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EVIDENCE-BASED DIAGNOSTICS

Diagnostic Accuracy of History, Physical


Examination, Laboratory Tests, and Point-
of-care Ultrasound for Pediatric Acute
Appendicitis in the Emergency Department:
A Systematic Review and Meta-analysis
Roshanak Benabbas MD, Mark Hanna MD, Jay Shah, and Richard Sinert DO

ABSTRACT
Background: Acute appendicitis (AA) is the most common surgical emergency in children. Accurate and timely
diagnosis is crucial but challenging due to atypical presentations and the inherent difficulty of obtaining a reliable
history and physical examination in younger children.

Objectives: The aim of this study was to determine the utility of history, physical examination, laboratory tests,
Pediatric Appendicitis Score (PAS) and Emergency Department Point-of-Care Ultrasound (ED-POCUS) in the
diagnosis of AA in ED pediatric patients. We performed a systematic review and meta-analysis and used a test–
treatment threshold model to identify diagnostic findings that could rule in/out AA and obviate the need for further
imaging studies, specifically computed tomography (CT) scan, magnetic resonance imaging (MRI), and radiology
department ultrasound (RUS).

Methods: We searched PubMed, EMBASE, and SCOPUS up to October 2016 for studies on ED pediatric
patients with abdominal pain. Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) was used to
evaluate the quality and applicability of included studies. Positive and negative likelihood ratios (LR+ and LR–) for
diagnostic modalities were calculated and when appropriate data was pooled using Meta-DiSc. Based on the
available literature on the test characteristics of different imaging modalities and applying the Pauker-Kassirer
method we developed a test–treatment threshold model.

Results: Twenty-one studies were included encompassing 8,605 patients with weighted AA prevalence of
39.2%. Studies had variable quality using the QUADAS-2 tool with most studies at high risk of partial
verification bias. We divided studies based on their inclusion criteria into two groups of “undifferentiated
abdominal pain” and abdominal pain “suspected of AA.” In patients with undifferentiated abdominal pain,
history of “pain migration to right lower quadrant (RLQ)” (LR+ = 4.81, 95% confidence interval [CI] = 3.59–6.44)
and presence of “cough/hop pain” in the physical examination (LR+ = 7.64, 95% CI = 5.94–9.83) were most
strongly associated with AA. In patients suspected of AA none of the history or laboratory findings were
strongly associated with AA. Rovsing’s sign was the physical examination finding most strongly associated with
AA (LR+ = 3.52, 95% CI = 2.65–4.68). Among different PAS cutoff points, PAS ≥ 9 (LR+ = 5.26, 95% CI =
3.34–8.29) was most associated with AA. None of the history, physical examination, laboratory tests findings,

From the Department of Emergency Medicine (RB, RS) and the Department of Pediatrics (MH), State University of New York/SUNY Downstate
Medical Center, Brooklyn, NY; and the Department of Emergency Medicine (RB, JS, RS) and the Department of Pediatrics (MH), Kings County
Hospital Center, Brooklyn, NY.
Received November 13, 2016; revision received January 17, 2017; accepted February 6, 2017.
The authors have no relevant financial information or potential conflicts to disclose.Supervising Editor: Elizabeth Alpern, MD, MSCI.
Address for correspondence and reprints: Richard Sinert, DO; e-mail: nephron1@gmail.com.
ACADEMIC EMERGENCY MEDICINE 2017;24:523–551.

© 2017 by the Society for Academic Emergency Medicine ISSN 1069-6563


doi: 10.1111/acem.13181 PII ISSN 1069-6563583 523
524 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

or PAS alone could rule in or rule out AA in patients with undifferentiated abdominal pain or those suspected
of AA. ED-POCUS had LR+ of 9.24 (95% CI = 6.24–13.28) and LR– of 0.17 (95% CI = 0.09–0.30). Using our
test–treatment threshold model, positive ED-POCUS could rule in AA without the use of CT and MRI, but
negative ED-POCUS could not rule out AA.

Conclusion: Presence of AA is more likely in patients with undifferentiated abdominal pain migrating to the RLQ
or when cough/hop pain is present in the physical examination. Once AA is suspected, no single history, physical
examination, laboratory finding, or score attained on PAS can eliminate the need for imaging studies. Operating
characteristics of ED-POCUS are similar to those reported for RUS in literature for diagnosis of AA. In ED patients
suspected of AA, a positive ED-POCUS is diagnostic and obviates the need for CT or MRI while negative ED-
POCUS is not enough to rule out AA.

A bdominal pain is one of the most common chief


complaints among emergency department (ED)
pediatric patients with over 800,000 annual visits in
serial examination or further workup. In patients
with medium-risk PAS (PAS = 4–6), Bachur et al.23
suggested appendectomy in those with positive US
patients younger than 15 years old.1 Although many and observation in those with negative or equivocal
cases are benign, it is crucial to correctly and timely US. However, this single-center study used radiology
identify those requiring further workup, imaging stud- department US (RUS) as opposed to ED point-of-
ies, or surgical intervention. Acute appendicitis (AA) is care US (ED-POCUS)
the most common surgical emergency in children with Not all EDs have a radiology department sonogra-
72,000 hospital discharges per year.2 Diagnosing AA pher available 24/7, which can delay the diagnosis of
in children remains challenging due to atypical presen- AA and increase the risk of complications. ED-
tations3–5 and difficulty of obtaining a reliable history POCUS of the appendix can provide valuable, real-
and physical examination, especially in younger chil- time information to the treating physician while
dren.6,7 Prompt diagnosis of AA can prevent complica- decreasing ED length of stay.24,25
tions such as perforation and abscess formation.8–11 We decided to use a systematic review and meta-
In everyday clinical practice, physicians combine analysis methodology to evaluate which element(s) of
their clinical suspicion of AA with laboratory tests history, physical examination, laboratory tests, PAS, or
findings and imaging studies to make a final diagno- ED-POCUS are most useful in the diagnosis of AA in
sis. AA scoring systems such as Pediatric Appendici- ED pediatric patients. Specifically, we were interested
tis Score (PAS)12 and Alvarado Score13 use elements in investigating if any of these findings could obviate
of history, physical examination, and laboratory test the need for radiology department resources (CT, mag-
findings to identify patients with a high risk of hav- netic resonance imaging [MRI], or RUS) and, there-
ing AA. However, the reported sensitivity and speci- fore, expedite patient disposition.
ficity of these scoring systems vary widely between Prior systematic reviews of pediatric appendicitis by
studies14–17 and neither scoring system (PAS12 and Bundy et al.6 and Dahabreh et al.26 included studies
Alvarado13) integrates imaging studies despite the that were heterogeneous in design and study popula-
increasing use of computed tomography (CT) scan, tion. However, to evaluate the operating characteristics
in the ED.18–20 of index tests in ED patients, it is more useful to
Given the concern of exposing children to ionizing examine studies limited to the ED population. There-
radiation by using CT scan, the American College of fore, we limited our population to pediatric patients
Emergency Physician21 and American College of Radi- presenting to the ED with abdominal pain. We also
ology22 recommend considering ultrasonography (US) limited our assessment of US to ED-POCUS, per-
as the initial radiologic modality for pediatric AA. formed and interpreted by ED physicians.
In an attempt to integrate imaging and clinical
and laboratory findings, Bachur et al.23 calculated
METHODS
PAS in a cohort of ED pediatric patients suspected
of AA who had undergone US study. Bachur et al.23
Study Design
suggested in their conclusion that patients with high-
risk PAS (PAS = 7–10) but negative US, or low-risk We conducted a systematic review and meta-analysis of
PAS (PAS = 0–3) but positive US, benefit from studies on the diagnosis of AA in ED pediatric
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 525

patients with abdominal pain. The design of this sys- A meeting was held and any disagreements in study
tematic review and meta-analysis follows the recom- selection were resolved by consensus before a final list
mendations of the Preferred Reporting Items for of included studies was made. A reference list of
Systematic Review and Meta-analyses (PRISMA)27 included studies was reviewed to seek additional stud-
guideline and Meta-analysis of Observational Studies ies that could be included.
in Epidemiology (MOOSE) statement.28
Data Analysis
Search Strategy Sensitivities, specificities, and likelihood ratios (LRs)
In conjunction with a medical librarian, we searched were calculated based on construction of two-by-two
the medical literature in PubMed, EMBASE, and tables for findings of each included study. When more
SCOPUS from their inception up to October 2016 than one study reported a variable, we pooled the data
for search terms diagnosis and appendicitis. See Data using Meta-DiSc software with random-effects model.29
Supplement S1 [available as supporting information in Inter-study heterogeneity was assessed using the
the online version of record of this paper, which is DerSimonian-Laird random-effect model. We pooled
available at http://onlinelibrary.wiley.com/doi/10. data only when I-square was less than 50% and
1111/acem.13181/full] for search strategies and MeSH reported point estimates for variables demonstrating
terms used. The PubMed, EMBASE, and SCOPUS high heterogeneity.
searches were combined and limited to human sub-
jects and English language for three separate search Quality Assessment
topics: history and physical examination, laboratory Two authors (RB, MH) independently assessed the
tests, and ED-POCUS. Narrative reviews, case-control quality and applicability of each included study
studies, and case reports were excluded. using the Quality Assessment Tool for Diagnostic
Accuracy Studies (QUADAS-2).30 Agreement
Study Selection and Data Abstraction between the two reviewers was assessed by calculat-
Two authors (RB, MH) independently selected articles ing kappa using SPSS (IBM SPSS, Version 21,
for each index test category (history and physical exami- IBM Corp.)
nation, laboratory tests, and ED-POCUS) from the Four domains were assessed for biases: 1) patient
combined PubMed, EMBASE, and SCOPUS search selection, 2) index test, 3) reference test, and 4) flow
for the full-text review. Each reviewer independently and timing. Several considerations were established
selected potentially eligible studies. Studies eligible for prior to assessing the quality of individual studies, and
inclusion were those that described patients with the a set of signaling questions was developed for each sec-
maximum age of 21 years presenting to the ED with tion of the QUADAS-2.
either “undifferentiated abdominal pain” or abdominal The ideal study population would be patients who
pain “suspected of AA.” In studies with both adult presented to the ED with abdominal pain and subse-
and pediatric participants, we included only those that quently received both index test and reference test
either presented the data from their pediatric partici- with the interpreter of each test blinded to the results
pants separately or could provide us with that data of the other. An exclusion based on previous history
upon contacting the author. Studies on ED-POCUS of abdominal surgeries other than appendectomy,
were included only if performed and interpreted by an abdominal trauma, or previous workup such as surgi-
ED physician. Studies were included only if provided cal consultation, imaging studies, or laboratory tests
sufficient data to construct two-by-two tables either in were judged to be inappropriate.
the text or after contacting the author. Included studies If the execution of the index test was not clearly
were those which described positive and negative index defined or the index test was performed after knowing
test along with the final diagnosis using a criterion the result of the reference test, that portion of QUA-
standard, histopathologic diagnosis of AA. Among tri- DAS-2 would be at high risk for bias. For laboratory
als on clinical scores, we decided to include only those tests and ED-POCUS the criteria for a positive test
dedicated to PAS, as the most broadly studied clinical needed to be clearly specified for that study to be at
score for the diagnosis of AA in children. We decided low risk of bias. For physical examination, the deci-
not to review Alvarado score as it was originally devel- sion to qualify a finding as positive or negative was left
oped for identifying adult patients at high risk of AA. at physician’s discretion. We assessed the index-
526 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

EMBASE search H&P EMBASE search Labs EMBASE search US


(n=499) (n=155) (n=575)
PUBMED search H&P PUBMED search Labs PUBMED search US
(n=196) (n=172) (n=454)
SCOPUS search H&P SCOPUS search Labs SCOPUS search US
(n=151) (n=158) (n=557)
Manual search H&P Manual search Labs Manual search US
Identification

(n=2) (n=1) (n=1)

Duplicates removed (n=750)

Arcles aer duplicates removed


Screening

n= 2,171
(H&P: 713- Labs: 378-ED-POCUS: 1,080)

Arcles excluded by tle or abstract


(n=2,085)

Full-text arcles excluded:


Full-text reviewed
Eligibility

(n=86)
-Retrospecve Design (n=37)

-Missing Data for 2x2 Tables (n=3)

-Including only pre-op or post


appendectomy or admied paents
(n=11)

-Not ED seng (n=7)


Included

-Referral paents (n=4)

Arcles included -Overlapping data with another study


(n=21) (n=3)

