APPENDICITIS

Introduction
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 confirms 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 department clinician 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.

See Medscape's Gastroenterology Specialty page for more information.

Pathophysiology

Obstruction of the appendiceal lumen is the primary cause of appendicitis. An anatomic blind
pouch, obstruction of the appendiceal 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

United States

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

International

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
 • The 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 rate is higher among patients younger than 18 years and patients older than 50
years, possibly because of delays in diagnosis. Appendiceal perforation is associated with
a sharp increase in morbidity and mortality rates.

Sex

The 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. The median age at appendectomy is 22 years.
• Although rare, neonatal and even prenatal appendicitis have been reported.
• The emergency department clinician must maintain a high index of suspicion in all age
groups.

Clinical
History

• Variations in the position of the appendix, age of the patient, and degree of inflammation
make the clinical presentation of appendicitis notoriously inconsistent.
• It is important to remember that the position of the appendix is variable. Of 100 patients
undergoing 3-D multidetector CT, the base of the appendix was located at McBurney's
point in only 4% of patients. In 36% of patients, the base was within 3 cm of McBurney's
point; in 28%, it was 3-5 cm from McBurney's point; and, in 36% of patients, the base of
the appendix was more than 5 cm from McBurney's point.
• In addition, patients with many other disorders present with symptoms similar to those of
appendicitis. Examples include the following:
o Pelvic inflammatory disease (PID) or tubo-ovarian abscess
o Endometriosis
o Ovarian cyst or torsion
o Ureterolithiasis and renal colic
o Degenerating uterine leiomyomata
o Diverticulitis
o Crohn disease
o Colonic carcinoma
o Rectus sheath hematoma
o Cholecystitis
o Bacterial enteritis
 o Mesenteric adenitis
o 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
feature of the patient's history. This finding has a 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 patients; anorexia is present in 74-78% of patients.
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 elderly persons and in those with perforation. Approximately 2% of patients
report duration of pain in excess of 2 weeks.
• A history of similar pain is reported in as many as 23% of cases. A history of similar
pain, in and of itself, should not be used to rule out the possibility of appendicitis.
• An inflamed appendix near the urinary bladder or ureter can cause irritative voiding
symptoms and hematuria or pyuria. Cystitis in male patients is rare in the absence of
instrumentation. Consider the possibility of an inflamed pelvic appendix in male patients
with apparent cystitis.
• Also consider the possibility of appendicitis in pediatric or adult patients who present
with acute urinary retention.

Physical

• Male infants and children occasionally present with an inflamed hemiscrotum due to
migration of an inflamed appendix or pus through a patent processus vaginalis. This is
often initially misdiagnosed as acute testicular torsion.
• RLQ tenderness is present in 96% of patients, but this is a nonspecific finding. Rarely,
left lower quadrant (LLQ) tenderness has been the major manifestation in patients with
situs inversus or in patients with a lengthy appendix that extends into the LLQ.
• The most specific physical findings are rebound tenderness, pain on percussion, rigidity,
and guarding.
• The Rovsing sign (RLQ pain with palpation of the LLQ) suggests peritoneal irritation in
the right lower quadrant precipitated by palpation at a remote location.
• The obturator sign (RLQ pain with internal or external rotation of the flexed right hip)
suggests that the inflamed appendix is located deep in the right hemipelvis.
• The psoas sign (RLQ pain with extension of the right hip) suggests that an inflamed
appendix is located along the course of the right psoas muscle.
• These signs are present in a minority of patients with acute appendicitis. Their absence
never should be used to rule out appendiceal inflammation.
 • Dunphy's sign (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. The Markle sign, pain elicited in a certain area of
the abdomen when the standing patient drops from standing on toes to the heels with a
jarring landing, is stated in DeGowin's Diagnostic Examination to be very sensitive for
localizing true peritonitis.1
• There is no evidence in the medical literature that the digital rectal examination (DRE)
provides useful information in the evaluation of patients with suspected appendicitis;
however, failure to perform a rectal examination is frequently cited in successful
malpractice claims. In 2008, Sedlak et al studied 577 patients who underwent DRE as
part of an evaluation for suspected appendicitis and found no value as a means of
distinguishing patients with and without appendicitis.2

Causes

• Obstruction of the appendiceal lumen usually precipitates appendicitis.

• The most common causes of luminal obstruction are fecaliths and lymphoid follicle
hyperplasia.
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.
o Obstruction of the appendiceal lumen has less commonly been associated with
parasites (eg, Schistosomes species, Strongyloides species), foreign material (eg,
shotgun pellet, intrauterine device, tongue stud, activated charcoal), tuberculosis,
and tumors.

