Clinical Policy: Critical Issues in the Evaluation and Management of Emergency Department Patients With Suspected Appendicitis

Article Outline

• Abstract
• Introduction
• Methodology
  • Level A recommendations
  • Level B recommendations
  • Level C recommendations
  • Scope of Application
  • Inclusion Criteria
  • Exclusion Criteria
• Critical Questions
  • Patient Management Recommendations
    • Level A recommendations
    • Level B recommendations
    • Level C recommendations
• Patient Management Recommendations
  • Level A recommendations
  • Level B recommendations
  • Level C recommendations
• Patient Management Recommendations
  • Level A recommendations
  • Level B recommendations
  • Level C recommendations
  • Future Areas of Research
• Acknowledgment
• Appendix
• References
• Copyright

Members of the American College of Emergency Physicians Clinical Policies Committee (Oversight Committee):

Wyatt W. Decker, MD (Co-Chair 2006-2007, Chair 2007-2009)

Andy S. Jagoda, MD (Chair 2003-2006, Co-Chair 2006-2007)

Deborah B. Diercks, MD

Barry M. Diner, MD (Methodologist)

Jonathan A. Edlow, MD

Francis M. Fesmire, MD

John T. Finnell, II, MD, MSc (Liaison for Emergency Medical Informatics Section 2004-2006)

Steven A. Godwin, MD

Sigrid A. Hahn, MD

Benjamin W. Hatten, MD (EMRA Representative 2008-2009)

John M. Howell, MD

J. Stephen Huff, MD

Eric J. Lavonas, MD

Thomas W. Lukens, MD, PhD

Sharon E. Mace, MD

Donna L. Mason, RN, MS, CEN (ENA Representative 2004-2006)

Edward Melnick, MD (EMRA Representative 2007-2008)

Anthony M. Napoli, MD (EMRA Representative 2004-2006)

Devorah J. Nazarian, MD

AnnMarie Papa, RN, MSN, CEN, FAEN (ENA Representative 2007-2009)

Jim Richmann, RN, BS, MA(c), CEN (ENA Representative 2006-2007)

Scott M. Silvers, MD

Edward P. Sloan, MD, MPH

Molly E. W. Thiessen, MD (EMRA Representative 2006-2008)

Robert L. Wears, MD, MS (Methodologist)

Stephen J. Wolf, MD

Cherri D. Hobgood, MD (Board Liaison 2004-2006)

David C. Seaberg, MD, CPE (Board Liaison 2006-2009)

Rhonda R. Whitson, RHIA, Staff Liaison, Clinical Policies Committee and Subcommittees

[Ann Emerg Med. 2010;55:71-116.]

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Abstract 

This clinical policy from the American College of Emergency Physicians is an update of a 2000 clinical policy on the evaluation and management of patients presenting with nontraumatic acute abdominal pain.¹ A writing subcommittee reviewed the literature to derive evidence-based recommendations to help clinicians answer the following critical questions: (1) Can clinical findings be used to guide decisionmaking in the risk stratification of patients with possible appendicitis? (2) In adult patients with suspected acute appendicitis who are undergoing a computed tomography scan, what is the role of contrast? (3) In children with suspected acute appendicitis who undergo diagnostic imaging, what are the roles of computed tomography and ultrasound in diagnosing acute appendicitis? Evidence was graded and recommendations were given based on the strength of the available data in the medical literature.

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Introduction 

Abdominal pain is a high-volume, high-risk chief complaint. In 2005, patients with abdominal pain composed 6.8% of 115 million annual emergency department (ED) visits.² Ten percent of closed malpractice claims for emergency physicians involve the missed diagnosis of abdominal pain.³ Among children between 6 and 17 years of age, appendicitis is the second most common cause of malpractice litigation against emergency physicians.⁴ The diagnosis of appendicitis can be challenging even in the most experienced of clinical hands.

Despite the increasing utilization of computed tomography (CT) in patients with possible appendicitis, such widespread use may be unnecessary. Clinical indicators (eg, signs, symptoms, laboratory tests) exist that might identify patients who require abdominal CT to diagnose acute appendicitis. Such indicators could facilitate the early identification of ED patients who do and do not require CT, but are such strategies effective?