Figure 1. Study selection process. H&P = history and physical examination; ED-POCUS: Emergency Department Point-of-Care Ultrasound.
[Color figure can be viewed at wileyonlinelibrary.com]

reference test interval as appropriate if patients tests were conducted in a manner that differed from
received the index test upon presentation to the ED routine clinical practice.
and were sent to the operating room in a timely man-
ner if indicated. If performance of the reference test Test–Treatment Threshold Estimates
was not clearly defined or the interpreter of the refer- We used the Pauker-Kassirer method31 to assess the
ence test was not blinded to the result of the index testing and treatment thresholds for CT scan and
test, that portion of QUADAS-2 would be at risk of MRI and investigated which element(s) of history and
bias. Concerns regarding the applicability of the physical examination, laboratory tests, PAS, or ED-
results of index or reference test were raised if these POCUS could have sufficient discriminatory power to
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 527

eliminate the need for CT scan, MRI, or RUS in the Prevalence


diagnosis of AA and facilitate patient disposition. The combined population from the 21 studies included
We used the accuracy and risk associated with each in this review was 8,605 patients of whom 3,344 were
diagnostic modality as well as the risk and benefit of diagnosed with AA (38.86%, 95% confidence interval
treatment to estimate thresholds for testing and treat- [CI] = 37.80–39.89). Prevalence of AA ranged from
ment for each imaging modality (CT, MRI, and RUS). 9.8%109 to 63%108 with weighted prevalence of 39.2%
Using the operating characteristics of each index test (95% CI = 38.2–40.3). The inclusion criteria were not
(history, physical examination, laboratory finding, PAS, uniform across studies. Therefore, we decided to group
and ED-POCUS) we then estimated the posttest prob- studies based on their inclusion criteria.
ability of AA applying the Bayes theorem. Posttest The weighted prevalence of AA was significantly
probabilities of AA were then compared to the testing (p < 0.001) higher in studies that used either “abdom-
and treatment thresholds of CT, MRI, and RUS to inal pain suspected of AA” or “right lower quadrant
investigate if presence or absence of each index test (RLQ) pain” as their inclusion criteria (19 stud-
can rule in or rule out AA without the use of radiol- ies,15,16,23–25,94,101–108,110–114 n = 7,510, AA preva-
ogy department resources. lence = 42.8%, 95% CI = 41.7–43.9) compared to
those that used “abdominal pain” or undifferentiated
abdominal pain (two studies,14,109 n = 1,095, AA
RESULTS
prevalence = 13.4%, 95% CI = 11.5–15.6).
The PubMed, EMBASE, and SCOPUS searches identi-
fied 846 citations for history and physical examination, History and Physical Examination
485 citations for laboratory studies, and 1,586 citations Fifteen studies provided data on history and physical
for ED-POCUS. Upon review of the bibliography of examination findings (Table 1). All except for
the reviewed articles, four more citations were found. two104,114 were single-center studies. Inclusion criteria
We decided to exclude retrospective studies32–68 were not uniform across reviewed studies. Goldman
from our review. All of these studies had issues related et al.14 and O’Shea et al.109 used undifferentiated
to reliability of their retrospectively abstracted data. All abdominal pain as inclusion criteria while 11 trials
of the retrospective studies failed to document meth- included patients with suspected of AA and two (Wu
ods suggested by Gilbert et al.69 to improve their accu- et al.108 and Khan et al.112) used RLQ pain. Sample
racy and minimize inconsistencies in data acquisition. size varied considerably between studies ranging from
If an article did not provide adequate data to repro- 40 (Doniger and Kornblith110) to 2,133 (Bachur
duce two-by-two tables it was excluded from the et al.114). While some studies excluded patients with
review.70–72 We also excluded any article that did not history of abdominal surgery at any time23,94,113,114,130
mention “emergency department,” “ED,” or “emer- or in the previous year,101 others14,15,104,105 only
gency room” as their study setting12,73–78 or trials that excluded patients with history of appendectomy. All
included pre- or post-appendectomy,79–86 admitted,87–89 included studies defined AA as positive histopatho-
or referral patients.90–93 We found four articles with logic findings in patients who underwent appendec-
possibility of having overlapping patient population: tomy and follow-up by phone call in nonsurgical
Schneider et al.,94 Becker et al.,3 Colvin et al.,49 and patients. The follow-up length ranged from 5 days
Kharbanda et al.95 We decided to include only Schnei- (Cayrol et al.105) to 6 months (Sivitz et al.25). Zuniga
der et al.94 and exclude the other three. Our decision et al.15 used a database search for nonsurgical patients
was based on the fact that Schneider et al.,94 unlike and in Huckins et al.,104 discharge diagnosis was con-
other three, provided data on PAS. Trials on the accu- sidered as the final diagnosis.
racy of clinical scores, other than PAS, were only We decided to report the pooled data only when I-
included if they reported the test characteristics of all of square was less than 50% and only report point esti-
their variables. Articles that only provided the final score mates for variables that showed moderate to high
with limited or no data on the variables were heterogeneity.115 In Tables 3–5, I-square is mentioned
excluded.96–100 Twenty-one studies14–16,23–25,94,101–114 when pooling of the data was not possible due to high
were included in our review. The study selection process heterogeneity (I2 > 50%).
is shown in Figure 1. Tables 1 and 2 describe the char- Across studies on patients suspected of AA
acteristics of included studies. (Table 3), none of the history findings had strong test
528 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

Table 1
Description of Reviewed Studies: History, Physical Exam and Lab findings

Potential Predictors Prevalence


Study Participants of Appendicitis Gold Standard (95% CI)
O’Shea, 1988 Inclusion: Anorexia • Histopathology 9.8% (7-14)
• Abdominal Pain < 1 week Nausea/Vomiting • No surgery, F/u* 3-6 D
• Age: 3-18 years Fever
Exclusion: Diarrhea
• Recent trauma Dysuria
• Recurrent abdominal pain Lethargy
• Care taker not knowing
English
Sample Size: 246
Median Age: 11 years
Gender: 48% M
Schneider, 2007 Inclusion: Anorexia • Histopathology 34% (30-37)
• Suspected appendicitis Nausea/Vomiting • No surgery, F/u 2 W or
• Age: 3-21 year Pain migration to RLQ contacting
Exclusion: RLQ tenderness patient’s pediatrician
• Pregnancy Cough/hop pain
• Previous abdominal surgery Rebound tenderness
• Chronic medical conditions T≥37.3
WBC≥10,000
• Abdominal imaging in Neutrophil≥75%
< 2 weeks
Sample Size: 588
Median Age: 11.9 years
Gender: 54% M
Goldman,2008 Inclusion: Anorexia • Histopathology 14.5% (12-17%)
• Abdominal pain < 1 week Nausea/Vomiting • No surgery, F/u
• Age:1-17 years Pain migration to RLQ 5-7 days
Exclusion: Cough/hop pain
• Previous appendectomy Fever (T≥38° C)
RLQ tenderness
Sample Size: 849
Mean Age: NS WBC≥10,000
Gender: NS Neutrophil ≥ 7500
Kwan, 2010 Inclusion: RLQ Tenderness • Histopathology 55% (48-61%)
• Suspected appendicitis RLQ Rebound tenderness • No surgery, F/u
• Age:1-18 years LLQ Tenderness 2-6 weeks
Exclusion: Periumbilical Tenderness
• Pregnancy RUQ Tenderness
• Chronic medical conditions LUQ Tenderness
• Abdominal surgery in < 1 year Epigastric Tenderness
Suprapubic Tenderness
Sample Size: 209
WBC≥12,000
Mean Age: 10.5  3.7 years
CRP≥3 mg/dL
Gender: 59% M
Mandeville,2011 Inclusion: Anorexia • Histopathology 54% (48-59%)
• Suspected appendicitis Nausea/Vomiting • No surgery, F/u
• Age: 4-17 years Pain Migration to RLQ 2 weeks
Exclusion: RLQ tenderness
• Pregnancy T≥37.3
• Previous abdominal surgery Rebound tenderness
• Chronic medical conditions Cough/hop pain
WBC≥10,000
• Abdominal imaging in Neutrophil≥75%
< 2 weeks
Sample Size: 287
Mean Age: 9.8 3.1 years
Gender: 52.6% M
Escriba, 2011 Inclusion: PAS • Histopathology 42% (33-52%)
• Suspected appendicitis • No surgery, F/u
• Age: 4-18 years 10 days
Exclusion:
• Lab tests not available
Sample Size: 99
Mean Age: 11.2  3.7 years
Gender: 62.6% M

(Continued)
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Table 1 (continued)

Potential Predictors Prevalence


Study Participants of Appendicitis Gold Standard (95% CI)
Wu, 2012 Inclusion: PAS • Histopathology 63% (60-65%)
• RLQ pain • No surgery, F/u
• Age: 3-18 years 2 weeks
Exclusion:
• Pain duration ≥3 days
• Loss to F/u
Sample Size: 1,395
Mean Age: 11.1 4.2 years
Gender: 46.2% M
Khan, 2012 Inclusion: Anorexia • Histopathology 44% (30-58)
• RLQ pain Nausea/Vomiting • No surgery, F/u
• Age: 5-17 years Fever 24 hours and
Exclusion: RLQ Pain at 2 weeks
• Obvious signs of LLQ Pain
Epigastric Pain
Gastroenteritis
• Chronic medical conditions RLQ Tenderness
RLQ Rebound
• Pregnancy tenderness
Sample Size: 50
Guarding
Mean Age: 113.2 years Bowel Sounds
Gender:44% M Procalcitonin
Santillanes, 2012 Inclusion: Fever • Histopathology 41% (36-45%)
• Suspected appendicitis Nausea/Vomiting • No surgery, F/u
Exclusion: NS Anorexia 1 week
Sample Size: 475 RLQ pain
Mean Age: 11 years Periumbilical pain
Gender: 50% M Obstipation
Diarrhea
RLQ tenderness
RLQ Rebound
tenderness
Guarding
Psoas Sign
Obturator sign
Rosving’s sign
WBC≥10,000
Kentsis,2012 Inclusion: Nausea/Vomiting • Histopathology 49% (35-62%)
• Suspected Appendicitis Fever • No surgery, F/u
• Age <18 years Pain Migration to RLQ 6-8 weeks
• Surgical consult or Pain Duration
RLQ Pain or Tenderness
Imaging requested
Exclusion:
• Chronic Medical Conditions
• Pregnancy
Sample Size:49
Mean Age: 10.9  4.3 years
Gender: 53% M
Zuniga, 2012 Inclusion: Anorexia • Histopathology 28% (20-37%)
• Suspected Appendicitis Nausea/Vomiting • No surgery, F/u 7 days
• Age< 14 years Pain Migration to RLQ through database search
Exclusion: T≥37.3
• Pain ≥7 days RLQ Tenderness
• Previous appendectomy Rebound Tenderness
• Lab tests not available Cough/Hop Pain
WBC≥ 10,000
Sample size: 101
Neutrophil ≥ 7500
Mean age: 9.51  2.76 years
Gender: 54.5% M
Huckins, 2013 Inclusion: Anorexia • Histopathology 29% (25-32%)
• Suspected appendicitis Nausea/Vomiting • No surgery, Discharge
• Age:2-20 years Pain migration to RLQ diagnosis, No F/u
• Pain< 72 hours RLQ tenderness
Fever ≥ 37.5°C
Exclusion:
• Previous appendectomy Rebound tenderness
• Chronic Medical condition Rigidity and guarding
Rovsing’s sign
• Abdominal trauma
• Invasive abdominal procedures
• Participation in any other
research
protocol in the past 2 W
Sample Size: 503
Median Age: 12 years
Gender: 43% M

(Continued)
530 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

Table 1 (continued)

Potential Predictors Prevalence


Study Participants of Appendicitis Gold Standard (95% CI)
Sivitz, 2014 Inclusion: Anorexia • Histopathology 33% (27-39)
• Suspected appendicitis Nausea/Vomiting • No surgery, F/u,6
Exclusion: Pain migration to RLQ months
• Previous abdominal surgery Fever
• Unstable Vital Signs Rebound Tenderness
Cough/Hop pain
Sample Size: 231
Median Age: 10 years WBC≥10,000
Gender: 60% M Neutrophil≥ 6750
Urine Ketones
Bachur,2015 Inclusion: Anorexia • Histopathology 29% (26-32%)
• Suspected appendicitis Nausea • No surgery, F/u
• Age: 3-18 years Pain migration to RLQ 1-2 week(s)
• Having RLQ Ultrasound T≥38
Maximal pain in RLQ
Exclusion:
• Previous abdominal surgery Guarding
• Current Antibiotic use Rebound
Cough/Hop Pain
• Chronic medical condition RLQ
Sample Size: 728
Pain duration
Median Age: 11.7 years WBC≥10,000
Gender: 44% M Neutrophil ≥75%
Cayrol,2016 Inclusion: Nausea and Vomiting • Histopathology 38% (30-47%)
• Suspected appendicitis T≥37.5 • No surgery, F/u
• Age: 1-16 years Pain Migration to RLQ 5 days
Having lab tests RLQ pain
Exclusion: Diffuse Abdominal Tenderness
• Previous appendectomy Rebound Tenderness
• Chronic medical conditions WBC≥10,000
• Pregnancy D-dimer
CRP
• Anticoagulant treatment
Sample Size: 135
Mean Age: 9.44  3.3 years
Gender: 51.1%
Bachur, 2016 Inclusion: Symptom Duration • Histopathology 41% (39-43)
• Suspected appendicitis WBC • No surgery, F/u
• Age: 3-18 years ANC 1-2 week(s), Medical
• Pain< 72 hours record review for
• WBC and ANC requested in 3 months
workup
Exclusion:
• Previous abdominal surgery
• Pregnancy
• Chronic GI conditions
Sample Size: 2,133
Median Age: 10.9 years
Gender: 42% M
Khanfer, 2016 Inclusion: PAS • Histopathology 30.6% (24-37%)
• Suspected appendicitis • No surgery, F/u
• Age: 5-17 years 1 months
Exclusion:
• Previous appendectomy
• Previous Abdominal Surgery
• Established diagnosis of AA
• Pregnancy
Sample Size: 180
Mean Age: 11.2  3.1 years
Gender: 43.3% M
Doniger, 2016 Inclusion: Anorexia • Histopathology 40% (26-55)
• Suspected appendicitis Nausea/Vomiting • No surgery, F/u
• Age 2-18 years Fever >2 weeks
Exclusion: RLQ Rebound
• Pregnancy Tenderness
• Previous abdominal imaging
Sample Size: 40
Mean Age: 9.26 years
Gender: 50% male