Differential Diagnoses
Abdominal Abscess Mesenteric
Lymphadenitis

Cholecystitis and Omental Torsion

Biliary Colic

Constipation Ovarian Cysts

Crohn Disease Ovarian Torsion

Diverticular Disease Pediatrics,

Intussusception

Ectopic Pregnancy Pelvic Inflammatory

Disease

Endometriosis Renal Calculi

Gastroenteritis Spider Envenomations,
Widow

Gastroenteritis, Urinary Tract Infection,

Bacterial Female

Inflammatory Bowel Urinary Tract Infection,

Disease Male

Meckel Diverticulum

Mesenteric Ischemia

Other Problems to Be Considered

Appendiceal stump appendicitis

Typhilitis
Epiploic appendagitis
Psoas abscess
Yersiniosis

Workup
Laboratory Studies

Complete blood cell count

Studies consistently show that 80-85% of adults with appendicitis have a WBC count greater
than 10,500 cells/mm3. Neutrophilia greater than 75% occurs in 78% of patients. Fewer than 4%
of patients with appendicitis have a WBC count less than 10,500 cells/mm3 and neutrophilia less
than 75%.

Dueholm et al, in 1989, further delineated the relationship between WBC count and the
likelihood of appendicitis by calculating likelihood ratios for defined intervals of the WBC
count.3

Table 1. WBC Count and Likelihood of Appendicitis

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Table
WBC (X Likelihood Ratio
 10,000) (95% CI*)

4-7 0.10 (0-0.39)

7-9 0.52 (0-1.57)

9-11 0.29 (0-0.62)

11-13 2.8 (1.2-4.4)

13-15 1.7 (0-3.6)

15-17 2.8 (0-6.0)

17-19 3.5 (0-10)

19-22 ∞

WBC (X Likelihood Ratio

10,000) (95% CI*)

4-7 0.10 (0-0.39)

7-9 0.52 (0-1.57)

9-11 0.29 (0-0.62)

11-13 2.8 (1.2-4.4)

13-15 1.7 (0-3.6)

15-17 2.8 (0-6.0)

17-19 3.5 (0-10)

19-22 ∞

*CI, confidence interval.

CBC tests are inexpensive, rapid, and widely available; however, the findings are nonspecific.

The literature is inconsistent with regard to WBC counts in children and elderly patients with
appendicitis.

C-reactive protein test

C-reactive protein (CRP) is an acute-phase reactant synthesized by the liver in response to

infection or inflammation. A rapid assay is widely available.
Several prospective studies (Thimsen 1989, Albu 1994, de Carvalho 2003) have shown that, in
adults who have had symptoms for longer than 24 hours, a normal CRP level has a negative
predictive value of 97-100% for appendicitis.4,5

In a 1989 study of 70 patients, Thimsen et al noted that a normal CRP level after 12 hours of
symptoms was 100% predictive of benign, self-limited illness.4

Multiple studies have examined the sensitivity of CRP alone for the diagnosis of appendicitis in
patients selected to undergo appendectomy.

• Gurleyik et al, in 1995, found that 87 of 90 patients with histologically proven

appendicitis had an elevated CRP, a sensitivity of 96.6%.6
• Shakhetrah, in 2000, found that 85 of 89 patients with histologically proven
appendicitis had an elevated CRP, a sensitivity of 95.5%.7
• Asfar et al, in 2000, completed a prospective double blind study of 78
patients undergoing appendectomy and found that CRP had a sensitivity of
93.6%.8
• Erkasap et al, in 2000, prospectively studied the more relevant group of 102
adult patients with RLQ pain, 55 of whom proceeded to appendectomy. In this
group, the sensitivity of CRP was 96%.9

Investigators have also studied the ability of combinations of WBC and CRP to reliably rule out
the diagnosis of appendicitis.

• Gronroos, in 1999, studied 300 patients operated for suspected appendicitis

(200 positive, 100 negative) and found that WBC or CRP was abnormal in all
200 patients with appendicitis.10
• Ortega-Deballon et al, in 2008, prospectively studied patients referred to a
surgeon for RLQ pain and found that normal WBC and CRP had a negative
predictive value of 92.3% for the presence of appendicitis.11
• Yang, in 2006, retrospectively studied 897 patients who underwent
appendectomy (740 with appendicitis, 157 without) and found that only 6 of
740 patients with appendicitis had WBC <10,500 cells/mm3 AND neutrophilia
>75%, AND a normal CRP. This yields a sensitivity of 99.2% for the "triple
screen".12

Some studies have examined the sensitivity of combined WBC and CRP in the subpopulation of
patients older than 60 years.