Once the decision is made to image, performing a CT may or may not involve the use of contrast. If contrast is used, does it increase diagnostic performance in a clinically meaningful way? In children, some clinicians use ultrasound before or in lieu of CT to diagnose appendicitis. Although ultrasound does not involve ionizing radiation or the risks associated with contrast, the accuracy of either a positive or negative ultrasound result merits discussion.

Not every patient with possible appendicitis needs abdominal imaging. Although this clinical policy addresses diagnostic studies for appendicitis, not all patients with possible appendicitis require diagnostic tests. For example, patients with very low clinical suspicion for appendicitis may be discharged with minimal or no testing. Similarly, patients with high clinical suspicion for appendicitis may be referred to a surgeon, with minimal or no testing.⁵ If the clinical presentation warrants, a surgical consultant should be notified as early as is clinically warranted.

This clinical policy addresses evidence-based questions framed around these issues. Rather than approach the topic of abdominal pain in its entirety, this policy's scope is limited to 3 questions:

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Methodology 

This clinical policy was created after careful review and critical analysis of the medical literature. Multiple searches of MEDLINE and the Cochrane database were performed. Specific key words/phrases used in the searches are identified under each critical question. To update the 2000 American College of Emergency Physicians (ACEP) policy, all searches were limited to English-language sources, human studies, and to articles published from January 2000 to March 2007. Additional articles were reviewed from the bibliography of articles cited and from published textbooks and review articles. Subcommittee members supplied articles from their own files, and more recent articles identified during the process were also included.

The reasons for developing clinical policies in emergency medicine and the approaches used in their development have been enumerated.⁶ This policy is a product of the ACEP clinical policy development process, including expert review, and is based on the existing literature; when literature was not available, consensus of emergency physicians was used. Expert review comments were received from individual emergency physicians and from individual members of the American Academy of Pediatrics, the American College of Radiology, the Society for Academic Emergency Medicine, the Society for Pediatric Radiology, ACEP's Pediatric Emergency Medicine Section, and ACEP's Emergency Ultrasound Section. Their responses were used to further refine and enhance this policy; however, their responses do not imply endorsement of this clinical policy. Clinical policies are scheduled for revision every 3 years; however, interim reviews are conducted when technology or the practice environment changes significantly.

All articles used in the formulation of this clinical policy were graded by at least 2 subcommittee members for strength of evidence and classified by the subcommittee members into 3 classes of evidence on the basis of the design of the study, with design 1 representing the strongest evidence and design 3 representing the weakest evidence for therapeutic, diagnostic, and prognostic clinical reports, respectively (Appendix A). Articles were then graded on 6 dimensions thought to be most relevant to the development of a clinical guideline: blinded versus nonblinded outcome assessment, blinded or randomized allocation, direct or indirect outcome measures (reliability and validity), biases (eg, selection, detection, transfer), external validity (ie, generalizability), and sufficient sample size. Articles received a final grade (Class I, II, III) on the basis of a predetermined formula, taking into account design and quality of study (Appendix B). Articles with fatal flaws were given an “X” grade and not used in formulating recommendations in this policy. Evidence grading was done with respect to the specific data being extracted and the specific critical question being reviewed. Thus, the level of evidence for any one study may vary according to the question, and it is possible for a single article to receive different levels of grading as different critical questions are answered. Question-specific level of evidence grading may be found in the Evidentiary Table included at the end of this policy.

Clinical findings and strength of recommendations regarding patient management were then made according to the following criteria:

Level A recommendations 

Generally accepted principles for patient management that reflect a high degree of clinical certainty (ie, based on strength of evidence Class I or overwhelming evidence from strength of evidence Class II studies that directly address all of the issues).

Level B recommendations 

Recommendations for patient management that may identify a particular strategy or range of management strategies that reflect moderate clinical certainty (ie, based on strength of evidence Class II studies that directly address the issue, decision analysis that directly addresses the issue, or strong consensus of strength of evidence Class III studies).