*F/u = Follow-up in patients who were treated nonsurgically. Follow-up was done via telephone unless otherwise specified.
CRP = C-reactive protein; LLQ = left lower quadrant; M = male; NS = not specified; PAS = Pediatric Appendicitis Score; RLQ = right
lower quadrant, T = temperature; WBC = white blood cells.
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 531

characteristics with “pain migration to RLQ” demon- Across studies on patients suspected of AA, most
strating the highest LR+ (1.75, 95% CI = 1.58–1.94) laboratory tests had poor test characteristics (Table 7).
and “anorexia” having the lowest LR– (0.58, 95% Of laboratory tests reported in more than one article,
CI = 0.52–0.65). In patients with undifferentiated CRP > 3 was most suggestive of AA (LR+ = 2.10,
abdominal pain (Table 4) and based on the results 95% CI = 1.61–2.76) while WBC count < 10,000
from a single study (O’Shea et al.109) fever was most was most associated with absence of AA (LR– = 0.21,
suggestive of AA, LR+ 3.4 (95% CI = 2.42–4.76) 95% CI = 0.19–0.25). A combination of WBC count
while absence of fever decreased the probability of AA ≥ 12,000 and CRP > 3 had the highest LR+ (4.36,
the most (LR– = 0.32, 95% CI = 0.16–0.64). 95% CI = 2.26–8.42); however, this combination was
Among studies on patients suspected of AA only described in one101 study (Table 7).
(Table 5), Rovsing’s sign was the physical examination One study, by Bachur et al.,114 on patients with “sus-
finding most suggestive of AA (LR+ = 3.52, 95% pected AA” investigating the effect of age on WBC
CI = 2.65–4.68) while its absence had a minimal count and ANC in AA patients found these variables
effect on probability of AA (LR– = 0.72, 95% CI = to have a better diagnostic performance in older chil-
0.66–0.78). Presence or absence of fever in physical dren. Across reported cutoff points of WBC count
examination (as measured in the ED) did not signifi- (≥5,000 to ≥15,000) LR+ was 1.05 to 1.91 in children
cantly alter the probability of AA (LR+ = 1.13 and younger than 5 years versus LR+ of 1.05 to 5.25 in chil-
LR– = 0.94). Grouping studies based on cutoff point dren older than 12 years. Similarly, across different cut-
used to define fever did not improve the test character- off points of ANC (≥5,000 to ≥15,000), LR+ was 1.25
istics of this variable (Table 6). Only one study (Gold- to 1.87 in children younger than 5 years versus 1.7 to
man et al.14) investigated physical examination 5.85 in children older than 12 years.
findings in patients with undifferentiated abdominal Only one study (Goldman et al.14) reported labora-
pain (Table 4). In Goldman et al.14 study “cough/hop tory tests in patients with undifferentiated abdominal
pain” (LR+ = 7.64, 95% CI = 5.94–9.83) and “right pain (Table 4). In the study by Goldman et al.,14
iliac fossa tenderness” (LR+ = 4.74, 95% CI = 3.94– ANC ≥ 7,500 was most associated with diagnosis of
5.70) were most suggestive of AA. AA (LR+ = 2.33, 95% CI = 1.89–2.88) while
absence of leukocytosis was most associated with
Laboratory Tests absence of AA (LR– 0.22, 95% CI = 0.13–0.36).
Eleven studies provided data on laboratory tests: Ten
studies15,23,94,101,103–105,111,112,114 were done on patients PAS
suspected of AA and one study14 on patients with undif- Seven studies evaluated PAS at different cutoff points.
ferentiated abdominal pain (Table 1). All except for Five studies included patients suspected of AA, Wu
two104,114 were single-center studies. White blood cell et al.108 only included patients with RLQ pain, and
(WBC) count was the most commonly reported labora- Goldman et al.14 included patients with undifferenti-
tory test (10 studies) followed by absolute neutrophil ated abdominal pain. Sample size ranged from 9916 to
count (ANC) or percentage of neutrophils (seven 1,395108.
studies). The cutoff point for WBC count was 10,000 Two studies, Mandeville et al.103 and Goldman
cells/mm3 in nine studies and 12,000 cells/mm3 in one et al.,14 reported data on every possible cutoff point
study (Kwan and Nager101). The cutoff point for ANC for PAS (0–10) while three studies (Schneider et al.,94
varied among studies: ≥7,500 cells/mm3 (Zuniga et al.,15 Khanafer et al.,113 and Escriba et al.16) described data
Goldman et al.14) and ≥6,750 cells/mm3 (Sivitz et al.25). on PAS cutoff points 1 to 10. Bachur et al.23 catego-
One study (Bachur et al.114) investigated various cutoff rized the results in the following groups: PAS < 4,
points of WBC count and ANC in three different age PAS = 4–6, and PAS ≥ 7 and Wu et al.108 described
groups (less than 5, 5–12, and older than 12 years). PAS ≥ 7 cutoff point on days 1 to 3 of presentation.
Several studies reported percentage of neutrophils. For the purpose of this review we only included data
Bachur et al.,23 Mandeville et al.,103 and Schneider collected on Day 1 (at presentation).
et al.94 reported neutrophils ≥ 75% and Santillanes We decided to exclude one study, Escriba et al.,16
et al.111 reported neutrophils ≥ 67%. Other variables from final analysis. Escriba et al.16 used “more than”
studied were D-dimer, C-reactive protein (CRP), urine (>) as the definition of cutoff point. It is unclear
ketones, and procalcitonin. what the authors mean by PAS > 10 as PAS = 10
532 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

Table 2
Description of Reviewed Studies: ED-POCUS

Study Participants Criterion Standard ED-POCUS Prevalence (95% CI)


Fox et al., 2007 Inclusion: • Histopathology Operator: EM attending 54% (40-68%)
• Suspected appendicitis • No surgery, F/u 2 physicians and residents
Exclusion: weeks and 3 months Interpreter: Same
• Pregnancy Training: Lecture
• Unable to consent
Sample Size:42
Mean Age: NS
Median Age: NS
Gender: NS
Eliskashvili et al.,2014 Inclusion: • Histopathology Operator: PEM attending 33% (26-41%)
• Suspected appendicitis • No surgery, F/u physicians and fellows
• Age< 21 years 3 weeks Interpreter: Same
Exclusion: Training: 30 minutes lecture
• Unstable Vital Signs plus 30 minutes hands-on
• Dx of AA or IBD practice session
• Prior abdominal CT or US
Sample size: 150
Mean age: 12  5.2 years
Gender: 44% M
Sivitz et al., 2014 Inclusion: • Histopathology Operator: PEM attending 33% (27-39)
• Suspected appendicitis • No surgery, F/u, physicians and fellows
Exclusion: 6 months Interpreter: Same
• Previous abdominal surgery Training: 45 minutes lecture
• Unstable Vital Signs plus 5 supervised practice
Sample Size: 231 scans
Median Age: 10.2 years
Gender: 53% M
Kim et al., 2015 Inclusion: • Histopathology Operator: EM residents 31% (23-40%)
• Suspected appendicitis • No surgery, F/u for Interpreter: Same
• Age< 19 years undetermined duration Training: 1-2 YR experience
Exclusion: with ultrasound plus
• Patients lost to F/u 20 minutes
• Previous CT scan practice session
Sample Size: 115
Mean Age: 10.6  3.3 years
Gender: 56.5% M
Doniger et al, 2016 Inclusion: • Histopathology Operator: EM faculty or 40% (26-55)
• Suspected appendicitis • No surgery, F/u residents, PEM faculty
• Age 2-18 years >2 weeks Interpreter: Same
Exclusion: Training: 30 minutes tutorial
• Pregnancy plus 40 supervised practice
• Previous abdominal imaging scans
Sample Size: 40
Mean Age: 9.26 years
Gender: 50% M

CT = computed tomography; ED-POCUS = Emergency department point-of-care ultrasound; EM = emergency medicine; F/u = follow-up;
IBD = inflammatory bowel disease; M = male; PEM = pediatric emergency medicine; US = ultrasound.

is the maximum score a patient can get on PAS. of AA (Table 8), the highest LR+s were for PAS = 10
We unsuccessfully tried to contact the author to (LR+ = 5.80), PAS ≥ 9 (LR+ = 5.26), and PAS ≥ 8
clarify this point. In the article by Schneider et al.,94 (LR+ = 4.40) making only highest scores (PAS = 8, 9,
“1 – specificity” was incorrectly reported in place of and 10) good predictors of AA. The results were very
“specificity.” After contacting one of the authors and heterogeneous (I2 = 77.2%–85.6%) for the lowest cut-
confirming that this was in fact an error in print, off points of PAS (PAS = 1, 2, and 3) and therefore
we recalculated the reported specificities and used pooled data could not be calculated. In one study on
the data. patients with undifferentiated abdominal pain
Data from six studies were included in the (Table 9), moderate PAS cutoff points had the highest
meta-analysis, five on patients suspected of AA and LR+ (PAS ≥ 5 with LR+ = 4.56, and PAS ≥ 6 with
Goldman et al.14 on patients with undifferentiated LR+ = 4.07). In Goldman et al.,14 PAS ≥ 0 (LR– =
abdominal pain. Across studies on patients suspected 0.01) and PAS ≥ 1 (LR– = 0.24) had the lowest
Table 3
History Findings in Children Suspected of Appendicitis*

Predictors of Pediatric Sample Sensitivity, Specificity,


Appendicitis Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
102
Fever Kentsis et al., 2012 49 46 (26–67) 48 (28–69) 0.88 (0.50–1.57) 1.13 (0.65–1.96)
Khan et al., 2012112 50 41 (21–63) 64 (44–81) 1.15 (0.56–2.32) 0.92 (0.59–1.43)
Sivitz et al., 201425 231 26 (17–38) 72 (65–79) 0.95 (0.60–1.49) 1.02 (0.86–1.20)
Doniger and Kornblith, 2016110 40 38 (15–64) 42 (22–63) 0.64 (0.31–1.31) 1.50 (0.82–2.70)
Pooled data 370 33 (26–42) I2 = 75.3% 0.90 (0.67–1.21) 1.04 (0.90–1.20)
Nausea/vomiting Schneider et al., 200794 588 86 (80–90) 35 (31–40) 1.33 (1.21–1.46) 0.40 (0.28–0.58)
Mandeville et al., 2011103 287 75 (68–82) 36 (28–44) 1.18 (1.01–1.38) 0.67 (0.47–0.96)
Santillanes et al., 2012111 475 73 (66–79) 38 (33–45) 1.19 (1.05–1.35) 0.69 (0.41–0.95)
Kentsis et al., 2012102 49 59 (36–79) 64 (43–82) 1.64 (0.88–3.08) 0.64 (0.36–1.14)
Zuniga et al., 201215 101 79 (59–92) 44 (32–56) 1.40 (1.06–1.85) 0.49 (0.23–1.04)
Khan et al., 2012112 50 73 (50–89) 39 (21–59) 1.19 (0.80–1.77) 0.69 (0.30–1.58)
Huckins et al., 2013104 503 64 (56–72) 63 (58–68) 1.74 (1.45–2.09) 0.57 (0.45–0.72)
Sivitz et al., 201425 231 74 (62–83) 37 (29–45) 1.17 (0.97–1.40) 0.72 (0.47–1.10)
Bachur et al., 201523 728 70 (63–76) 40 (35–44) 1.16 (1.04–1.30) 0.76 (0.60–0.96)
Cayrol et al., 2016105 134 42 (29–57) 77 (66–85) 1.82 (1.10–3.02) 0.75 (0.58–0.97)
Doniger and Kornblith, 2016110 40 75 (71–76) 33 (16–55) 1.13 (0.75–1.68) 0.75 (0.27–2.08)
Pooled data 3,186 I2 = 79.9% I2 = 91.6% 1.30 (1.19–1.41) 0.65 (0.57–0.73)
Anorexia Schneider et al., 200794 588 73 (66–79) 44 (39–49) 1.29 (1.15–1.46) 0.62 (0.48–0.80)
Mandeville et al., 2011103 287 74 (67–81) 38 (30–47) 1.19 (1.02–1.41) 0.68 (0.48–0.96)
Santillanes et al., 2012111 475 80 (74–86) 43 (37–50) 1.42 (1.25–1.61) 0.45 (0.33–0.62)
Zuniga et al., 201215 101 89 (72–98) 33 (22–45) 1.33 (1.08–1.63) 0.33 (0.11–1.00)
Khan et al., 2012112 50 86 (65–97) 32 (16–52) 1.27 (0.94–1.72) 0.42 (0.13–1.38)
Huckins et al., 2013104 503 73 (65–80) 45 (40–50) 1.32 (1.15–1.52) 0.60 (0.45–0.81)
Sivitz et al., 201425 231 74 (62–83) 51 (43–59) 1.50 (1.22–1.85) 0.52 (0.34–0.78)
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org

