anterior or retrocecal) and, thus, may come in contact with the anterior parietal peritoneum when it is inflamed. Up to 30 percent of the time, the appendix may be "hidden" from the anterior peritoneum by being in a pelvic, retroileal or retrocolic (retroperitoneal retrocecal) position.6 The "hidden" position of the appendix notably changes the clinical manifestations of appendicitis.

Obstruction of the narrow appendiceal lumen initiates the clinical illness of acute appendicitis. Obstruction has multiple causes, including lymphoid hyperplasia (related to viral illnesses, including upper respiratory infection, mononucleosis, gastroenteritis), fecaliths, parasites, foreign bodies, Crohn's disease, primary or

TABLE 1 Common Symptoms of Appendicitis

Common symptoms* Frequency (%)

Abdominal pain ~100Anorexia ~100Nausea   90Vomiting   75Pain migration   50Classic symptom sequence (vague periumbilical pain to anorexia/nausea/unsustained vomiting to migration of pain to right lower quadrant to low-grade fever)

  50

*--Onset of symptoms typically within past 24 to 36 hours.Information from references 3 through 5.

metastatic cancer and carcinoid syndrome. Lymphoid hyperplasia is more common in children and young adults, accounting for the increased incidence of appendicitis in these age groups.1,5

History and Physical Examination

Abdominal pain is the most common symptom of appendicitis.3 In multiple studies,3-5 specific characteristics of the abdominal pain and other associated symptoms have proved to be reliable indicators of acute appendicitis (Table 1). A thorough review of the history of the abdominal pain and of the patient's recent genitourinary, gynecologic and pulmonary history should be obtained.

Anorexia, nausea and vomiting are symptoms that are commonly associated with acute appendicitis. The classic history of pain beginning in the periumbilical region and migrating to the right lower quadrant occurs in only 50 percent of patients.1 Duration of symptoms exceeding 24 to 36 hours is uncommon in nonperforated appendicitis.1

TABLE 2 Significant Likelihood Ratios for Symptoms and Signs of Acute Appendicitis

Symptom/sign Positive likelihood ratio (LR+) Symptom/sign

Negative likelihoodratio (LR-)

Right lower quadrant (RLQ) pain

8.0 RLQ pain§ 0 to 0.28†

Pain migration 3.2 No similar pain previously||

0.3

Pain before vomiting

2.8 Pain migration 0.5

Anorexia, nausea and vomiting*

Much lower LR+ than RLQ pain, pain migration and pain before vomiting

Guarding 0 to 0.54†

Rigidity 3.76 Rebound tenderness

0 to 0.86†

Psoas sign 2.38 Fever, rigidity and psoas sign¶

Rebound tenderness

1.1 to 6.3†

Fever 1.9‡

Guarding and rectal tenderness*

Much lower LR+ than rigidity, psoas sign and

rebound tenderness

NOTE: LR is the amount by which the odds of a disease change with new information, as follows: Likelihood ratio  Degree of change in probability

>10 or <0.1  Large (often conclusive)

5 to 10 or 0.1 to 0.2  Moderate

2 to 5 or 0.2 to 0.5  Small (but sometimes important)

1 to 2 or 0.5 to 1  Small (rarely important)

*--These symptoms and signs have much lower LR+.†--Ratios are presented in ranges for signs and symptoms that had widely varying results in studies.‡--Fever had only borderline LR+.§--That is, the absence of RLQ pain significantly lowers the odds of having appendicitis.||--That is, the history of experiencing a similar pain previously lowers the odds of having appendicitis.¶--These signs have higher LR-.Information from references 7, 8 and 19

In a recent meta-analysis,7 likelihood ratios were calculated for many of these symptoms (Table 2). A likelihood ratio is the amount by which the odds of a disease change with new information (e.g., physical examination findings, laboratory results).8 This change can be positive or negative. Symptoms such as anorexia, nausea and vomiting commonly occur in acute appendicitis; however, the presence of these symptoms does not necessarily increase the likelihood of appendicitis nor does their absence decrease the likelihood of the diagnosis. Moreover, other symptoms have more notable positive and negative likelihood ratios (Table 2).