Level C recommendations 

Other strategies for patient management that are based on preliminary, inconclusive, or conflicting evidence, or in the absence of any published literature, based on panel consensus.

There are certain circumstances in which the recommendations stemming from a body of evidence should not be rated as highly as the individual studies on which they are based. Factors such as heterogeneity of results, uncertainty about effect magnitude and consequences, strength of prior beliefs, and publication bias, among others, might lead to such a downgrading of recommendations.

When possible, clinically oriented statistics (ie, likelihood ratios, odds ratios, risk ratios, and number needed to treat) will be presented to help the reader better understand how the results can be used with the patient and will be given priority over simple descriptive statistics (eg, sensitivity, specificity, and predictive values). The former allow the reader to interpret study results taking into consideration probability of disease. For a more thorough explanation of these statistical methodologies, see Appendix C.

This policy is not intended to be a complete manual on the evaluation and management of patients with nontraumatic acute abdominal pain but rather a focused examination of critical issues that have particular relevance to the current practice of emergency medicine.

It is the goal of the Clinical Policies Committee to provide an evidence-based recommendation when the medical literature provides enough quality information to answer a critical question. When the medical literature does not contain enough quality information to answer a critical question, the members of the Clinical Policies Committee believe that it is equally important to alert emergency physicians to this fact.

Recommendations offered in this policy are not intended to represent the only diagnostic and management options that the emergency physician should consider. ACEP clearly recognizes the importance of the individual physician's judgment. Rather, this guideline defines for the physician those strategies for which medical literature exists to provide support for answers to the crucial questions addressed in this policy.

Scope of Application 

This guideline is intended for physicians working in hospital-based EDs.

Inclusion Criteria 

This guideline is intended for patients presenting to the ED with acute, nontraumatic abdominal pain and possible or suspected appendicitis.

Exclusion Criteria 

This guideline is not intended to address the care of patients with trauma-related abdominal pain, or pregnant patients.

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Critical Questions 

1. Can clinical findings be used to guide decisionmaking in the risk stratification of patients with possible appendicitis?

Patient Management Recommendations 

None specified.

In patients with suspected acute appendicitis, use clinical findings (ie, signs and symptoms) to risk-stratify patients and guide decisions about further testing (eg, no further testing, laboratory tests, and/or imaging studies), and management (eg, discharge, observation, and/or surgical consultation).

None specified.

Key words/phrases for literature searches: appendicitis, abdominal pain, clinical indicators, clinical predictors, prediction rule, probability, sensitivity and specificity or predictive value of tests or ROC curve, diagnosis, differential, decisionmaking, decision support techniques, diagnostic errors, missed diagnoses, computed tomography, and variations and combinations of the key words/phrases.

Whereas the diagnosis of appendicitis is often straightforward, many patients present with early or atypical signs and symptoms. Further, laboratory test results may be normal in the setting of appendicitis. We reviewed the literature to determine which clinical findings, if any, risk-stratify patients with suspected appendicitis and suggest the need for either a radiologic procedure or surgery.

For the purposes of this publication, missed appendicitis is considered a false-negative clinical evaluation, and the removal of a normal appendix is considered a false-positive clinical evaluation.

History and Physical Examination

In a meta-analysis of approximately 4,000 patients (Class II), right lower quadrant abdominal pain was the most useful clinical finding in suspected appendicitis (positive likelihood ratio 95% confidence interval [CI] 7.31 to 8.46 and a negative likelihood ratio 95% CI 0 to 0.28).⁷ The authors only reported 95% CI because the included studies were heterogeneous.⁷ In a separate meta-analysis, Andersson⁸ found that pain migration (positive likelihood ratio 2.06, 95% CI 1.63 to 2.60; and negative likelihood ratio 0.42, 95% CI 0.40 to 0.69) and pain progression (positive likelihood ratio 1.39, 95% CI 1.29 to 1.50; and negative likelihood ratio 0.46, 95% CI 0.27 to 0.77) were less helpful. Two Class III studies found that right lower quadrant tenderness had positive likelihood ratios of 2.3 and 1.1 and negative likelihood ratios of 0 and 0.1.⁹, ¹⁰ Rigidity on abdominal examination carried a positive likelihood ratio of 3.8. Anorexia, tenderness on rectal examination, guarding, fever, and percussion tenderness in the right lower quadrant all had positive likelihood ratios below 2.9.⁷, ⁸