Bachur et al., 201523 728 71 (64–77) 47 (42–40) 1.31 (1.17–1.48) 0.63 (0.50–0.80)
Doniger and Kornblith, 2016110 40 75 (47–93) 54 (33–74) 1.64 (0.97–2.74) 0.46 (0.18–1.16)
Pooled data 3,003 75 (72–78) 44 (42–46) 1.33 (1.26–1.40) 0.58 (0.52–0.65)
Pain migration to RLQ Schneider et al., 200794 588 49 (42–56) 73 (69–78) 1.85 (1.49–2.30) 0.69 (0.60–0.80)
Mandeville et al., 2011103 287 45 (37–53) 64 (56–73) 1.27 (0.95–1.69) 0.85 (0.70–1.03)
Zuniga et al., 201215 101 46 (28–66) 77 (65–86) 1.99 (1.12–3.55) 0.70 (0.48–1.01)
Kentsis et al., 2012102 49 63 (41–81) 72 (51–88) 2.23 (1.11–4.50) 0.52 (0.29–0.92)
Huckins et al., 2013104 503 69 (61–77) 61 (56–66) 1.77 (1.49–2.09) 0.50 (0.39–0.65)
Sivitz et al., 201425 231 50 (38–62) 68 (60–75) 1.55 (1.13–2.14) 0.74 (0.58–0.95)
Bachur et al., 201523 728 50 (43–57) 75 (71–79) 1.99 (1.63–2.43) 0.67 (0.58–0.77)
Cayrol et al., 2016105 134 33 (20–47) 80 (70–88) 1.68 (0.93–3.02) 0.84 (0.67–1.04)
Pooled data 2,621 I2 = 77.6% I2 = 77% 1.75 (1.58–1.94) 0.70 (0.62–0.79)
Pain RLQ Santillanes et al., 2012111 475 91 (86–95) 36 (30–42) 1.42 (1.28–1.57) 0.25 (0.15–0.40)
Khan et al., 2012112 50 82 (60–95) 39 (22–59) 1.35 (0.94–1.92) 0.46 (0.17–1.25)
Cayrol et al., 2016105 134 75 (61–86) 38 (27–49) 1.21 (0.96–1.52) 0.66 (0.38–1.14)
Pooled data 703 I2 = 77.4 37 (32–42) 1.38 (1.26–1.51) I2 = 72.5
Periumbilical Santillanes et al., 2012111 475 50 (43–57) 50 (44–56) 1.0 (0.83–1.21) 0.99 (0.82–1.19)
LLQ Khan et al., 2012112 50 4 (0.1–22) 99 (82–100) 1.27 (0.08–19.22) 0.99 (0.88–1.11)
Epigastric Khan et al., 2012112 50 9 (1–29) 82 (62–93) 0.51 (0.10–2.38) 1.10 (0.95–1.28)
Diffuse Santillanes et al., 2012111 475 30 (24–37) 72 (67–78) 1.08 (0.81–1.45) 0.97 (0.86–1.09)
Khan et al., 2012112 50 4.5 (1–23) 96 (82–100) 1.27 (0.08–19) 0.99 (0.88–1.11)
Pooled data 525 I2 = 88.3% I2 = 90.6% 1.09 (0.81–1.45) 0.98 (0.90–1.06)

(Continued)
533
534

Table 3 (continued)

Predictors of Pediatric Sample Sensitivity, Specificity,


Appendicitis Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
Symptom duration < 12 h Kentsis et al., 2012102 49 29 (13–51) 55 (35–76) 0.66 (0.31–1.42) 1.26 (0.82–1.95)
Huckins et al., 2013104 503 24 (17–31) 72 (67–76) 0.83 (0.59–1.16) 1.07 (0.95–1.19)
Bachur et al., 201523 728 19 (14–25) 77 (73–81) 0.86 (0.63–1.16) 1.04 (0.96–1.12)
Bachur et al., 2016114 2,133 24 (21–27) 67 (64–70) 0.73 (0.64–0.84) 1.13 (1.07–1.19)
Pooled data 3,413 23 (21–26) I2 = 86% 0.76 (0.68–0.86) 1.09 (1.04–1.15)
Symptom duration Kentsis et al., 2012102 49 29 (13–51) 84 (64–95) 1.82 (0.61–5.44) 0.84 (0.62–1.15)
12–24 h Huckins et al., 2013104 503 38 (30–47) 66 (61–71) 1.12 (0.87–1.45) 0.94 (0.81–1.09)
Bachur et al., 201523 728 33 (27–40) 72 (67–75) 1.17 (0.92–1.48) 0.93 (0.84–1.04)
Bachur et al., 2016114 2,133 34 (31–37) 68 (66–71) 1.07 (0.95–1.21) 0.97 (0.91–1.03)
Pooled data 3,413 35 (30–40) 69 (67–71) 1.10 (1.00–1.22) 0.95 (0.91–1.00)
Symptom duration Kentsis et al., 2012102 49 38 (19–59) 68 (46–85) 1.17 (0.54–2.53) 0.92 (0.61–1.38)
24–48 h Huckins et al., 2013104 503 22 (15–29) 80 (75–84) 1.07 (0.74–1.56) 0.98 (0.89–1.08)
Bachur et al., 201523 728 28 (22–35) 78 (75–82) 1.30 (1.0–1.73) 0.92 (0.83–1.00)
Bachur et al., 2016114 2,133 30 (27–34) 75 (73–78) 1.23 (1.07–1.42) 0.92 (0.87–0.97)
Pooled data 3,413 29 (27–32) 77 (75–79) 1.23 (1.09–1.38) 0.93 (0.87–0.97)
Symptom duration Kentsis et al., 2012102 49 4 (0.0–21) 96 (80–100) 1.04 (0.07–15.7) 1.00 (0.89–1.12)
48–72 h Huckins et al., 2013104 503 17 (11–24) 82 (78–86) 0.95 (0.62–1.46) 1.01 (0.93–1.10)
Bachur et al., 201523 728 10 (7–15) 92 (89–94) 1.30 (0.79–2.12) 0.97 (0.93–1.03)
Bachur et al., 2016114 2,133 11 (9–14) 89 (87–91) 1.06 (0.83–1.36) 0.99 (0.96–1.02)
Pooled data 3,413 12 (10–14) I2 = 85.5% 1.07 (0.88–1.30) 0.99 (0.97–1.01)
Symptom duration > 72 h Bachur et al., 201523 728 5 (2–8) 89 (85–91) 0.41 (0.21–0.79) 1.08 (1.03–1.12)
Obstipation Santillanes et al., 2012111 475 17 (11–23) 91 (87–95) 1.96 (1.17–3.28) 0.91 (0.85–0.98)
Diarrhea Santillanes et al., 2012111 475 22 (16–28) 82 (77–86) 1.21 (0.84–1.75) 0.95 (0.87–1.05)

*Pooled data are reported only when I-square (I2) ≤ 50%. See Table 6 for test characteristics of “fever” based on temperature cutoff point used.
Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 535

Table 4
History, Physical Examination and Laboratory Tests Findings in Children With Undifferentiated Abdominal Pain

Predictors of Sample Sensitivity, Specificity,


Pediatric Appendicitis Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
Fever O’Shea et al., 1988109 246 75 (53–90) 78 (72–83) 3.4 (2.42–4.76) 0.32 (0.16–0.64)
Nausea or vomiting O’Shea et al., 1988109 246 79 (58–93) 64 (57–70) 2.2 (1.68–2.88) 0.33 (0.15–0.71)
Goldman et al., 200814 849 75 (66–82) 54 (50–57) 1.62 (1.42–1.84) 0.47 (0.34–0.64)
Pooled data 1,095 75 (68–82) I2 = 86% I2 = 75% 0.45 (0.33–0.60)
Anorexia O’Shea et al., 1988109 246 21 (7–42) 73 (66–78) 0.77 (0.34–1.70) 1.08 (.087–1.35)
Goldman et al., 200814 849 68 (59–76) 64 (61–68) 1.92 (1.65–2.24) 0.49 (0.38–0.64)
Pooled data 1,095 I2 = 94.7% I2 = 82.4% I2 = 80.7% I2 = 96.6%
Pain migration to RLQ Goldman et al., 200814 849 46 (37–56) 90 (88–92) 4.81 (3.59–6.44) 0.59 (0.50–0.70)
Cough/hop pain Goldman et al., 200814 849 72 (63–79) 91 (88–93) 7.64 (5.94–9.83) 0.31 (0.24–0.42)
Right iliac fossa tenderness Goldman et al., 200814 849 79 (71–86) 83 (80–86) 4.74 (3.94–5.70) 0.24 (0.17–0.35)
T > 38°C Goldman et al., 200814 849 59 (50–68) 79 (76–82) 2.80 (2.28–3.43) 0.52 (0.42–0.64)
Lethargy O’Shea et al., 1988109 246 4.2 (0.11–21) 95 (91–98) 0.84 (0.11–6.23) 1.01 (0.92–1.10)
Diarrhea O’Shea et al., 1988109 246 33 (15–55) 87 (82–941) 2.55 (1.32–4.94) 0.77 (0.58–1.02)
Dysuria O’Shea et al., 1988109 246 0.0 (0.0–13) 96 (93–98) 0.59 (0.35–10.0) 1.00 (0.95–1.07)
Nausea without vomiting O’Shea et al., 1988109 246 29 (13–51) 79 (73–84) 1.38 (0.70–2.70) 0.90 (0.69–1.17)
WBC ≥ 10,000 Goldman et al., 200814 308* 88 (80–93) 57 (50–64) 2.04 (1.71–2.43) 0.22 (0.13–0.36)
ANC ≥ 7,500 Goldman et al., 200814 289† 83 (74–90) 64 (57–71) 2.33 (1.89–2.88) 0.26 (0.17–0.41)

Pooled data are reported only when I-square (I2) ≤50%


ANC = absolute neutrophil count (cells/mm3); RLQ = right lower quadrant; T = temperature; WBC = white blood cells.
*Data available only for a subgroup of total population (308/849).
†Data available only for a subgroup of total population (289/849).

LR– and therefore PAS = 0 and PAS = 1 were most Fox106 and Doniger and Kornblith110 excluded preg-
suggestive of absence of AA. nant patients. Doniger and Kornblith110 also excluded
those with recent abdominal imaging and Kim
et al.107 did not specify any exclusion criteria. The
ED-POCUS
duration of follow-up in patients who were managed
Five studies24,25,106,107,109 met our inclusion criteria. nonsurgically varied from 2 weeks110 to 6 months.25
All five studies included patients suspected of One study107 did not specify the duration of follow-
AA (Table 2). While four studies were done exclu- up. In four studies,24,25,106,110 the treating and the
sively on pediatric patients, Fox et al.106 included both enrolling physician could be the same. Kim et al.107
adult and pediatric patients; however, they presented did not provide details about their treating physicians.
data for their pediatric population (n = 42) separately. In all studies ED residents and attending physicians
Sivitz et al.25 reported number of positive and nega- or pediatric emergency medicine fellows and attending
tive ED-POCUS studies, which was slightly higher physicians obtained and interpreted the ED-POCUS.
than the sample size suggesting that some patients Fox et al.106 limited the duration of ED-POCUS to 5
received more than one ED-POCUS study. Since the minutes, whereas the rest of the studies did not use
number of scans was close to the sample size (264 such limitation.
ED-POCUS studies in 231 patients), we decided to Elikashvili et al.24 reported significantly higher per-
include this study in our review. In one study (Kim centage of equivocal results compared to all other stud-
et al.107), both EM residents and attending physicians ies in this group. A high number of equivocal results
(either on site or via teleultrasonography) performed in Elikashvili et al.24 can be attributed to the fact that
ED-POCUS on the same group of participants. To full visualization of a normal appendix was mandatory
avoid any overlapping data, we decided to include to consider an ED-POCUS scan negative whereas
only the ED-POCUS scans done on site by residents. other studies in this group did not mandate a full visu-
Sample size varied widely between studies ranging alization. Due to high prevalence of equivocal results
from 40 (Doniger and Kornblith110) to 264 (Sivitz in Elikashvili et al.,24 we decided to exclude this study
et al.25). Four studies24,25,106,110 excluded patients who from our final analysis. Across the remaining four
had unstable vital signs. Sivitiz et al.25 excluded studies,25,106,107,109 ED-POCUS had a sensitivity of
patients with history of abdominal surgery while 86% (95% CI = 79%–90%), specificity of 91% (95%
536 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