A careful, systematic examination of the abdomen is essential. While right lower quadrant tenderness to palpation is the most important

TABLE 3 Common Signs of Appendicitis

• Right lower quadrant pain on palpation (the single most important sign) • Low-grade fever (38°C [or 100.4°F])--absence of fever or high fever can occur • Peritoneal signs • Localized tenderness to percussion • Guarding • Other confirmatory peritoneal signs (absence of these signs does not exclude appendicitis) • Psoas sign--pain on extension of right thigh (retroperitoneal retrocecal appendix) • Obturator sign--pain on internal rotation of right thigh (pelvic appendix) • Rovsing's sign--pain in right lower quadrant with palpation of left lower quadrant • Dunphy's sign--increased pain with coughing

• Flank tenderness in right lower quadrant (retroperitoneal retrocecal appendix) • Patient maintains hip flexion with knees drawn up for comfort

Information from references 3 through 5.

physical examination finding, other signs may help confirm the diagnosis (Table 3). The abdominal examination should begin with inspection followed by auscultation, gentle palpation (beginning at a site distant from the pain) and, finally, abdominal percussion. The rebound tenderness that is associated with peritoneal irritation has been shown to be more accurately identified by percussion of the abdomen than by palpation with quick release.1

As previously noted, the location of the appendix varies. When the appendix is hidden from the anterior peritoneum, the usual symptoms and signs of acute appendicitis may not be present. Pain and tenderness can occur in a location other than the right lower quadrant.6 A retrocecal appendix in a retroperitoneal location may cause flank pain. In this case, stretching the iliopsoas muscle can elicit pain. The psoas sign is elicited in this manner: the patient lies on the left side while the examiner extends the patient's right thigh (Figures 1a and 1b). In contrast, a patient with a pelvic appendix may show no abdominal signs, but the rectal examination may elicit tenderness in the cul-de-sac. In addition, an obturator sign (pain on passive internal rotation of the flexed right thigh) may be present in a patient with a pelvic appendix3 (Figures 2a and 2b).

FIGURE 1A. The psoas sign. Pain on passive extension of the right thigh. Patient lies on left side. Examiner extends patient's right thigh while applying counter resistance to the right hip (asterisk).

FIGURE 2A. The obturator sign. Pain on passive internal rotation of the flexed thigh. Examiner moves lower leg laterally while applying resistance to the lateral side of the knee (asterisk) resulting in internal rotation of the femur.

FIGURE 1B. Anatomic basis for the psoas sign: inflamed appendix is in a retroperitoneal location in contact with the psoas muscle, which is stretched by this maneuver.

FIGURE 2B. Anatomic basis for the obturator sign: inflamed appendix in the pelvis is in contact with the obturator internus muscle, which is stretched by this maneuver.

The differential diagnosis of appendicitis is broad, but the patient's history and the remainder of the physical examination may clarify the diagnosis (Table 4). Because many gynecologic conditions can mimic appendicitis, a pelvic examination should be performed on all women with abdominal pain. Given the breadth of the differential diagnosis, the pulmonary, genitourinary and rectal examinations are equally important. Studies have shown, however, that the rectal examination provides useful information only when the diagnosis is unclear and, thus, can be reserved for use in such cases.5

Laboratory and Radiologic Evaluation

If the patient's history and the physical examination do not clarify the diagnosis, laboratory and radiologic evaluations may be helpful. A clear diagnosis of appendicitis obviates the need for further testing and should prompt immediate surgical referral.

Laboratory TestsThe white blood cell (WBC) count is elevated (greater than 10,000 per mm3 [100 3 109 per L]) in 80 percent of all cases of acute appendicitis.9 Unfortunately, the WBC is elevated in up to 70 percent of patients with other causes of right lower quadrant pain.10 Thus, an elevated WBC has a low predictive value. Serial WBC measurements (over 4 to 8 hours) in suspected cases may increase the specificity, as the WBC count often increases in acute appendicitis (except in cases of perforation, in which it may initially fall).5

In addition, 95 percent of patients have neutrophilia1 and, in the elderly, an elevated band count greater than 6 percent has been shown to have a high predictive value for appendicitis.9 In general, however, the WBC count and differential are only moderately helpful in confirming the diagnosis of appendicitis because of their low specificities.