Laboratory Tests

Although the total WBC count is frequently used in the diagnostic evaluation of acute appendicitis, when used alone it is not a consistent predictor. Cardall et al¹¹ demonstrated a positive likelihood ratio for an elevated WBC count (>10,000/mm³) of 1.59 and a negative likelihood ratio of 0.46. In the meta-analysis by Andersson,⁸ the positive likelihood ratio of an elevated WBC count (>10,000/mm³) for appendicitis was 2.47 (95% CI 2.06 to 2.95) and the negative likelihood ratio was 0.25 (95% CI 0.18 to 0.36). The positive likelihood ratio was 3.47 (95% CI 1.6 to 7.8) in those patients with a WBC count greater than 15,000/mm³.⁸

In a Class III study, Kessler et al¹² found that an elevated WBC count (>10,000/mm³) carried a positive likelihood ratio of 2.7 and a negative likelihood ratio of 0.5. Birchley¹³ found similar results when evaluating the WBC count in a small single-surgeon series.

Whereas neither the WBC count nor the C-reactive protein level consistently diagnoses or excludes appendicitis when used alone, the combination of C-reactive protein and WBC count is more helpful.⁸ For a C-reactive protein level of 10 mg/L, Andersson⁸ identified a positive likelihood ratio of 4.24 (95% CI 1.16 to 15.53) and a negative likelihood ratio of 0.11 (95% CI 0.05 to 0.25) for acute appendicitis. However, in this same meta-analysis, the negative likelihood ratio for the combination of a WBC count of 10,000/mm³ and a C-reactive protein of 8 mg/L was 0.03 (95% CI 0.0 to 0.14). The positive likelihood ratio for the combination of both of these laboratory results was 23.32 (95% CI 6.87 to 84.79).

The Alvarado Score

Combining various signs and symptoms into a scoring system may be more useful in predicting the presence or absence of appendicitis. The Alvarado score, originally described in 1986, is the most widely reported scoring system for acute appendicitis¹⁴ (Table 1). The score was developed retrospectively from patients hospitalized with suspected appendicitis. The Alvarado score combines patient symptoms, physical examination results, and laboratory values to assign a score from 0 to 10.

Table 1. Alvarado score in acute appendicitis.

Adapted from Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med. 1986;15:557-564 with permission from Elsevier.

Theoretically, higher Alvarado scores are associated with a higher likelihood of appendicitis and lower scores with a lower likelihood of appendicitis. Whether the Alvarado score can reliably predict the need for CT is debatable. In a Class III study, McKay and Shepherd¹⁵ reviewed 150 charts to develop guidelines for CT scanning based on Alvarado scoring. Five percent of patients with scores of 3 or less had appendicitis, 36% of patients with scores between 4 and 6 had appendicitis, and 78% of patients with scores of 7 or higher had appendicitis. The authors concluded that patients with scores of 3 or less should not have CT (2 patients with appendicitis would have been missed in their series), those with scores between 4 and 6 should have CT, and those with scores 7 or higher would benefit from surgical consultation before CT. Chan et al,¹⁶ in a Class III study, found that no patients with Alvarado scores below 5 had appendicitis.

In 2 other studies, a low Alvarado score did not reliably exclude appendicitis or the need for CT. In a Class III study, Gwynn⁹ found that 12 (8.4%) of 143 subjects with appendicitis had Alvarado scores below 5. Patients in extremes of age (60 to 80 and 0 to 10 years of age) were misdiagnosed more frequently. In a small Class III study, Yildirim et al¹⁷ found that 72% of patients with Alvarado scores between 1 and 4 ultimately had appendicitis, according to CT results and subsequent surgery. The authors recommended imaging even patients with low Alvarado scores.