Table 5
Physical Examination Findings in Children Suspected of Appendicitis

Predictors of Sample Sensitivity, Specificity,


Pediatric Appendicitis Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
Fever* Schneider et al., 200794 588 46 (39–53) 55 (50–60) 1.03 (0.85–1.24) 0.98 (0.84–1.15)
Mandeville et al., 2011103 287 50 (42–58) 64 (55–72) 1.37 (1.04–1.80) 0.79 (0.65–0.97)
Santillanes et al., 2012111 475 31 (25–38) 67 (61–73) 0.95 (0.73–1-24) 1.02 (0.93–1.13)
Zuniga et al., 201215 101 46 (28–66) 68 (57–79) 1.47 (0.87–2.48) 0.78 (0.54–1.14)
Huckins et al., 2013104 503 25 (18–33) 84 (79–87) 1.52 (1.05–2.20) 0.90 (0.81–1.00)
Bachur et al., 201523 728 31 (25–37) 71 (67–75) 1.05 (0.82–1.33) 0.98 (0.89–1.09)
Cayrol et al., 2016105 134 42 (29–57) 60 (48–70) 1.05 (0.70–1.59) 0.97 (0.72–1.29)
Pooled data 2,816 I2 = 83% I2 = 92.4% 1.13 (0.99–1.29) 0.94 (0.89–1.00)
RLQ tenderness Schneider et al., 200794 588 83 (77–88) 37 (32–42) 1.32 (1.19–1.45) 0.47 (0.33–0.65)
Kwan and Nager, 2010101 209 78 (70–85) 23 (15–33) 1.02 (0.88–1.18) 0.93 (0.56–1.54)
Mandeville et al., 2011103 287 92 (87–96) 11 (6–17) 1.03 (0.96–1.11) 0.73 (0.35–1.52)
Santillanes et al., 2012111 475 95 (90–97) 32 (27–38) 1.40 (1.28–1.53) 0.16 (0.08–0.30)
Zuniga et al., 201215 101 89 (72–98) 33 (22–45) 1.33 (1.08–1.63) 0.33 (0.11–1.00)
Khan et al., 2012112 50 100 (84–100) 7 (0.9–23) 1.07 (0.96–1.19) 0.06 (0.0–35.58)
Huckins et al., 2013104 503 99 (96–100) 14 (11–18) 1.15 (1.10–1.21) 0.05 (0.01–0.36)
Sivitz et al., 201425 231 96 (89–99) 8 (4–13) 1.04 (0.98–1.11) 0.51 (0.15–1.75)
Bachur et al., 201523 728 87 (82–91) 40 (35–44) 1.45 (1.32–1.58) 0.32 (0.22–0.46)
Doniger and Kornblith, 2016110 40 100 (79–100) 25 (10–47) 1.31 (1.02–1.68) 0.11 (0.00–1.90)
Pooled data 3,212 I2 = 86.3% I2 = 94.5% I2 = 90.5% I2 = 71.1%
Cough/hop pain Schneider et al., 200794 588 68 (60–74) 64 (59–69) 1.89 (1.60–2.22) 0.51 (0.41–0.63)
Mandeville et al., 2011103 287 83 (76–89) 46 (38–55) 1.55 (1.30–1.84) 0.36 (0.24–0.54)
Zuniga et al., 201215 101 71 (51–87) 48 (36–60) 1.37 (1.00–1.89) 0.60 (0.32–1.12)
Sivitz et al., 201425 231 64 (53–75) 66 (58–73) 1.89 (1.43–2.48) 0.54 (0.39–0.75)
Bachur et al., 201523 728 69 (62–75) 52 (48–57) 1.44 (1.27–1.64) 0.60 (0.48–0.74)
Pooled data 1,935 I2 = 74.6% I2 = 84.8% 1.61 (1.42–1.83) 0.52 (0.45–0.61)
RLQ rebound tenderness Schneider et al., 200794 588 48 (41–55) 77 (72–81) 2.05 (1.63–2.59) 0.68 (0.59–0.79)
Kwan and Nager, 2010101 209 15 (9–23) 90 (83–96) 1.54 (0.72–3.30) 0.94 (0.85–1.04)
Mandeville et al., 2011103 287 47 (39–55) 71 (62–78) 1.59 (1.17–2.18) 0.75 (0.52–0.90)
Santillanes et al., 2012111 475 36 (29–43) 87 (83–91) 2.83 (1.97–4.07) 0.73 (0.65–0.82)
Zuniga et al., 201215 101 50 (31–69) 71 (59–81) 1.74 (1.04–2.92) 0.70 (0.47–1.05)
Khan et al., 2012112 50 68 (45–86) 68 (47–84) 2.12 (1.15–3.90) 0.47 (0.24–0.91)
Huckins et al., 2013104 503 51 (42–59) 80 (75–84) 2.49 (1.92–3.24) 0.62 (0.52–0.74)
Sivitz et al., 201425 231 62 (50–73) 79 (71–85) 2.91 (1.05–4.12) 0.49 (0.36–0.65)
Bachur et al., 201523 728 38 (32–45) 84 (80–87) 2.33 (1.80–3.02) 0.74 (0.66–0.83)
Cayrol et al., 2016105 134 58 (43–71) 67 (56–71) 1.75 (1.19–2.58) 0.63 (0.44–0.90)
Doniger and Kornblith, 2016110 40 50 (25–75) 92 (73–99) 6.0 (1.46–24.6) 0.54 (0.33–0.90)
Pooled data 3,346 I2 = 86.9% I2 = 78.6% 2.19 (1.91–2.51) I2 = 78.3%
Guarding Khan et al., 2012112 50 59 (36–79) 64 (44–81) 1.65 (0.90–3.03) 0.63 (0.36–1.12)
Santillanes et al., 2012111 475 70 (63–76) 69 (63–74) 2.25 (1.84–2.74) 0.44 (0.35–0.55)
Huckins et al., 2013104 503 74 (66–81) 68 (63–73) 2.32 (1.93–2.79) 0.38 (0.28–0.51)
Bachur et al., 201523 728 65 (59–72) 65 (61–69) 1.87 (1.60–2.18) 0.53 (0.44–0.65)
Pooled data 1,756 69 (65–73) 67 (64–69) 2.09 (1.83–2.37) 0.47 (0.39–0.56)
RUQ tenderness Kwan and Nager, 2010101 209 6 (2–12) 89 (81–95) 0.57 (0.23–1.45) 1.05 (0.97–1.14)
LLQ tenderness Kwan and Nager, 2010101 209 13 (7–20) 85 (76–91) 0.87 (0.44–1.72) 1.02 (0.91–1.14)
LUQ tenderness Kwan and Nager, 2010101 209 2 (0–6) 97 (91–99) 0.54 (0.09–3.19) 1.02 (0.97–1.06)
Epigastric tenderness Kwan and Nager, 2010101 209 14 (8–21) 86 (77–92) 1.00 (0.51–1.98) 0.99 (0.89–1.11)
Suprapubic tenderness Kwan and Nager, 2010101 209 5 (2–11) 96 (89–98) 1.23 (0.36–4.22) 0.99 (0.93–1.05)
Periumbilical tenderness Kwan and Nager, 2010101 209 22 (15–30) 72 (62–81) 0.79 (0.49–1.27) 1.08 (0.92–1.27)
Santillanes et al., 2012111 475 42 (35–49) 63 (57–69) 1.13 (0.90–1.41) 0.93 (0.80–1.08)
Pooled data 684 I2 = 92.4% I2 = 64% 1.00 (0.72–1.39) 1.00 (0.86–1.17)
Diffuse tenderness Cayrol et al., 2016105 134 71 (57–83) 45 (34–57) 1.30 (1.00–1.68) 0.64 (0.39–1.04)
Santillanes et al., 2012111 475 27 (21–34) 78 (72–83) 1.22 (0.88–1.69) 0.94 (0.84–1.04)
Absent/decreased Sanillanes et al., 2012111 475 40 (32–47) 87 (82–91) 3.06 (2.14–4.38) 0.69 (0.61–0.78)
bowel sounds Khan et al., 2012112 50 14 (3–35) 98 (84–100) 7.64 (0.40–144) 0.88 (0.74–1.05)
Psoas sign Santillanes et al., 2012111 475 38 (31–46) 88 (83–91) 3.15 (2.17–4.58) 0.75 (0.62–0.79)
Obturator sign Santillanes et al., 2012111 475 34 (27–41) 90 (86–94) 3.52 (2.30–5.39) 0.73 (0.65–0.82)
Rovsing’s sign Santillanes et al., 2012111 475 34 (27–42) 91 (87–94) 3.94 (2.54–6.11) 0.72 (0.65–0.80)
Huckins et al., 2013104 503 36 (28–44) 89 (85–92) 3.24 (2.23–4.71) 0.72 (0.63–0.82)
Pooled data 978 35 (30–40) 90 (87–92) 3.52 (2.65–4.68) 0.72 (0.66–0.78)

Pooled data are reported only when I-square (I2) ≤ 50%.


*See Table 6 for test characteristics of “fever” based on temperature cutoff point used
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 537

Table 6
Fever in Patients Suspected of Appendicitis

Predictors of Sample Sensitivity, Specificity,


Pediatric Appendicitis Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
Objective fever in ED Santillanes et al., 2012111 475 31 (25–38) 67 (61–73) 0.95 (0.73–1-24) 1.02 (0.93–1.13)
T > 38°C Bachur et al., 201523 728 31 (25–37) 71 (67–75) 1.05 (0.82–1.33) 0.98 (0.89–1.09)
T > 37.3–37.5°C Schneider et al., 200794 588 46 (39–53) 55 (50–60) 1.03 (0.85–1.24) 0.98 (0.84–1.15)
Mandeville et al., 2011103 287 50 (42–58) 64 (55–72) 1.37 (1.04–1.80) 0.79 (0.65–0.97)
Zuniga et al., 201215 101 46 (28–66) 69 (57–79) 1.47 (0.87–2.48) 0.78 (0.54–1.14)
Huckins et al., 2013104 503 25 (18–33) 84 (79–87) 1.52 (1.05–2.20) 0.90 (0.81–1.00)
Cayrol et al., 2016105 134 42 (29–57) 60 (48–70) 1.05 (0.70–1.59) 0.97 (0.72–1.29)
Pooled data 1,613 I2 = 82.9 I2 = 94.8% 1.22 (1.02–1.46) 0.90 (0.83–0.97)

Pooled data are reported only when I-square (I2) ≤ 50%.

Table 7
Laboratory Tests in Patients Suspected of Appendicitis

Predictors of Sample Sensitivity, Specificity,


Pediatric Appendicitis Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
WBC ≥ 10,000 Schneider et al., 2007 94
588 90 (85–94) 52 (47–57) 1.88 (1.68–2.10) 0.19 (0.13–0.30)
Mandeville et al., 2011103 287 83 (76–89) 63 (54–71) 2.24 (1.78–2.83) 0.27 (0.18–0.39)
Zuniga et al., 201215 101 93 (77–91) 49 (37–61) 1.83 (1.43–2.35) 0.14 (0.04–0.56)
Santillanes et al., 2012111 475 89 (84–93) 49 (42–55) 1.73 (1.53–1.96) 0.22 (0.15–0.34)
Sivitz et al., 201425 231 86 (76–93) 64 (56–71) 2.37 (1.88–2.98) 0.23 (0.13–0.40)
Bachur et al., 201523 728 83 (77–88) 64 (60–68) 2.29 (2.01–2.61) 0.27 (0.20–0.37)
Cayrol et al., 2016105 134 88 (77–96) 60 (48–70) 2.20 (1.66–2.91) 0.19 (0.09–0.42)
Bachur et al., 2016114 2,133 90 (88–92) 54 (51–57) 1.96 (1.84–2.09) 0.18 (0.15–0.22)
Pooled data 4,677 88 (87–90) 56 (54–58) 2.01 (1.86–2.17) 0.21 (0.19–0.25)
WBC > 12,000 Kwan and Nager, 2010101 209 71 (62–79) 66 (55–75) 2.09 (1.54–2.84) 0.44 (0.32–0.60)
ANC ≥ 6,750 Sivitz et al., 201425 231 91 (82–96) 57 (49–65) 2.10 (1.73–2.55) 0.16 (0.08–0.33)
ANC ≥ 7,500 Zuniga et al., 201215 101 96 (82–100) 56 (44–68) 2.20 (1.68–2.88) 0.06 (0.01–0.44)
Neutrophils ≥ 67% Santillanes et al., 2012111 475 96 (92–98) 39 (33–45) 1.57 (1.43–1.74) 0.11 (0.05–0.21)
Neutrophils ≥ 75% Schneider et al., 200794 588 84 (78–89) 57 (52–62) 1.95 (1.71–2.22) 0.28 (0.20–0.39)
Mandeville et al., 2011103 287 77 (69–83) 64 (55–72) 2.11 (1.66–2.69) 0.36 (0.26–0.50)
Bachur et al., 201523 728 75 (68–80) 64 (60–68) 2.09 (1.97–3.13) 0.39 (0.31–0.50)
Pooled data 1,603 I2 = 67.9% I2 = 64.1% 2.02 (1.85–2.21) 0.35 (0.28–0.43)
CRP > 3 mg/dL Kwan and Nager, 2010101 209 70 (60–79) 65 (53–75) 1.98 (1.47–2.68) 0.47 (0.39–0.64)
Cayrol et al., 2016105 134 38 (25–53) 85 (76–92) 2.63 (1.41–4.91) 0.72 (0.57–0.91)
Pooled data 343 I2 = 93.3% I2 = 90% 2.10 (1.61–2.76) I2 = 81.8%
WBC > 12,000 + CRP > 3 mg/dL Kwan and Nager, 2010101 209 42 (33–51) 91 (86–97) 4.36 (2.26–8.42) 0.64 (0.54–0.76)
Positive urine ketone Sivitz et al., 201425 231 37 (26–49) 75 (67–82) 1.46 (0.98–2.19) 0.84 (0.70–1.03)
D-dimer > 230 ng/mL Cayrol et al., 2016105 134 40 (27–55) 80 (70–88) 2.07 (1.19–3.59) 0.74 (0.58–0.95)
Procalcitonin > 0.39 ng/dL Khan et al., 2012112 50 25 (8–45) 92 (76–99) 3.25 (0.68–14.0) 0.80 (0.65–1.07)
Three-marker panel* Huckins et al., 2013104 503 96 (92–99) 43 (38–48) 1.70 (1.54–1.87) 0.08 (0.03–0.19)

Pooled data are reported only when I-square (I2) ≤ 50%.