• Gronroos, in 1999, studied 83 patients older than 60 years who underwent

appendectomy (73 found to have appendicitis) and found that no patient with
appendicitis had both normal WBC and CRP.13
• Yang et al, in 2005, retrospectively studied 77 patients older than 60 years
with histologically proven appendicitis and found that only 2 had a normal
"triple screen."14

Several studies have examined the accuracy of CRP and WBC in the subpopulation of pediatric
patients with suspected appendicitis.
 • Gronroos, in 2001, studied 100 children with pathology-proven appendicitis
and found that both WBC and CRP were normal in 7 of the 100 patients.15
• Mohammed, in 2004, prospectively studied 216 children admitted for
suspected appendicitis and found triple screen sensitivity and negative
predictive value of 86% and 81%, respectively.16
• Stefanutti et al, in 2007, prospectively studied more than 100 children
undergoing surgery for suspected appendicitis and found that either WBC or
CRP was elevated in 98% of those with pathology-proven appendicitis (CI,
95.3-100%).17

CRP is nonspecific and does not distinguish between various types of infection or inflammation.

Urinalysis

One study of 500 patients with acute appendicitis revealed that approximately one third reported
urinary symptoms, most commonly dysuria or right flank pain. One in 7 patients had pyuria
greater than 10 WBC per high power field, and 1 in 6 patients had greater than 3 RBC per high
power field. Thus, the diagnosis of appendicitis should not be dismissed due to the presence of
urologic symptoms or abnormal urinalysis.18

Imaging Studies

• Computed tomography
o Abdominal CT has become the most important imaging study in the
evaluation of patients with atypical presentations of appendicitis.
Studies have found a decrease in negative laparotomy rate and
appendiceal perforation rate when pelvic CT was used in selected
patients with suspected appendicitis.19,20,21,22
o

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

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

o Note that one study of asymptomatic volunteers undergoing pelvic CT

found that 42% had an "abnormal" appendiceal diameter of greater
than 6 mm and 78% of appendices did not fill after oral contrast. Thus,
findings on CT must be correlated with the clinical scenario.23
o Advantages of CT scanning include its superior sensitivity and accuracy
compared with those of other imaging techniques, ready availability,
noninvasiveness, and potential to reveal alternative diagnoses.
Disadvantages include radiation exposure, potential for anaphylactic
reaction if intravenous contrast agent is used, lengthy acquisition time
if oral contrast is used, and patient discomfort if rectal contrast is used.
o Initial studies evaluated sequential (nonhelical) CT in the diagnosis of
appendicitis. In 1993, Malone evaluated nonenhanced, sequential CT in
211 patients and reported a sensitivity of 87% and a specificity of
97%.24 The addition of intravenous and oral contrast agent increased
sensitivity to 96-98%. Thus, sequential CT with oral and intravenous
contrast enhancement 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 et al evaluated helical CT without contrast enhancement
and found a sensitivity of 90% and specificity of 97%.25 More recent
studies of noncontrast helical CT in adults with suspected appendicitis
showed a sensitivity of 91-96% and a specificity of 92-100%.26,27,28,29,30
o In a 2004 study of pediatric patients, Kaiser et al found that
nonenhanced CT was 66% sensitive.31 Sensitivity increased to 90% with
the use of intravenous contrast material. In a 2005 study of 112
pediatric patients, Hoecker and Bilman found that unenhanced CT
 achieved a sensitivity of 87.5%, specificity of 98.7%, positive predictive
value of 91.3%, and negative predictive value of 90.8%.32
o In 1997, Rao et al found that focused (lower abdominal and upper
pelvic) helical CT with 3% Gastrografin instilled into the colon (without
intravenous contrast agent) had a superior sensitivity of 98% and
specificity of 98%.33 Focused helical scanning without intravenous
contrast agent eliminates the risk of anaphylaxis and reduces the cost
to about $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 The literature suggests that limited helical CT with rectal contrast
enhancement is a highly accurate, time-efficient, cost-effective way to
evaluate adults with equivocal presentations for appendicitis. Two
studies of focused helical CT with rectal contrast in children suggest a
sensitivity of 95-97%. This is an excellent diagnostic approach in
patients with equivocal presentations who are poor candidates for
intravenous contrast.
o One recent retrospective study of 173 adults found that helical CT with
intravenous contrast only has a sensitivity of 100%, specificity of 97%,
positive predictive value of 97%, and negative predictive value of
100%.34 An earlier study of 78 patients with appendicitis found
sensitivity of 91.9%, specificity of 87.5%, and accuracy of 91%.35 In a
2005 retrospective review of 23 published reports, Anderson et al
found that CT without oral contrast was at least as accurate as CT with
oral contrast, achieving sensitivity of 95%, specificity of 97%, positive
predictive value of 97%, and negative predictive value of 96%.36
Elimination of oral contrast reduces emergency department length of
stay and delay to operative intervention.
o Continued improvements in helical CT technology may allow
nonenhanced helical CT to be the imaging test of choice for adults with
suspected appendicitis. Additional studies are needed to identify
subgroups that derive the most benefit from diagnostic imaging.
• Ultrasonography
o
 Sagittal graded compression transabdominal sonogram shows 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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Sagittal graded compression transabdominal sonogram shows 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.