Pediatric Considerations

In a Class II prospective cohort study, Kharbanda et al¹⁸ identified 5 historical, physical examination, and laboratory findings that are significantly associated with pediatric appendicitis. The authors used logistic regression to identify nausea, a history of focal right lower quadrant pain, difficulty walking, rebound tenderness, and an absolute neutrophil count of greater than 6,750/mm³ as significantly associated with acute appendicitis.¹⁸ When these variables were combined into a scoring system and applied to a validation cohort, the scoring system resulted in a negative likelihood ratio of 0.058 (95% CI 0.008 to 0.41).

In a Class III study, Wang et al¹⁹ evaluated the diagnostic performance of selected blood tests in children presenting to the ED with possible appendicitis. The authors defined an elevated WBC count and a left shift based on age-defined normal values. For both an elevated WBC count and a left shift, the positive likelihood ratio was 9.8. For either an elevated WBC count or a left shift, the negative likelihood ratio was 0.26. In contrast, the diagnostic performances of an elevated WBC count (positive likelihood ratio 3.4; negative likelihood ratio 0.41) and a left shift (positive likelihood ratio 5.9; negative likelihood ratio 0.45) individually were not as strong. The authors of this study did not disclose a criterion standard for the diagnosis or exclusion of acute appendicitis.

In a Class III prospective study, van den Broek et al²⁰ found that temperature greater than 38°C, a WBC count of 10,100/mm³ or greater, and rebound tenderness were significantly associated with pediatric appendicitis. Using these factors in a scoring system, they created a prediction rule that resulted in a 1% missed appendicitis rate and a 9% negative appendectomy rate.

In a retrospective study, Klein et al²¹ identified guarding and temperature greater than 38.4°C as predictive of appendicitis in girls 5 to 12 years of age, and tenderness and vomiting as predictive in boys 5 to 12 years of age. In boys older than 12 years, guarding and anorexia were predictive of appendicitis. In contrast to the studies by Kharbanda et al¹⁸ and van den Broek et al,²⁰ Klein et al²¹ found that adding WBC count to other clinical factors decreased diagnostic performance.

2. In adult patients with suspected acute appendicitis who are undergoing a CT scan, what is the role of contrast?

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Patient Management Recommendations 

Level A recommendations 

None specified.

Level B recommendations 

In adult patients undergoing a CT scan for suspected appendicitis, perform abdominal and pelvic CT scan with or without contrast (intravenous [IV], oral, or rectal). The addition of IV and oral contrast may increase the sensitivity of the CT scan for the diagnosis of appendicitis.

Level C recommendations 

None specified.

Key words/phrases for literature searches: appendicitis, computed tomography, contrast, diagnosis, sensitivity, specificity, and variations and combinations of the key words/phrases.

Performing abdominal and pelvic CT without enteric or IV contrast for the evaluation of patients with suspected acute appendicitis is appealing for its speed and simplicity. Whether contrast provides a diagnostic advantage has been debated. IV contrast highlights inflammation in the wall of the appendix and in the tissue around the appendix.²², ²³ Enteric contrast helps differentiate the appendix from surrounding structures.²⁴, ²⁵ Enteric and IV contrast may be more helpful in thin patients with low body mass index who lack sufficient mesenteric fat to demonstrate periappendiceal fat stranding that is associated with appendicitis.²⁶, ²⁷, ²⁸ Enteric and IV contrast also help identify conditions other than acute appendicitis (eg, diverticulitis, inflammatory bowel disease, cancer).²², ²⁹, ³⁰

Contrast has disadvantages. Oral contrast requires time to administer, requires time to transit the bowel, and may be difficult to tolerate for patients with abdominal pain and vomiting. Rectal contrast requires less time to administer than oral contrast but may be uncomfortable and unpleasant. IV contrast may lead to serious allergic reactions and renal failure. Contrast also adds to cost.³¹ Increased sensitivity of newer-generation multislice CT scanners may improve diagnostic accuracy, obviating the need for contrast.