ANC = absolute neutrophil count (cells/mm3); WBC = white blood cells.
*Mathematical combination of WBC, CRP, and myeloid related protein 8/14 (MRP 8/14).

CI = 87%–94%), LR+ = 9.24 (95% CI = 6.42– 0.82). A meeting was held between two reviewers (RB,
13.28), and LR– = 0.17 (95% CI = 0.09–0.30) mak- MH) and the third author (RS) to resolve any disagree-
ing positive ED-POCUS a good predictor of AA while ments by consensus and all authors agreed 100% on
negative ED-POCUS considerably decreases the proba- the final QUADAS-2 scoring (Figure 3).
bility of AA (Table 10, Figure 2). A sensitivity analysis
adding Elikashvili et al.24 results did not drastically Patient Selection. We found several studies at
change LR+ (9.56 vs 9.24) while significantly increased risk of bias due to inappropriate exclusion: Several
the heterogeneity. studies23,25,94,101,103 excluded patients with history of
any abdominal surgery (and not exclusively appendec-
QUADAS-2 Analysis of Included Studies tomy), abdominal trauma,104,109 or abdominal
Initial inter-rater reliability among the two QUADAS imaging.94,103 Inappropriate exclusion reduces the gen-
reviewers was substantial (j = 0.75, 95% CI = 0.61– eralizability of the results. Certain exclusions can result
538 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

Table 8
PAS in Patients Suspected of AA

Predictors of Sample Sensitivity, Specificity,


Pediatric Appendicitis Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
PAS ≥ 0 Mandeville et al., 2011103 287 100 (98–100) 0 (0–0) 1.00 (0.99–1.01) 0.85 (0.02–42.7)
PAS ≥ 1 Schneider et al., 200794 588 100 (98–100) 1 (0.6–3) 1.01 (1.00–1.03) 0.15 (0.00–2.63)
Mandeville et al., 2011103 287 94 (89–97) 1 (1–4) 0.95 (0.91–0.99) 7.67 (0.98–59.7)
Khanafer et al., 2016113 180 100 (93–100) 1 (0.2–5) 1.01 (0.99–1.04) 0.11 (0–64)
Pooled data 1,055 I2 = 88.2% 1 (1–3) I2 = 85.6% I2 = 63.9%
PAS ≥ 2 Schneider et al., 200794 588 100 (98–100) 4 (2–6) 1.03 (0.97–1.09) 0.07 (0.00–1.11)
Mandeville et al., 2011103 287 94 (89–97) 2 (0–7) 0.96 (0.92–1.01) 2.56 (0.71–9.24)
Khanafer et al., 2016113 180 100 (93–100) 4.8 (2–10) 1.04 (0.99–1.09) 0.17 (0.01–3.02)
Pooled data 1,055 I2 = 88.8 3.7% (2–5) I2 = 79.6% I2 = 76.3%
PAS ≥ 3 Schneider et al., 200794 588 100 (98–100) 12 (0.9–16) 1.14 (1.10–1.18) 0.02 (0.01–0.32)
Mandeville et al., 2011103 287 93 (89–97) 8 (4–14) 1.02 (0.96–1.09) 0.77 (0.34–1.77)
Khanafer et al., 2016113 180 98 (90–100) 13 (7–20) 1.13 (1.04–1.21) 0.14 (0.02–1.04)
Pooled data 1,055 I2 = 88.3% 11.7% (9–14) I2 = 77.2% I2 = 84.6%
PAS ≥ 4 Schneider et al., 200794 588 96 (92–98) 26 (21–30) 1.29 (1.21–1.38) 0.15 (0.07–0.31)
Mandeville et al., 2011103 287 93 (89–97) 15 (10–22) 1.10 (1.02–1.20) 0.43 (0.21–0.88)
Khanafer et al., 2016113 180 91 (80–97) 23 (16–31) 1.18 (1.04–1.34) 0.39 (0.16–0.96)
Pooled data 1,055 94 (91–98) 23 (20–26) I2 = 76.1% 0.30 (0.16–0.55)
PAS ≥ 5 Schneider et al., 200794 588 92 (88–96) 46 (41–51) 1.73 (1.57–1.91) 0.15 (0.09–0.25)
Mandeville et al., 2011103 287 90 (84–94) 30 (23–39) 1.29 (1.14–1.46) 0.34 (0.20–0.58)
Khanafer et al., 2016113 180 91 (80–97) 39 (31–48) 1.50 (1.24–1.81) 0.23 (0.09–0.55)
2
Pooled data 1,055 91 (88–94) I = 82% I2 = 85.5% 0.23 (0.13–0.39)
PAS ≥ 6 Schneider et al., 200794 588 82 (77–88) 65 (60–70) 2.38 (2.05–2.76) 0.26 (0.19–0.36)
Mandeville et al., 2011103 287 88 (82–93) 50 (41–59) 1.77 (1.48–2.12) 0.23 (0.15–0.37)
Khanafer et al., 2016113 180 82 (69–91) 56 (47–65) 1.88 (1.48–2.38) 0.32 (0.09–0.55)
2
Pooled data 1,055 85 (81–88) I = 80.9% 2.01 (1.64–2.45) 0.26 (0.21–0.33)
PAS ≥ 7 Schneider et al., 200794 588 70 (63–76) 78 (74–82) 3.16 (2.57–3.89) 0.39 (0.31–0.48)
Mandeville et al., 2011103 287 80 (73–86) 67 (58–75) 2.40 (1.86–3.09) 0.30 (0.21–0.42)
Wu et al., 2012108 1,395 82 (79–85) 82 (78–86) 4.68 (3.87–5.66) 0.22 (0.19–0.25)
Bachur et al., 201523 728 59 (52–66) 81 (77–84) 3.11 (2.52–3.84) 0.50 (0.43–0.60)
Khanafer et al., 2016113 180 69 (55–81) 72 (63–80) 2.47 (1.77–3.44) 0.43 (0.28–0.65)
Pooled data 3,178 I2 = 92.7% I2 = 79.5% I2 = 83.8% I2 = 93.3%
PAS ≥ 8 Schneider et al., 200794 588 50 (43–58) 90 (86–93) 5.04 (3.63–7.00) 0.55 (0.48–0.63)
Mandeville et al., 2011103 287 66 (58–74) 80 (73–87) 3.37 (2.35–4.85) 0.42 (0.33–0.53)
Zuniga et al., 201215 101 61 (41–78) 93 (85–98) 8.86 (3.62–21.7) 0.42 (0.27–0.67)
Khanafer et al., 2016113 180 56 (42–70) 86 (78–91) 3.91 (2.41–6.37) 0.51 (0.37–0.69)
Pooled data 1,156 I2 = 62.6% I2 = 72% 4.40 (3.26–5.95) 0.49 (0.42–0.57)
PAS ≥ 9 Schneider et al., 200794 588 28 (22–35) 96 (94–98) 7.37 (4.28–12.7) 0.74 (0.68–0.81)
Mandeville et al., 2011103 287 44 (36–52) 92 (86–96) 5.27 (2.91–9.53) 0.61 (0.53–0.71)
Khanafer et al., 2016113 180 26 (15–39) 92 (86–96) 3.18 (1.50–6.71) 0.81 (0.69–0.95)
Pooled data 1,055 I2 = 82% 94 (92–96) 5.26 (3.34–8.29) 0.72 (0.62–0.83)
PAS = 10 Schneider et al., 200794 588 9 (5–13) 99 (98–100) 16.49 (3.84–70.6) 0.92 (0.88–0.96)
Mandeville et al., 2011103 287 13 (8–19) 98 (94–100) 5.68 (1.73–18.7) 0.89 (0.83–0.95)
Khanafer et al., 2016113 180 7 (2–17) 97 (92–99) 2.27 (0.59–8.76) 0.96 (0.88–1.04)
Pooled data 1,055 10 (7–13) 98.6 (97–99) 5.80 (1.97–17.11) 0.92 (0.89–0.95)
PAS = 0-3 Bachur et al., 201523 728 5 (3–9) 71 (67–75) 0.18 (0.10–0.32) 1.34 (1.26–1.43)
PAS = 4-6 Bachur et al., 201523 728 36 (29–43) 48 (44–53) 0.69 (0.57–0.84) 1.33 (1.16–1.52)

Pooled data are reported only when I-square (I2) ≤ 50%.


PAS = Pediatric Appendicitis Score.

in missing milder cases of AA. For instance, exclusion Index Test. In all studies, the interpreter of the
of all patients without surgical consultation, imaging index test (history and physical examination, laboratory
studies, or laboratory tests.15,23,102,113,114 Several stud- tests, PAS, or ED-POCUS) was blinded to the refer-
ies15,16,23,94 excluded all patients in whom missing ence test (operative report and histopathology). In all
data prevented investigators from calculating PAS, of the studies on laboratory tests or ED-POCUS, crite-
which can introduce significant bias. It is unclear how ria for a positive test were prespecified. For physical
this bias skews the results; more severe cases of AA examination, whether to qualify a finding as positive
might have received less workup and were sent straight or negative was left at the discretion of the treating
to surgery and therefore miss data for calculating PAS. physician.
On the other hand, patients least suspected of having
AA might have been discharged without any labora- Reference Test. Surgery and histopathologic exam-
tory tests and therefore miss data for calculating PAS. ination of removed tissue was used as the reference test
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 539

Table 9
PAS in Patients with Abdominal Pain

Predictors of Pediatric Sample Sensitivity, Specificity,


Appendicitis (PAS) Studies Size % (95% CI) % (95% CI) LR+(95% CI) LR–(95% CI)
≥0 Goldman et al., 200814 849 100 (97–100) 27 (24–30) 1.36 (1.30–1.43) 0.01 (0.00–0.24)
≥1 Goldman et al., 200814 849 87 (80–92) 55 (51–59) 1.93 (1.74–2.15) 0.24 (0.15–0.38)
≥2 Goldman et al., 200814 849 68 (59–76) 73 (70–76) 2.53 (2.14–3.00) 0.43 (0.33–0.57)
≥3 Goldman et al., 200814 849 50 (41–60) 83 (80–86) 2.98 (2.35–3.78) 0.60 (0.50–0.72)
≥4 Goldman et al., 200814 849 40 (31–49) 90 (88–92) 3.96 (2.91–5.39) 0.67 (0.58–0.77)
≥5 Goldman et al., 200814 849 28 (20–36) 94 (92–96) 4.56 (3.04–6.84) 0.77 (0.69–0.86)
≥6 Goldman et al., 200814 849 16 (10–24) 96 (94–97) 4.07 (2.38–6.96) 0.87 (0.81–0.94)
≥7 Goldman et al., 200814 849 6 (2–11) 98 (97–99) 2.75 (1.15–6.62) 0.96 (0.92–1.01)
≥8 Goldman et al., 200814 849 2 (0–6) 99 (98–100) 1.69 (0.35–8.02) 0.99 (0.97–1.02)
≥9 Goldman et al., 200814 849 0 (0–5) 100 (99–100) 5.86 (0.12–294.10) 1.00 (0.99–1.01)
=10 Goldman et al., 200814 849 0 (0–5) 100 (99–100) 5.86 (0.12–294.10) 1.00 (0.99–1.01)

Pooled data are reported only when I-square (I2) ≤ 50%.


PAS = Pediatric Appendicitis Score.