A more recently suggested laboratory evaluation is determination of the C-reactive protein level. An elevated C-reactive protein level (greater than 0.8 mg per dL) is common in appendicitis, but studies disagree on its sensitivity and specificity.4,5 An elevated C-reactive protein level in combination with an elevated WBC count and neutrophilia are highly sensitive (97 to 100 percent). Therefore, if all three of these findings are absent, the chance of appendicitis is low.5

In patients with appendicitis, a urinalysis may demonstrate changes such as mild pyuria, proteinuria and hematuria,1 but the test serves more to exclude urinary

TABLE 4 Differential Diagnosis of Acute Appendicitis

Gastrointestinal

Abdominal pain, cause unknown Cholecystitis Crohn's disease Diverticulitis Duodenal ulcer Gastroenteritis Intestinal obstruction Intussusception Meckel's diverticulitis Mesenteric lymphadenitisNecrotizing enterocolitis Neoplasm (carcinoid, carcinoma, lymphoma) Omental torsion Pancreatitis Perforated viscus Volvulus

Gynecologic Ectopic pregnancy Endometriosis

Ovarian torsion Pelvic inflammatory disease Ruptured ovarian cyst (follicular, corpus luteum) Tubo-ovarian abscess SystemicDiabetic ketoacidosis Porphyria Sickle cell disease Henoch-Schönlein purpura

Pulmonary Pleuritis Pneumonia (basilar) Pulmonary infarction GenitourinaryKidney stone Prostatitis Pyelonephritis Testicular torsion Urinary tract infection Wilms' tumor OtherParasitic infection Psoas abscess Rectus sheath hematoma

Reprinted with permission from Graffeo CS, Counselman FL. Appendicitis. Emerg Med Clin North Am 1996;14:653-71.

tract causes of abdominal pain than to diagnose appendicitis.

Radiologic EvaluationThe options for radiologic evaluation of patients with suspected appendicitis have expanded in recent years, enhancing and sometimes replacing previously used radiologic studies.

Plain radiographs, while often revealing abnormalities in acute appendicitis, lack specificity and are more helpful in diagnosing other causes of abdominal pain. Likewise, barium enema is now used infrequently because of the advances in abdominal imaging.5

Ultrasonography and computed tomographic (CT) scans are helpful in evaluating patients with suspected appendicitis.11 Ultrasonography is appropriate in patients in which the diagnosis is equivocal by history and physical examination. It is especially well suited in evaluating right lower quadrant or pelvic pain in pediatric and female patients. A normal appendix (6 mm or less in diameter) must be identified to rule out appendicitis. An inflamed appendix usually measures greater than 6 mm in diameter (Figure 3), is noncompressible and tender with focal compression. Other right lower quadrant conditions such as inflammatory bowel disease, cecal diverticulitis, Meckel's diverticulum, endometriosis and pelvic inflammatory disease can cause false-positive ultrasonography results.12

FIGURE 3. Ultrasonogram showing longitudinal section (arrows) of inflamed appendix.

CT, specifically the technique of appendiceal CT, is more accurate than ultrasonography (Table 5). Appendiceal CT consists of a focused, helical, appendiceal CT after a Gastrografin-saline enema (with or without oral contrast) and can be performed and interpreted within one hour. Intravenous contrast is unnecessary.12 The accuracy of CT is due in part to its ability to identify a normal appendix better than ultrasonography.13 An inflamed appendix is greater than 6 mm in diameter, but the CT also demonstrates periappendiceal inflammatory changes14 (Figures 4 and 5). If appendiceal CT is not available, standard abdominal/pelvic CT with contrast remains highly useful and may be more accurate than ultrasonography.12

Treatment

The standard for management of nonperforated appendicitis remains appendectomy. Because prompt treatment of appendicitis is important in preventing further morbidity and mortality, a margin of error in over-diagnosis is acceptable. Currently, the national rate of negative appendectomies is approximately 20 percent.15 Some studies have investigated nonoperative management with parenteral antibiotic treatment, but 40 percent of these patients eventually required appendectomy.3