Multiple investigators have studied CT of the abdomen and pelvis for the evaluation of acute appendicitis (Table 2). Most of these studies evaluate a single CT technique (eg, noncontrast CT, CT with oral contrast, CT with rectal contrast, CT with IV contrast, CT with some combination of contrast types). In the majority of these studies, CT performs reasonably well, regardless of whether or not contrast is used.²², ²⁶, ²⁷, ³¹, ³², ³³, ³⁴, ³⁵, ³⁶, ³⁷, ³⁸, ³⁹, ⁴⁰, ⁴¹, ⁴², ⁴³, ⁴⁴, ⁴⁵, ⁴⁶, ⁴⁷, ⁴⁸, ⁴⁹ When these studies are compared, it appears that the improvement in diagnostic accuracy achieved by the addition of IV or enteric contrast is small.

Table 2. Diagnostic accuracy of CT for diagnosing acute appendicitis in adults.

Pts, patients; LR, likelihood ratio.

To determine the utility of oral contrast, Anderson et al⁵⁰ performed a systematic review of 23 prospective and retrospective reports on CT for suspected appendicitis. They reported the following weighted sensitivities and specificities: noncontrast CT 93% and 98%, CT with oral and IV contrast 93% and 93%, and CT with rectal contrast 97% and 97%. The authors concluded that oral contrast does not improve the accuracy of CT for the diagnosis of acute appendicitis.

The majority of publications concerning CT for the evaluation of acute appendicitis report on a single CT technique. Comparing the available studies of individual CT techniques is problematic. Study design varies significantly among the articles: setting (university versus community), study population (radiology series versus surgical series versus ED population), level of radiologist training and experience, inclusion criteria (all patients with suspected appendicitis versus those with equivocal presentations), CT slice type (helical versus conventional) and slice thickness (range 2.5 mm to 10 mm), enteric contrast protocol (type of oral contrast: barium, meglumine diatrizoate, diatrizoate sodium, or meglumine ioxitalamate), and contrast transit time (oral contrast transit times ranged from 40 minutes to longer than 2 hours).

To determine which CT technique is superior, CT techniques should be compared in a prospective, randomized trial. Only 3 studies have compared CT techniques head to head.²², ³², ⁵¹ Two of these 3 studies suggest that the addition of contrast does improve the diagnostic performance of CT.²², ³²

CT With Oral and IV Contrast Versus CT With Rectal Contrast Versus Noncontrast CT

Hershko et al³² published the only prospective randomized study comparing 3 different contrast protocols. CT with oral and IV contrast, and CT with rectal contrast were each more accurate than CT without contrast; CT with oral and IV contrast was more sensitive than CT with rectal contrast; CT with oral and IV contrast showed a trend toward increased sensitivity over CT without contrast. In this Class II study, Hershko et al³² randomized 232 consecutive patients with suspected appendicitis to one of 3 protocols: 70 patients had CT without contrast, 78 patients had CT with rectal contrast, and 84 patients had CT with oral and IV contrast. CT with rectal contrast and CT with oral and IV contrast were both more accurate than CT without contrast: 94%, 94%, and 70%, respectively (P<0.05). CT with oral and IV contrast was more sensitive than CT with rectal contrast, 100% (negative likelihood ratio 0) versus 93% (negative likelihood ratio 0.07) (P<0.05). CT with oral and IV contrast was observed to differ from CT without contrast with sensitivities of 100% (negative likelihood ratio 0) versus 90% (negative likelihood ratio 0.12), respectively; however, this difference did not achieve statistical significance.

CT With Oral Contrast Versus CT With Oral and IV Contrast

In a Class I study, Jacobs et al²² prospectively compared 2 different contrast protocols and concluded that IV contrast improved the sensitivity of CT. In a case-crossover-design trial that included 210 subjects, each patient had focused appendiceal CT with only oral contrast, followed by nonfocused abdomen and pelvis CT with oral and IV contrast. The sensitivity of the nonfocused abdomen and pelvis CT with oral and IV contrast was 91% (negative likelihood ratio 0.1), whereas the sensitivity of the focused appendiceal CT with oral contrast was 76% (negative likelihood ratio 0.26). The authors attributed the higher sensitivity of the nonfocused abdomen and pelvis CT to the use of IV contrast; they believed that IV contrast improved the ability of the radiologist to identify an inflamed appendix.