o
Transverse graded compression transabdominal sonogram of an acutely
inflamed appendix. Note the targetlike appearance due to thickened wall and
surrounding loculated fluid collection.

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 Transverse graded compression transabdominal sonogram of an acutely
inflamed appendix. Note the targetlike appearance due to thickened wall and
surrounding loculated fluid collection.

o In 1986, Puylaert described a graded compression technique for

evaluating the appendix with transabdominal sonography.37 A 5-MHz
transducer is used. Gentle but firm pressure is applied on the RLQ to
displace intervening bowel gas and to decrease the distance between
the transducer and the appendix, improving image quality. An outer
diameter of greater than 6 mm, noncompressibility, lack of peristalsis,
or 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 sonography in women with low pelvic
tenderness if the appendix is not visualized on transabdominal scans.
o Numerous studies have documented a sensitivity of 85-90% and a
specificity of 92-96%. Five studies of graded compression
ultrasonography in children showed overall sensitivities of 85-95% and
specificities ranging from 47-96%. One study found sensitivity of 35%
and specificity of 98% in pediatric patients with perforated
appendicitis. The cost is approximately $225.
o Advantages of sonography include its noninvasiveness, short
acquisition time, lack of radiation exposure, and potential for diagnosis
of other causes of abdominal pain, particularly in the subset of women
of childbearing age. Many authorities believe that ultrasonography
should be the initial imaging test in pregnant women and in pediatric
patients because radiation exposure is particularly undesirable in these
groups.
o One new study suggests that ultrasonography should be incorporated
as a first-line imaging modality for the diagnosis of acute appendicitis
in adults.38
 In this study, 151 patients with suspected appendicitis
underwent the designed protocol. Graded-compression
ultrasonography was performed first. Patients with positive
results on graded-compression ultrasonography underwent
surgery. Those with inconclusive or negative results underwent
contrast-enhanced multidetector CT. Patients with positive
findings on CT also underwent surgery. Patients with negative
CT findings were admitted for observation. Positive
ultrasonography was confirmed at surgery in 71 of 79 patients,
and positive CT was confirmed in 21 patients. Thirty-nine
patients with normal CT results recovered and did not require
surgery. The sensitivity and specificity of this protocol was 100%
and 86%, respectively.
 Poortman et al concluded that this diagnostic pathway using
primary graded-compression ultrasonography and
complementary multidetector CT yields a high diagnostic
accuracy for acute appendicitis without adverse events from
delay in treatment. Although ultrasonography is less accurate
than CT, it can be used as a primary imaging modality and
avoids the disadvantages of CT. Observation is safe for patients
with negative findings on ultrasonography or CT.
o The principal disadvantage is that ultrasonography 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 sonogram of the RLQ 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 enhancement.
o Tzanakis and others proposed a clinical scoring system that assigns 6
points if appendiceal ultrasonogram is positive, 4 points for RLQ
 tenderness, 3 points for rebound tenderness, and 2 points for WBC
count greater than 12,000. In their prospective study of 303 adults
using a total score cut-off of 8 points or greater, they found sensitivity,
specificity, and accuracy of 95.4%, 97.4%, and 96.5%, respectively.39
These findings should be confirmed by additional studies before
routine clinical use.
• Abdominal radiography
o The kidneys-ureters-bladder (KUB) view is typically used. 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

Kidneys-ureters-bladder (KUB) radiograph shows an appendicolith in the

right lower quadrant. An appendicolith is seen in fewer than 10% of patients
with appendicitis, but, when present, it is essentially pathognomonic.