Table 10
ED-POCUS in Patients Suspected of Appendicitis

Sample Sensitivity, Specificity,


Studies Size % (95% CI) % (95% CI) LR+ (95% CI) LR–(95% CI)
66
Fox et al., 2007 42 74 (52–90) 85 (60–97) 4.68 (1.61–13.60) 0.31 (0.15–0.63)
Sivitz et al., 201425 264 85 (75–92) 93 (88–96) 11.66 (6.86–19.84) 0.16 (0.10–0.27)
Kim et al., 2015107 115 92 (78–98) 90 (81–96) 9.05 (4.66–17.59) 0.09 (0.03–0.27)
Doniger and Kornblith, 2016110 40 94 (70–100) 88 (68–97) 7.50 (2.58–21.78) 0.07 (0.01–0.48)
Pooled data 461 86 (79–91) 91 (87–94) 9.24 (6.42–13.28) 0.17 (0.09–0.30)

Pooled data are reported only when I-square (I2) ≤ 50%


ED-POCUS = emergency department point-of-care ultrasound.

in all studies. With the exception of three studies (Kent- and PAS in patients suspected of AA are at a high
sis et al.,102 Khanafer et al.,113 Fox et al.106) all trials risk of partial verification bias. Partial verification bias,
failed to specify if the interpreter of the reference test as described by Kohn et al.,116 occurs when the result
(pathologist) was blinded to the results of the index of the index test determines who receives the reference
tests; this can introduce incorporation bias. Incorpora- test. In studies that included only patients suspected
tion bias is likely when the result of the index test can of AA, the index tests (history, physical examination,
determine whether the reference test classifies patients and labs) are already used to decide who enters the
as disease-positive or disease-negative. In several studies study and later receives the reference standard.
the pathologist was solely blinded to the main index Although PAS was not used independently as an
test. For instance, in Schneider et al.,94 Goldman inclusion criterion, the risk of partial verification bias
et al.,14 and Bachur et al.23 the interpreter of the refer- is still high given that PAS is calculated using a combi-
ence test (pathologist) was blinded to the final calculated nation of history, physical examination, and laboratory
PAS but not necessarily to the components of PAS findings. Partial verification bias could inflate estimates
(history, physical examination, and laboratory tests). of sensitivity while underestimating the specificity of
Similarly, in studies by Khan et al.,112 Cayrol et al.,105 index tests.
and Huckins et al.104 pathologist was blinded to the We found all studies at high risk of differential verifi-
main laboratory test studied but not to the history, cation bias. Differential verification bias, also called
physical examination findings, or other laboratory tests “double gold standard bias”, can occur when patients
and in Sivitz et al.,25 pathologist was only blinded to with a positive index test are more likely to receive an
ED-POCUS. immediate reference test whereas those with negative
index test receive only clinical follow-up.116 All trials
Flow and Timing. Studies that examine the accu- used follow-up as an alternate for histopathology in
racy of history, physical examination, laboratory tests, patients undergoing nonsurgical management. Although
540 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

Figure 2. Forest plots—operating characteristics of ED-POCUS. LR = likelihood ratio. [Color figure can be viewed at wileyonlinelibrary.com]

no case of AA was reported in the follow-up group, cases searching electronic records101,113 or contacting patient’s
of self-resolving AA are reported in the literature.117,118 pediatrician,94 the risk of missing AA still exists. Loss to
Furthermore, most included studies did not specify if follow-up, even in small numbers, can introduce signifi-
they discharged any patient on antibiotics, which can cant bias.120,121
result in resolution of milder cases of AA.119 Differential In four studies24,25,106,110 on ED-POCUS, the treating
verification bias can falsely increase the calculated sensi- and the enrolling physician were the same in all or some
tivity and specificity of the index test.116 The risk of bias patients, which introduces differential verification bias
is higher in the study by Huckins et al.104 due to lack of since the results of ED-POCUS could influence further
follow-up or in those studies16,25,94,101,103,106–108,111,113 testing and determine who receives the reference test.
that lost patients to the standard follow-up. Although Sivitz et al.25 reduced this risk by blinding the treating
some of these studies tried alternative follow-up such as physician to the results of ED-POCUS when possible.
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 541

Figure 3. QUADAS-2 assessment of included studies. QUADAS-2 = Quality Assessment Tool for Diagnostic Accuracy Studies. [Color figure
can be viewed at wileyonlinelibrary.com]

Doniger and Kornblith110 and Fox et al.106 decreased reviews. In a review of 26 articles with a total popula-
the risk of differential verification bias by ensuring that tion of 9,356 pediatric patients, Doria et al.122 reported
the treating physician made any decision regarding 94% sensitivity and 95% specificity for CT scan. Moore
diagnosis and treatment approach before performing the et al.123 reviewed 11 studies, encompassing 1,698 pedi-
ED-POCUS. Kim et al.107 did not specify whether their atric patients, and found MRI to be 96.5% sensitive
enrolling and treating physician were the same. and 96.1% specific in diagnosis of AA.
Several studies were at risk of bias due to exclusion We defined Rrx as the risk of mortality and morbid-
of subgroups of their enrolled patients from the final ity following appendectomy. Aziz et al.124 reviewed 23
analysis: Khanafer et al.,113 Bachur et al.,23 Schneider studies with a total population of 6,477 and found the
et al.,94 Wu et al.,108 Zuniga et al.,15 Khan et al.,112 risk of complications, including wound infection, to be
and Escriba et al.16 excluded patients due to incom- 1.5% to 4.9% depending on the technique used (open
plete data or missing data. Fox et al.,106 Mandeville and laparoscopic appendectomy, respectively). In a
et al.,103 Santillanes et al.,111 Wu et al.,108 Escriba review of nine studies with a total population of
et al.,16 and Kim et al.107 excluded patients who were 65,995, Healy et al.125 reported the overall risks of
lost to follow-up from the final analysis, and Kentsis intraabdominal collection formation, wound infection,
et al.102 excluded patients with perforated AA who and readmission to be 2.4, 1.8, and 1.5%, respectively.
underwent interval appendectomy. Based on the literature we estimated Rrx to be 0.05.
We judged the risk of the diagnostic test (Rt) as
Test–Treatment Threshold Estimates 0.00026 for CT scan and zero for MRI. The risk of
We used the method of Pauker and Kassirer31 to estimate CT scan is based on the lifetime risk of radiation-
thresholds for testing or treatment when caring for a pedi- induced cancer following a single abdominal CT scan
atric patient with abdominal pain in the ED. Operative in a 5-year-old (20/100,000 in males and 26/100,000
characteristics for ED-POCUS (Table 10; sensitivity = in females).126
86%, specificity = 91%) were very similar to those of Finally, the Brx of patients with AA has never been,
RUS (sensitivity = 88%, specificity = 94%) reported in nor ever will be, tested by a randomized double-
the literature122 and therefore we decided to remove blinded placebo-controlled methodology; it would be
RUS from our test–treatment threshold model. This unethical to study the spontaneous recovery rate of
model utilizes the unique operating characteristics of each AA without antibiotics or surgery. Without available
diagnostic modality (CT scan and MRI) while controlling evidence we used a conservative estimate for the bene-
for the risk of treatment (Rrx), risks associated with each fit of treating AA (Brx = 0.90).
diagnostic modality (Rt), and the benefit of treatment In the lower half of the Figure 4, the test thresholds
(Brx). Variables are presented as probabilities. are depicted as the left-most open arrow for each diag-
In Figure 4, we created two test–treatment threshold nostic modality (CT scan 0.3% and MRI 0.2%). The
models: 1.CT scan and 2.MRI. The top half of treatment thresholds are represented by the right-most
Figure 4 describes the variables and calculations used open arrow for each diagnostic modality (CT scan
to produce the test and treatment thresholds for CT 46.5% and MRI 60.4%).
and MRI. We used the operating characteristics of CT The vertical dashed lines represent the post-test
scan and MRI documented in recent systematic probabilities of AA in the presence of a negative or a
542 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

positive ED-POCUS. Applying Bayes theorem and Across history and physical examination findings,
using the AA prevalence in patients suspected of AA only cough/hop pain (LR + 7.64) showed high
(42.8%) as the pretest probability, a negative ED- enough LR+ to obviate the need for CT scan (but not
POCUS (LR– = 0.17) would result in a decrease in MRI) in patients with “undifferentiated AA.” How-
the posttest probability from 42.8% to 11% repre- ever, this finding is from a single study and therefore
sented by the left-most vertical dashed line. In case of the results may not be generalizable. No history, physi-
a positive ED-POCUS (LR+ = 9.24), the posttest cal examination, laboratory test, or PAS cutoff point
probability of AA would increase from 42.8% to 87% had a low enough LR– to exclude AA without use of
represented by the right-most vertical dashed line. CT or MRI. In patients suspected of AA, it is inaccu-
As seen in Figure 4, the far right vertical dashed rate to estimate the posttest probability of AA based
line (the probability of AA in presence of a positive on the operating characteristics of history, physical
ED-POCUS, 87%) falls to the right of the treatment examination, laboratory tests, and PAS due to high
threshold for both diagnostic modalities (46.5% for risk of the biases mentioned earlier.
CT scan and 60.4% for MRI). Therefore, in a patient The test–treatment model presented here is an
suspected of AA, a positive ED-POCUS could obviate interactive tool and some variables can be modified in
the need to perform CT scan or MRI and treatment the Microsoft Excel calculator published online (Data
can be initiated. The far left vertical dashed line (the Supplement S2, available as supporting information
probability of AA after a negative ED-POCUS, 11%) in the online version of record of this paper, which is
falls to the right of the test threshold for both CT scan available at http://onlinelibrary.wiley.com/doi/10.1111/
(0.3%) and MRI (0.2%) and, therefore, negative ED- acem.13181/full). For instance, we judged the Rrx to
POCUS is not sufficient to rule out AA without the be 5%. Assigning a greater risk to appendectomy,
need for CT scan or MRI. based on the clinical judgment, will result in an
Based on this model, in patients with undifferenti- increased treatment threshold and therefore additional
ated abdominal pain (pretest probability of 13.4%) a testing may be needed.
test needs to have LR+ > 5.8 and LR+ > 11 to estab-
lish the diagnosis of AA without the need for CT and
DISCUSSION
MRI, respectively. In the same population, a test with
LR– < 0.03 can rule out AA obviating the need for Our systematic review examined the utility of history,
CT and MRI (posttest probability = 0%). physical examination, laboratory results, PAS, and ED-

Figure 4. Test–treatment threshold model.


ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 543

POCUS for the diagnosis of AA in ED pediatric pain and 19 studies15,16,23–25,94,101–108,110–114 on


patients. Twenty-one studies met the inclusion criteria patients suspected of AA.
with most studies dedicated to evaluating history and Studies that used either “suspected appendicitis” or
physical examination, laboratory tests, and PAS at “RLQ abdominal pain” as their inclusion criteria are at
high risk of bias. We found no single history, physical high risk of partial verification bias given that the index
examination, laboratory test finding, or PAS cutoff tests (history and physical exam findings) were already
point to be sufficiently robust enough to rule out AA used as part of their inclusion criteria. The same logic
and eliminate the need for using CT scan or MRI. applies to PAS studies that used patients “suspected of
This is not to imply that history, physical examination, appendicitis” as their inception cohort. Partial verifica-
or laboratory tests are not valuable in the diagnosis of tion bias falsely increases sensitivity and decreases speci-
AA as the presence of these findings is necessary to ficity and therefore alters the calculated LRs.
suspect AA in a patient presenting to the ED with Studies on patients with undifferentiated abdominal
abdominal pain. pain may provide less biased estimates of the operat-
Compared to the two previously published system- ing characteristics of history and physical examination
atic reviews on pediatric AA by Bundy et al.7 and findings. Comparing the test characteristics of cough/
Dahabreh et al.,26 we used more rigorous inclusion/ hop pain from the study by Goldman et al.14 study
exclusion criteria and included only prospective studies (N = 849), which included patients with undifferenti-
dedicated to ED patients. Although reviews such as ated abdominal pain to studies on patients suspected
those by Bundy et al.7 and Dahabreh et al.26 are more of AA (five studies, N = 1,935), demonstrates the
comprehensive and provide the reader with a sum- effect of partial verification bias. For this variable, LR+
mary of all available literature on pediatric AA, their is lower (1.61 vs 7.46) and LR– is higher (0.52 vs
results cannot be used to answer our clinical question: 0.31) in suspected of AA studies compared to Gold-
Which element(s) of history, physical examination, lab- man et al.14 on undifferentiated abdominal pain.
oratory tests, or imaging studies in ED pediatric Unfortunately, few studies are available on patients
patients could rule in/out AA obviating the need for with undifferentiated abdominal pain.
CT and MRI? In a cohort of patients with undifferentiated abdom-
Our results were in concordance with Dahabreh inal pain, Goldman et al.14 found the presence of
et al.,26 who also found history, physical examination, cough/hop pain and “pain migration to RLQ” to be
and laboratory test findings to have “relatively low” most suggestive of AA (LR+ = 7.64 and LR+ = 4.81,
sensitivity and specificity when used in isolation. respectively). Using our test–treatment model, in
Bundy et al.7 found history of fever to be “the most patients with undifferentiated abdominal pain (pretest
useful” but not diagnostic finding associated with probability of AA = 13.4%), presence of cough/hop
AA. Although Bundy et al. reviewed five studies for pain (LR+ = 7.64) could obviate the need for CT scan
the variable fever, they derived their conclusion from but not MRI (posttest probability of AA = 54% com-
only a single study on undifferentiated abdominal pared to the treatment threshold of 46.5% for CT
pain patients (O’Shea et al.109) also included in our scan and 60.4% for MRI). However, this finding
review. Our review does not support statement by should be interpreted with caution as it is derived
Bundy et al. about fever. In patients with undifferen- from one single-center study and therefore may not be
tiated abdominal pain, using the pretest probability generalizable.
of 9.8% (AA prevalence in O’Shea et al.109) and One approach used to increase the power of his-
applying Bayes theorem, history of fever increases the tory, physical examination, and laboratory tests in diag-
probability of AA to only 27%, which is below the nosing AA is to combine them into a scoring system.
treatment threshold for both CT (46.5%) and MRI One of the most studied of these scoring systems is
(60.4%). PAS, which we used as an example to evaluate the
One criticism of previous systematic reviews7,26 is bias and heterogeneity in validation studies. PAS was
pooling of data from studies with different inclusion developed by Samuel12 as a clinical decision rule to
criteria. In an attempt to compare studies with similar identify high-risk patients for AA (Table 11). In a
inclusion methodology, we separated our reviewed prospective single-center study, Samuel12 evaluated
studies into two groups: Goldman et al.14 and O’Shea 1,170 patients with a very high AA prevalence of 63%
et al.109 on patients with undifferentiated abdominal and suggested PAS ≥ 6 as a good predictor of AA
544 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