CT With Oral, Rectal, and IV Contrast Versus CT With Rectal Contrast

In a Class III study, Mittal et al⁵¹ compared the accuracy of 2 contrast protocols. The authors prospectively compared CT of the abdomen and pelvis with oral, rectal, and IV contrast to focused CT of the lower abdomen and pelvis with rectal contrast only. They found that CT with oral, rectal, and IV contrast had a sensitivity of 97% and specificity of 86% (negative likelihood ratio 0.04 and positive likelihood ratio 6.9), whereas CT with rectal contrast had a sensitivity of only 88% and a specificity of 100% (negative likelihood ratio 0.12 and an undefined positive likelihood ratio). The authors did not report whether these differences were statistically significant.

Inconclusive Results and Noncontrast CT

Noncontrast CT may produce inconclusive results. In the previously described study by Hershko et al,³² 14 (20%) of 70 patients in the CT without contrast group had inconclusive CT results. Nine (13%) patients had repeat CTs with oral and IV contrast. In a Class III study, Tamburrini et al²³ reported a CT protocol with selective use of contrast. Patients with suspected appendicitis were first evaluated with noncontrast CT of the abdomen and pelvis. Patients with inconclusive results were rescanned with contrast, the type of contrast determined on a case-by-case basis by the interpreting radiologist. The authors performed a retrospective review of 536 patients undergoing this protocol. Noncontrast CT was conclusive in 404 (75%) patients and inconclusive in 132 (25%). Repeat CT was performed with some type of contrast in 126 (24%) patients.

3. In children with suspected acute appendicitis who undergo diagnostic imaging, what are the roles of CT and ultrasound in diagnosing acute appendicitis?

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Patient Management Recommendations 

Level A recommendations 

None specified.

Level B recommendations 

Level C recommendations 

Given the concern over exposing children to ionizing radiation, consider using ultrasound as the initial imaging modality. In cases in which the diagnosis remains uncertain after ultrasound, CT may be performed.

Key words/phrases for literature searches: children, appendicitis, computed tomography, ultrasound, radiation, diagnosis, abdominal pain, sensitivity, specificity, and variations and combinations of the key words/phrases.

The diagnosis of acute appendicitis is challenging in the pediatric population, particularly among infants and toddlers. Missed or delayed diagnosis may result in perforation. Perforation rates for the pediatric population range from 17% to 57%,⁵² which may cause longer hospital stays, bowel obstruction, and sepsis.⁵³, ⁵⁴

CT has been advocated because it is an accurate diagnostic modality. However, CT is expensive and often requires contrast. CT also exposes the patient to ionizing radiation. Ultrasound has been advocated because it is fast, well tolerated, and safe.

Diagnostic Accuracy of Ultrasound

Ultrasound may be used to evaluate children for appendicitis and does not involve ionizing radiation exposure. Diagnostic criteria for appendicitis are an appendix greater than 6 mm in diameter, a noncompressible appendix, and appendiceal tenderness. However, the appendix may be obscured (by bowel gas) or difficult to find (eg, retrocecal position). The 7 studies that evaluate the diagnostic accuracy of ultrasound in pediatric appendicitis (Table 3) support the idea that ultrasound is better at positively identifying appendicitis than excluding it with a negative or equivocal result.⁵⁵, ⁵⁶, ⁵⁷, ⁵⁸, ⁵⁹, ⁶⁰, ⁶¹ For example, although 3 of the 7 studies listed in Table 3 report negative likelihood ratios for ultrasound less than 0.1,⁵⁵, ⁵⁹, ⁶¹ 5 of these 7 studies report positive likelihood ratios greater than 10.⁵⁵, ⁵⁶, ⁵⁸, ⁶⁰, ⁶¹

Table 3. Diagnostic accuracy of ultrasound in diagnosing acute appendicitis in children.