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 Kidneys-ureters-bladder (KUB) radiograph shows an appendicolith in the
right lower quadrant. An appendicolith is seen in fewer than 10% of patients
with appendicitis, but, when present, it is essentially pathognomonic.

o The consensus in the literature is that plain radiographs are

insensitive, nonspecific, and not cost-effective.
• Barium enema study
o A single-contrast study can be performed on an unprepared bowel.
Absent 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
study is in the range of 80-100%. However, as many as 16% of studies
in adults (22-39% in children) were technically unsuitable for
interpretation and excluded from data analysis.
o Advantages of barium enema study 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 results,
radiation exposure, insufficient sensitivity, and invasiveness. These
disadvantages make barium enema study a poor screening
examination for use by emergency departments.
o Barium enema study has essentially no role in the diagnosis of acute
appendicitis in the era of ultrasonography and CT.
• Radionuclide scanning
o Whole blood is withdrawn for radionuclide scanning. 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.
o

Technetium-99m radionuclide scan of the abdomen shows focal uptake of

labeled WBCs in the right lower quadrant consistent with acute appendicitis.

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Technetium-99m radionuclide scan of the abdomen shows focal uptake of

labeled WBCs in the right lower quadrant consistent with acute appendicitis.
 oFour early studies in adults with suspected appendicitis showed a
sensitivity of 80-90% and specificity of 92-100%.40,41,42,43 Two studies of
newer labeling techniques achieved sensitivities of 98% for the
presence of appendicitis.44,45
o Although 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 screening test for
appendicitis.
• Magnetic resonance imaging
o MRI plays a relatively limited role in the evaluation because of high
cost, long scan times, and limited availability, though the lack of
ionizing radiation makes it an attractive modality in pregnant patients.
o A single retrospective study assessed the accuracy of MRI in 51
pregnant patients with suspected appendicitis in whom
ultrasonography was nondiagnostic. Sensitivity, specificity, positive
and negative predictive values, and accuracy for MRI was 100%,
93.6%, 91.4%, 100%, and 94.0%, respectively.46
o Cobben et al showed that MRI is far superior to transabdominal
ultrasonography in evaluating pregnant patients with suspected
appendicitis.47
o When evaluating pregnant patients with suspected appendicitis,
graded compression ultrasound should be the imaging test of choice. If
ultrasonography demonstrates an inflamed appendix, the patient
should undergo appendectomy. If graded compression
ultrasonography is nondiagnostic, the patient should undergo MRI of
the abdomen and pelvis.

Other Tests

Clinical diagnostic scores

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.

The best known of these is the MANTRELS score, which tabulates migration of pain, anorexia,
nausea and/or vomiting, tenderness in the RLQ, rebound tenderness, elevated temperature,
leukocytosis, and shift to the left (Table 2).

Table 2. MANTRELS Score

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Table
Characteristic Scor
 e

M = Migration of pain to 1
the RLQ

A = Anorexia 1

N = Nausea and vomiting 1

T = Tenderness in RLQ 2

R = Rebound pain 1

E = Elevated temperature 1

L = Leukocytosis 2

S = Shift of WBC to the 1

left

Total 10

Scor
Characteristic
e

M = Migration of pain to 1
the RLQ

A = Anorexia 1

N = Nausea and vomiting 1

T = Tenderness in RLQ 2

R = Rebound pain 1

E = Elevated temperature 1

L = Leukocytosis 2

S = Shift of WBC to the 1

left

Total 10

Source.—Alvarado, 1986.48

Clinical scoring systems are attractive because of their simplicity; however, none has been
shown prospectively to improve on the clinician's 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.

McKay et al reviewed 150 emergency department patients who underwent abdominopelvic CT

to rule out appendicitis. In that series, patients with a MANTRELS score of 3 or lower had a
3.6% incidence of appendicitis, patients with scores of 4-6 had a 32% incidence of appendicitis,
and patients with scores of 7-10 had a 78% incidence of appendicitis. These investigators
suggested that patients with an Alvarado score of 0-3 could be discharged without imaging, that
those with scores of 7 or above receive surgical consultation, and those with scores of 4-6
undergo computed tomography.49

Schneider et al, in 2007, studied 588 patients aged 3-21 years and found that a MANTRELS
score of 7 or greater had a positive predictive value of 65% and a negative predictive value of
85%. They concluded that the MANTRELS score was not sufficiently accurate to be used as the
sole method for determining the need for appendectomy in the pediatric population.50

Computer-aided diagnosis

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

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

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

Computer-aided diagnosis is not widely available in US EDs.