Appendectomy may be performed by laparotomy (usually through a limited right lower quadrant incision) or laparoscopy. Diagnostic laparoscopy may be helpful in equivocal cases or in women of childbearing age, while therapeutic laparoscopy may be preferred in certain subsets of patients (e.g., women, obese patients, athletes).16

While laparoscopic intervention has the advantages of decreased postoperative pain, earlier return to normal activity and better cosmetic results, its disadvantages include greater cost and longer operative time.4 Open

TABLE 5 Comparison of Ultrasound and Appendiceal CT Evaluation of Suspected Appendicitis

Comparison graded ultrasound

Appendiceal computed tomographic scan

Sensitivity 85% 90 to 100%Specificity 92% 95 to 97%Use Evaluate

patients with equivocal diagnosis of appendicitis

Evaluate patients with equivocal diagnosis of appendicitis

Advantages SafeRelatively inexpensiveCan rule out pelvic disease in females Better for children

More accurateBetter identifies phlegmon and abscessBetter identifies normal appendix

Disadvantages Operator dependentTechnically inadequate studies due to gas Pain

CostIonizing radiationContrast

Information from references 11, 13, 20.

appendectomy may remain the primary approach to treatment until further cost and benefit analyses are conducted.

FIGURE 4. Computed tomographic scan showing cross-section of inflamed appendix (A) with appendicolith (a). FIGURE 5. Computed tomographic scan showing enlarged

and inflamed appendix (A) extending from the cecum (C).

Complications

Appendiceal rupture accounts for a majority of the complications of appendicitis. Factors that increase the rate of perforation are delayed presentation to medical care,17 age extremes (young and old)18 and hidden location of appendix.6 A brief period of in-hospital observation (less than six hours) in equivocal cases does not increase the perforation rate and may improve diagnostic accuracy.18

Diagnosis of a perforated appendix is usually easier (although immediately after rupture, the patient's symptoms may temporarily subside). The physical examination findings are more obvious if peritonitis generalizes, with a more generalized right lower quadrant tenderness progressing to complete abdominal tenderness. An ill-defined mass may be felt in the right lower quadrant. Fever is more common with rupture, and the WBC count may elevate to 20,000 to 30,000 per mm3 (200 to 300 3 109 per L) with a prominent left shift.3

A periappendiceal abscess may be treated immediately by surgery or by nonoperative management.4 Nonoperative management consists of parenteral antibiotics with observation or CT-guided drainage, followed by interval appendectomy six weeks to three months later.1

The classic history of pain beginning in the periumbilical region and migrating to the right lower quadrant occurs in only 50 percent of patients.

Special Considerations

While appendicitis is uncommon in young children, it poses special difficulties in this age group. Young children are unable to relate a history, often have abdominal pain from other causes and may have more nonspecific signs and symptoms. These factors contribute to a perforation rate as high as 50 percent in this group.1

In pregnancy, the location of the appendix begins to shift significantly by the fourth to fifth months of gestation. Common symptoms of pregnancy may mimic appendicitis, and the leukocytosis of pregnancy renders the WBC count less useful. While the maternal mortality rate is low, the overall fetal mortality rate is 2 to 8.5 percent, rising to as high as 35 percent in perforation with generalized peritonitis. As in nonpregnant patients, appendectomy is the standard for treatment.3

Elderly patients have the highest mortality rates. The usual signs and symptoms of appendicitis may be diminished, atypical or absent in the elderly, which leads to a higher rate of perforation. More frequent perforation combined with a higher incidence of other medical problems and less reserve to fight infection contribute to a mortality rate of up to 5 percent or more.1

Final Comment

Prompt diagnosis of appendicitis ensures timely treatment and prevents complications. Because abdominal pain is a common presenting symptom in outpatient care, family physicians serve an important role in the diagnosis of appendicitis. Obvious cases of appendicitis require urgent referral, while equivocal cases warrant further evaluation and, many times, surgical consultation.

The author thanks Glen Cryer, Department of Publications, Scott and White Memorial Hospital, Temple, Tex., for help with the manuscript.

Figures 3 through 5 were provided by Michael L. Nipper, M.D., Department of Radiology, Scott and White Memorial Hospital, Temple, Tex.

The technique of appendiceal computed tomography is more accurate than ultrasonography in confirming the diagnosis of appendicitis.