and reported a sensitivity of 100% and specificity of Khanafer et al.113) for a total of eight studies
92%. However, numerous studies aiming to validate (N = 4,128). One criticism to the review by Ebell and
PAS have not found such favorable operating charac- Shinholser127 is inappropriately pooling of the data
teristics.94,103,113 Moreover, studies that aim to validate from studies with different inclusion criteria and
PAS in a cohort of patients suspected of AA are at heterogeneous results128 (I2 = 91%–96%). Although
considerable risk of partial verification bias. Patients we grouped studies with similar inclusion criteria
suspected of AA are more likely to be positive for together, we still observed heterogeneous results for
many variables of PAS (Table 11) and consequently most cutoff points of PAS (I2 = 75%–94%). Even
assigned a higher final score. The use of the operating studies with similar settings and AA prevalences had
characteristics of PAS, derived from a series of studies heterogeneous results. We unsuccessfully attempted to
with such bias and their reapplication on patients sus- contact the authors of the included studies to utilize
pected of AA, substantially increases the risk of bias. their raw data to calculate interval LRs instead of using
A similar logic applies to any other scoring arbitrary cutoff point and therefore decrease hetero-
system13,93,95,98 derived and validated on patients sus- geneity.
pected of AA. Studies on patients with undifferenti- One possible explanation for high heterogeneity
ated abdominal pain are at lower risk of such bias. observed across PAS studies is that six of eight vari-
We could only find one study that met our inclu- ables composing the PAS are history and physical
sion criteria and tested PAS in patients with undif- examination findings and therefore examiner-depen-
ferentiated abdominal pain and thus at lower risk of dent. In one recent study focusing solely on the
partial verification bias. Goldman et al.14 suggested interexaminer reliability of history and physical exami-
PAS ≥ 7 to be diagnostic of AA and PAS ≤ 2 to nation findings in pediatric abdominal pain patients
have high validity for ruling out AA. However, with and without AA,129 only vomiting showed high
using the data from Goldman et al.14 (pretest proba- interexaminer reliability (j = 0.82) with other findings
bility of 14.5%) and applying Bayes theorem, in failing to show acceptable interexaminer reliabilities
patients with undifferentiated abdominal pain and (j = 0.14–0.54). Yen et al.130 also found poor interex-
PAS ≥ 7, the posttest probability of AA would aminer reliability of physical examination findings in
increase to only 32%, which is lower than the treat- pediatric patients with abdominal pain (j = 0.13–
ment threshold for both CT scan (46.5%) and MRI 0.54). When most components of a clinical score are
(60.4%). In the same population but with PAS ≤ 2, inherently at risk of low reproducibility, it is only natu-
the posttest probability of AA would decrease to ral for the end results to be heterogeneous as well.
7%, which is above the test threshold for both CT Observing the high heterogeneity and poor opera-
scan (0.3%) and MRI (0.2%). Therefore, neither ting characteristics of history, physical examination,
PAS ≥ 7 nor PAS ≤ 2 can eliminate the need for laboratory tests, and PAS, we decided to investigate
CT scan or MRI. According to our test–treatment the operating characteristics of ED-POCUS. Test char-
model, only PAS = 0 decreases the posttest probabil- acteristics of ED-POCUS were similar to those of
ity of AA low enough to obviate the need for CT RUS as reported by Doria et al.122 (sensitivity = 86%
or MRI. In other words, if a patient with undiffer- vs. 88% and specificity = 91% vs. 94%). Therefore,
entiated abdominal pain is negative for all
variables of PAS, the probability of AA is nearly
0% and the patient can be discharged without fur- Table 11
ther investigation. Variable of Pediatric Appendicitis Score (PAS)

Overall we found very heterogeneous results for


Variable Point Value
most cutoff points of PAS. Our results are similar to
Migration of pain 1
those of Ebell and Shinholser.127 In a systematic Anorexia 1
review of six studies, Ebell and Shinholser127 did not Nausea/vomiting 1
RLQ tenderness 2
find any cutoff point that can rule in or rule out AA. Pain with cough/hopping/percussion 2
Of articles reviewed by Ebell and Shinholser,127 five Fever
Leukocytosis
1
1
were included in our review along with three addi- Differential WBC count with a left shift 1
tional studies that were not reviewed by Ebell and
PAS = Pediatric Appendicitis Score.
Shinholser127 (Wu et al.,108 Bachur et al.,23 and
ACADEMIC EMERGENCY MEDICINE • May 2017, Vol. 24, No. 5 • www.aemj.org 545

we decided not to include RUS in our test–treatment In one RCT in children, Svensson et al.131 treated
threshold model. 24 pediatric patients suspected of AA with antibiotics
Using our test–treatment threshold model (Fig- alone while 26 were sent to surgery. During the
ure 4) in patients suspected of AA (pretest probabil- follow-up period of 1 year, two patients (8%)
ity of 42.8%) and a positive ED-POCUS, the had appendectomy with pathologically proven AA.
physician can assume the diagnosis of AA (posttest This is similar to the recurrence rate in antibiotic ther-
probability of 87%) without the need for CT scan apy in pediatric patients with complicated AA with or
or MRI. A negative ED-POCUS decreases the postt- without interval appendectomy.135 Based on the litera-
est probability of AA from 42.8% to 11% exceeding ture,131–133,136–138 we hypothesized the risk of antibio-
the testing threshold for CT (0.3%) and MRI tic treatment failure to be 10 to 20 percent. Therefore,
(0.2%), and further investigation is recommended. the risk of recurrence in ED-POCUS–negative patients
The low testing threshold of CT scan and MRI can discharged on antibiotics will be 1% to 2%. This is a
be attributed to a combination of high benefit of rough estimate considering that most trials on treating
treatment, low risk associated with these diagnostic AA patients with antibiotics are not RCTs and, there-
modalities, and the low complication rate of appen- fore, at substantial risk of selection bias. Whether or
dectomy. In fact, to obviate the need for CT and not to accept the risk of treatment failure depends on
MRI using ED-POCUS, the pretest probability must physician’s clinical judgment and the setting in which
be lower than 2.8%, which is extremely unlikely in patient is being treated. If patient can be followed and
a patient evaluated for abdominal pain “suspected of transferred to a hospital in case of a recurrence, 1% to
AA”. Factors such as availability of radiology modali- 2% may be a reasonable risk to accept. However, if
ties, cost of treatment, and length of stay undeniably the treating physician has high clinical suspicion for
play important roles in a real-life setting. However, AA despite negative ED-POCUS or anticipates poor
such factors are beyond the scope of this review medication compliance or loss to follow-up, using CT
and are not accounted for within the aforemen- scan or MRI to make the final diagnosis may be a
tioned calculations. better approach.
In a patient with negative ED-POCUS, the decision
to use further imaging studies, observe in the ED,
obtain surgical consultation, or discharge to home is LIMITATIONS
based on treating physician’s clinical judgment. An We excluded all studies in languages other than Eng-
alternative management approach to performing CT lish, which can decrease the generalizability of the
or MRI in patients with negative ED-POCUS could findings. We did not have access to patient-level data;
be antibiotic therapy. While nonoperative manage- therefore, it was impossible to evaluate the effect of
ment of AA is not the main focus of this review, we factors such as severity of the disease, ethnicity, or
briefly address it here given the increasing evidence socioeconomics. All studies on ED-POCUS included
supporting this approach. Antibiotic therapy is a com- in this review were performed in academic settings
mon practice in pediatric patients with complicated decreasing the generalizability of the results to other
AA but less studied in uncomplicated AA. Few stud- settings.
ies on this subject131–133 demonstrated no difference
in the rate of postoperative complications between
children who underwent appendectomy after failure of CONCLUSIONS
antibiotic therapy and those who were treated surgi-
While the aim of this review is not to provide a prac-
cally upon first presentation of AA. This is similar to
tice guideline, the results can be used by physicians to
the findings from the adult population. In a system-
make decisions in the ED when caring for a child
atic review of five randomized controlled trials (RCTs)
with abdominal pain. The following is the summary
in adult patients with uncomplicated AA, Rollins
of our findings:
et al.134 showed that risk of complications was lower
in those who had appendectomy following “failure” of • In patients presenting to the ED with undifferenti-
antibiotic therapy compared to those who underwent ated abdominal pain, migration of pain to the right
appendectomy upon their first presentation (10.9% vs lower quadrant or presence of cough/hop pain in
17.9%). physical examination increases the probability of
546 Benabbas et al. • DIAGNOSING ACUTE APPENDICITIS IN CHILDREN IN THE ED

acute appendicitis. Once acute appendicitis is sus- 3. Becker T, Kharbanda A, Bachur R. Atypical clinical features
pected, no single history, physical examination, lab- of pediatric appendicitis. Acad Emerg Med 2007;14:124–9.
oratory finding, or Pediatric Appendicitis Score 4. Nance ML, Adamson WT, Hedrick HL. Appendicitis in
result can confirm the diagnosis without the need the young child: a continuing diagnostic challenge. Pedi-
atr Emerg Care 2000;16:160–2.
for imaging studies.
• The pooled operating characteristics for ED point-
5. Davenport M. Acute abdominal pain in children. BMJ
1996;312:498–501.
of-care ultrasound in this review are similar to
6. Marzuillo P, Germani C, Krauss BS, Barbi E. Appendici-
those reported for radiology department ultrasound tis in children less than five years old: a challenge for the
in the literature. If the operator of ED point-of-care general practitioner. World J Clin Pediatr 2015;4:19–24.
ultrasound has similar expertise and training as 7. Bundy DG, Byerley JS, Liles EA, Perrin EM, Katznelson
operators in our included studies, ED point-of-care J, Rice HE. Does this child have appendicitis? JAMA
ultrasound can replace radiology department ultra- 2007;298:438–51.
sound for the diagnosis of acute appendicitis. 8. Bratton SL, Haberkern CM, Waldhausen JH. Acute
• In a pediatric patient suspected of acute appen- appendicitis risks of complications: age and Medicaid
dicitis, a positive ED point-of-care ultrasound is insurance. Pediatrics 2000;106:75–8.
diagnostic. However, a negative ED point-of-care 9. Peng YS, Lee HC, Yeung CY, Sheu JC, Wang NL, Tsai
ultrasound is not sufficient to rule out acute appen- YH. Clinical criteria for diagnosing perforated appendix in
pediatric patients. Pediatr Emerg Care 2006;22:475–9.
dicitis without the use of computed tomography
10. Narsule CK, Kahle EJ, Kim DS, Anderson AC, Luks FI.
scan or magnetic resonance imaging.
Effect of delay in presentation on rate of perforation in
children with appendicitis. Am J Emerg Med
Areas of Future Research 2011;29:890–3.
Clinical scores are perhaps more valuable if 11. Rothrock SG, Pagane J. Acute appendicitis in children:
constructed using variables that are well studied in emergency department diagnosis and management. Ann
multiple settings and with a design that is less prone Emerg Med 2000;36:39–51.
to partial verification bias. A multicenter study on 12. Samuel M. Pediatric Appendicitis Score. J Pediatr Surg
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very beneficial in developing future clinical scores or stephen W, Langer JC. Prospective validation of the Pedi-
atric Appendicitis Score. J Pediatr 2008;153:278–82.
guidelines. To decrease the risk of differential verifica-
15. Zuniga RV, Arribas JL, Montes SP, et al. Application of
tion bias, it is suggested that in future studies patients
Pediatric Appendicitis Score on the emergency depart-
observed without surgery undergo a complete follow-
ment of a secondary level hospital. Pediatr Emerg Care
up. Also, the operating characteristics and interrater 2012;28:489–92.
reliability of ED point-of-care ultrasound should be 16. Escriba A, Gamell AM, Fernandez Y, Quintilla JM,
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sification for the diagnosis of acute appendicitis. Pediatr
The authors thank Christopher Stewart, senior assistant librarian Emerg Care 2011;27:165–9.
at SUNY Downstate Medical Center, for his help in formulating 17. Bhatt M, Joseph L, Ducharme FM, Dougherty G, McGil-
the literature searches. livray D. Prospective validation of the Pediatric Appen-
dicitis Score in a Canadian pediatric emergency
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Surg 2014;219:272–9. 858/full
Data Supplement S1. Search strategies and MeSH
Supporting Information terms used.
Data Supplement S2. Test–treatment threshold
The following supporting information is available in model.
the online version of this paper available at http://

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