Treatment
Emergency Department Care

• Treatment guidelines for patients with suspected acute appendicitis

o Establish intravenous access and administer aggressive crystalloid therapy to
patients with clinical signs of dehydration or septicemia.
o Patients with suspected appendicitis should not receive anything by mouth.
o Administer parenteral analgesic and antiemetic as needed for patient comfort. The
administration of analgesics to patients with acute undifferentiated abdominal
pain has historically been discouraged and criticized because of concerns that they
render the physical findings less reliable. At least 8 randomized controlled studies
now demonstrate that administering opioid analgesic medications to adult and
 pediatric patients with acute undifferentiated abdominal pain is safe; no study has
shown that analgesics adversely affect the accuracy of physical examination.
o Consider ectopic pregnancy in women of childbearing age, and obtain a
qualitative beta–human chorionic gonadotropin (beta-hCG) measurement in all
cases.
o Administer intravenous antibiotics to those with signs of septicemia and to those
who are to proceed to laparotomy.
• Nonsurgical treatment of appendicitis
o Anecdotal reports describe the success of intravenous antibiotics in treating acute
appendicitis in patients without access to surgical intervention (eg, submariners,
individuals on ships at sea).
o In one prospective study of 20 patients with sonography-proven appendicitis,
symptoms resolved in 95% of patients receiving antibiotics alone, but 37% of
these patients had recurrent appendicitis within 14 months.51
o Nonsurgical treatment may be useful when appendectomy is not accessible or
when it is temporarily a high-risk procedure.
• Preoperative antibiotics
o Preoperative antibiotics have demonstrated efficacy in decreasing postoperative
wound infection rates in numerous prospective controlled studies.
o Broad-spectrum gram-negative and anaerobic coverage is indicated.
o Preoperative antibiotics should be given in conjunction with the surgical
consultant.
o Penicillin-allergic patients should avoid beta-lactamase type antibiotics and
cephalosporins. Carbapenems are a good option in these patients.
o Pregnant patients should receive pregnancy category A or B antibiotics.

Consultations

• Consult a general surgeon.

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

Antibiotics

These agents are effective in decreasing the rate of postoperative wound infection and in
improving outcome in patients with appendiceal abscess or septicemia. The Surgical Infection
Society recommends starting prophylactic antibiotics before surgery, using appropriate spectrum
agents for less than 24 hours for nonperforated appendicitis and for less than 5 days for
perforated appendicitis. Regimens are of approximately equal efficacy, so consideration should
be given to features such as medication allergy, pregnancy category (if applicable), toxicity, and
cost.

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

Adult

7.5 mg/kg IV before surgery

Pediatric

15-30 mg/kg/d IV divided bid/tid for 7 d, or 40 mg/kg PO once; not to exceed 2 g/d

May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may

increase toxicity; disulfiram reaction may occur with orally ingested ethanol

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in hepatic disease; monitor for seizures and peripheral neuropathy

Gentamicin (Gentacidin, Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with agent against
gram-positive organisms and one against anaerobes. Not DOC. Consider if penicillins or other
less toxic drugs contraindicated, when clinically indicated, and in mixed infections caused by
susceptible staphylococci and gram-negative organisms. Numerous regimens; adjust dose for
CrCl and changes in volume of distribution. May be given IV/IM.

Adult

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

Pediatric

Infants/neonates: 7.5 mg/kg/d IV divided tid

Children: 6-7.5 mg/kg/d IV divided tid

Cefotetan (Cefotan)

Second-generation cephalosporin used as single-drug therapy for broad gram-negative and

anaerobic coverage. Half-life is 3.5 h. Give with cefoxitin to achieve effectiveness of single dose.

• Dosing
 • Interactions
• Contraindications
• Precautions

Adult

2 g IV once before surgery

Pediatric

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

• Dosing
• Interactions
• Contraindications
• Precautions

Consumption of alcohol within 72 h may produce disulfiramlike reactions; may increase

hypoprothrombinemic effects of anticoagulants; coadministration with potent diuretics (eg, loop
diuretics) or aminoglycosides may increase nephrotoxicity

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Reduce dose 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

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

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

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

Pediatric

<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

• Dosing
• Interactions
• Contraindications
• Precautions

Probenecid may increase effects; coadministration with aminoglycosides or furosemide may

increase nephrotoxicity (closely monitor renal function)

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged use or
repeated treatment; caution in patients with previously diagnosed colitis
Meropenem (Merrem)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Used as a
single agent, effective against most gram-positive and gram-negative bacteria.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

1 g IV q8h

Pediatric

40 mg/kg IV q8h

• Dosing
• Interactions
• Contraindications
• Precautions

Probenecid may inhibit renal excretion, increasing levels

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Pseudomembranous colitis and thrombocytopenia may occur (immediate discontinue)

Piperacillin and tazobactam sodium (Zosyn)

Drug combination of beta-lactamase inhibitor with piperacillin. Activity against some gram-
positive organisms, gram-negative organisms, and anaerobic bacteria. Used as a single agent,
inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active
multiplication.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

3.375 g IV q6h

Pediatric

300-400 mg piperacillin/kg/d IV divided q6-8h

• Dosing
• Interactions
• Contraindications
• Precautions

Tetracyclines may decrease effects of piperacillin; high concentrations of piperacillin may

physically inactivate aminoglycosides if administered in same IV line; effects when administered
concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels;
high dose parenteral penicillins may result in increased risk of bleeding

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; severe pneumonia, bacteremia, pericarditis, emphysema,

meningitis, and purulent or septic arthritis should not be treated with an oral penicillin during the
acute stage

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Perform CBCs prior to initiation of therapy and at least weekly during therapy; monitor for liver
function abnormalities by measuring AST and ALT during therapy; exercise caution in patients
diagnosed with hepatic insufficiencies; perform urinalysis, and BUN and creatinine
determinations during therapy and adjust dose if values become elevated; monitor blood levels to
avoid possible neurotoxic reactions

Ampicillin and sulbactam (Unasyn)

Drug combination of beta-lactamase inhibitor with ampicillin. Interferes with bacterial cell wall
synthesis during active replication, causing bactericidal activity against susceptible organisms.
Used as a single agent.
Activity against some gram-positive organisms, gram-negative organisms (nonpseudomonal
species), and anaerobic bacteria.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

1.5 (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6-8h; not to

exceed 4 g/d sulbactam or 8 g/d ampicillin

Pediatric

<3 months: Not established

3 months to 12 years: 100-200 mg ampicillin/kg/d (150-300 mg Unasyn) IV divided q6h
>12 years: Administer as in adults; not to exceed 4 g/d sulbactam or 8 g/d ampicillin

• Dosing
• Interactions
• Contraindications
• Precautions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and
has additive effects on ampicillin rash; may decrease effects of oral contraceptives
 • Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Analgesics

These agents can be used to relieve acute undifferentiated abdominal pain in patients presenting
to the ED.

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 to desired effect.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

Starting dose: 0.1 mg/kg IV/IM/SC

Maintenance dose: 5-20 mg/70 kg IV/IM/SC q4h
Relative hypovolemia: Start with 2 mg IV/IM/SC; reassess hemodynamic effects of dose

Pediatric

Infants and children: 0.1-0.2 mg/kg dose IV/IM/SC q2-4h prn; not to exceed 15 mg/dose; may
start at 0.05 mg/kg/dose
Follow-up
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. Recent experience
has also demonstrated that laparoscopic appendectomy is successful in
approximately 90% of cases of perforated appendicitis.
o Advantages of laparoscopic appendectomy include increased cosmetic
satisfaction and a decrease in the postoperative wound-infection rate. Some
studies show that laparoscopic appendectomy shortens the hospital stay and
convalescent period compared with open appendectomy.
o Disadvantages of laparoscopic appendectomy are increased cost and an operating
time approximately 20 minutes longer than that of open appendectomy. The latter
may resolve with increasing experience with laparoscopic technique.
o Laparoscopic appendectomy is contraindicated in patients with significant intra-
abdominal adhesions.
• Emergent versus urgent appendectomy
o One retrospective study suggests that the risk of appendiceal rupture is minimal in
patients with less than 24-36 hours of untreated symptoms.52 Another recent
retrospective study suggests that appendectomy within 12-24 hours of
presentation is not associated with an increase in hospital length of stay, operative
time, advanced stages of appendicitis, or complications compared to
appendectomy within 12 hours of presentation.53
o Additional studies are needed to demonstrate whether initiation of antibiotic
therapy followed by urgent appendectomy is as effective as emergent
appendectomy for patients with unperforated appendicitis.
• Immediate versus interval appendectomy for appendicitis with perforation
o Historically, immediate (emergent) appendectomy was recommended for all
patients with appendicitis, whether perforated or unperforated.
o Recent clinical experience suggests that patients with perforated appendicitis with
mild symptoms and localized abscess or phlegmon on abdominopelvic CT scans
can be initially treated with intravenous antibiotics and percutaneous or transrectal
drainage of any localized abscess. If the patient's symptoms, WBC count, and
fever satisfactorily resolve, therapy can be changed to oral antibiotics and the
patient can be discharged home. Delayed (interval) appendectomy can then be
performed 4-8 weeks later. This approach is successful in the vast majority of
patients with perforated appendicitis and localized symptoms. Some have
suggested that interval appendectomy is not necessary unless the patient presents
with recurrent symptoms. Further studies are needed to clarify whether routine
interval appendectomy is indicated.
o Further studies are necessary to identify the optimal treatment strategy in patients
with perforated appendicitis.
Complications

• Wound infection
• Dehiscence
• Bowel obstruction
• Abdominal/pelvic abscess
• Stump appendicitis - Although rare, approximately 36 reported cases of appendicitis in
the surgical stump after prior appendectomy exist.54
• Death (rare)

Prognosis

• The prognosis is 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
Medicolegal Pitfalls

• For approximately 10% of adults with appendicitis, the condition is not diagnosed
correctly on their first visit to the health care provider.
• 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

• Pregnant women
o The incidence of appendicitis is unchanged in pregnancy, but the clinical
presentation is more variable than at other times.
o During pregnancy, the appendix migrates in a counterclockwise direction toward
the right kidney, rising above the iliac crest at about 4.5 months' gestation.
o 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 considered a
possible sign of appendiceal inflammation.
o 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 than at other times, and no reliable distinguishing WBC parameters
are cited in the literature.
 o One study of 22 pregnant women in the first and second trimesters showed that
graded compression ultrasonography had a sensitivity of 66% and specificity of
95%.55
o Diagnostic laparoscopy has also been suggested for pregnant patients in the first
trimester with suspected appendicitis.
o Although negative appendectomy does not appear to adversely affect maternal or
fetal health, 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 Appendicitis is misdiagnosed in 33% of nonpregnant women of childbearing age.
The most frequent misdiagnoses are PID, followed by gastroenteritis and urinary
tract infection.
o In distinguishing appendiceal pain from that of PID, anorexia and onset of pain
more than 14 days after menses suggests appendicitis. Previous PID, vaginal
discharge, or urinary symptoms indicates PID.
o On physical examination, tenderness outside the RLQ, cervical motion
tenderness, vaginal discharge, and positive urinalysis support the diagnosis of
PID.
• Children
o Appendicitis is misdiagnosed in 25-30% of children, 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 Children with misdiagnosed appendicitis are more likely than their 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 children with a misdiagnosis
than in others include bowel sounds; peritoneal signs; rectal findings; and ear,
nose, and throat findings.
• Elderly patients
o Appendicitis in patients older than 60 years accounts for 10% of all
appendectomies.
o The incidence of misdiagnosis is increased in elderly patients.
o In patients with comorbid conditions, diagnostic delay is correlated with increased
morbidity and mortality.
o Older patients tend to seek medical attention later in the course of illness;
therefore, a duration of symptoms in excess of 24-48 hours should not dissuade
the clinician from the diagnosis.
• Multimedia
 Media file 1: CT scan reveals an enlarged appendix with
thickened walls, which do not fill with colonic contrast agent,
lying adjacent to the right psoas muscle.

(Enlarge Image)
• [ CLOSE WINDOW ]

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

Media file 2: Sagittal graded compression transabdominal sonogram shows 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.

(Enlarge Image)
• [ CLOSE WINDOW ]
•
• Sagittal graded compression transabdominal sonogram shows 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.
 Media file 3: Transverse graded compression transabdominal sonogram
of an acutely inflamed appendix. Note the targetlike appearance due to
thickened wall and surrounding loculated fluid collection.

(Enlarge Image)
• [ CLOSE WINDOW ]

•
 • Transverse graded compression transabdominal sonogram of an acutely inflamed
appendix. Note the targetlike appearance due to thickened wall and surrounding
loculated fluid collection.

Media file 4: Kidneys-ureters-bladder (KUB) radiograph shows an

appendicolith in the right lower quadrant. An appendicolith is seen in
fewer than 10% of patients with appendicitis, but, when present, it is
essentially pathognomonic.

(Enlarge Image)
• [ CLOSE WINDOW ]

•
• Kidneys-ureters-bladder (KUB) radiograph shows an appendicolith in the right
lower quadrant. An appendicolith is seen in fewer than 10% of patients with
appendicitis, but, when present, it is essentially pathognomonic.
 Media file 5: Technetium-99m radionuclide scan of the abdomen
shows focal uptake of labeled WBCs in the right lower quadrant
consistent with acute appendicitis.

(Enlarge Image)