Reference	No. Subjects	Disease Prevalence, %	Positive LR	Negative LR	Sensitivity, %	Specificity, %	Class
Baldisserotto and Marchiori55	425	47	49.5	0.01	99(95% CI 97-100)	98(95% CI 97-99)	II
Kaiser et al56	283	41	17.2	0.14	86	95	II
Chang et al57	40	75	8.7	0.14	87	90	III
Dilley et al58	587	86	17.8	0.12	89	95	III
Lowe et al59	76	33	8.3	0	100	88	III
Sivit et al60	315	26	11.1	0.2	78	93	III
Teo et al61	129	22	31	0.07	93	97	III
Ranges	40-587 subjects	22-86	8.3-49.5	0-0.2	78-100	88-98	II-III

There are no Class I studies evaluating ultrasound for acute appendicitis in children. There are 2 Class II studies evaluating ultrasound in pediatric appendicitis.⁵⁵, ⁵⁶ Both studies are prospective evaluations that report positive likelihood ratios from 17.2 to 49.5 and negative likelihood ratios from 0.01 to 0.14. Baldisserotto and Marchiori⁵⁵ was limited by lack of operator (ie, radiologist) blinding. Also, the ultrasound technique used by Baldisserotto and Marchiori⁵⁵ did not assess compressibility of the appendix (a diagnostic criterion in most studies). In the study by Kaiser et al,⁵⁶ ultrasound results were interpreted by pediatric surgeons and surgical residents, not radiologists. This limited the study's generalizability.

Of the 5 Class III ultrasound studies, 3 are prospective⁵⁷, ⁶⁰, ⁶¹ and 2 are retrospective.⁵⁸, ⁵⁹ These Class III studies report positive likelihood ratios from 8.3 to 31 and negative likelihood ratios from 0 to 0.2. Of these prospective Class III studies, the study by Chang et al⁵⁷ had a small sample size (40 subjects). Two of the studies did not adequately identify or describe the outpatient follow-up of subjects with negative study results.⁶⁰, ⁶¹ The ultrasound outcomes from the study by Lowe et al⁵⁹ were taken from the retrospective control arm of a prospective study. Lowe et al⁵⁹ also did not describe the duration of outpatient follow-up of subjects with negative study results, and their study had a relatively small sample size (76 subjects). Dilley et al⁵⁸ did not describe a criterion standard for outpatient follow-up of negative ultrasound results.

Diagnostic Accuracy of Abdominal and Pelvic CT

According to Class II and III evidence, CT is better than ultrasound at confirming and excluding appendicitis. Seven studies evaluated abdominal CT in diagnosing pediatric appendicitis⁵⁹, ⁶⁰, ⁶², ⁶³, ⁶⁴, ⁶⁵, ⁶⁶ (Table 4). Of the 7 studies that evaluated CT for pediatric appendicitis, all study arms that involved the use of some type of contrast reported negative likelihood ratios less than 0.1, and all but one study⁶⁶ involving some type of contrast reported positive likelihood ratios greater than 10. All studies except one⁶⁶ reported specificities of 90% or greater. Specifically, 2 Class III studies of rectal contrast only reported positive likelihood ratios from 50 to 97 and negative likelihood ratios from 0 to 0.03 for acute appendicitis.⁶³, ⁶⁵

Table 4. Diagnostic accuracy of CT in diagnosing acute appendicitis in children.

Reference	No. Subjects	Disease Prevalence, %	Contrast Type	Positive LR	Negative LR	Sensitivity, %	Specificity, %	Class
Lowe et al59	72	33	None	Undefined	0.03	97	100	II
Kaiser et al62	306	42	Either no contrast or just IV contrast	No contrast: 6.6; IV contrast: 16	No contrast: 0.38; IV contrast: 0.04	No contrast: 66; IV contrast: 96	No contrast: 90; IV contrast: 94	II
Sivit et al60	153	26	IV in 145/153(95%), and oral or rectal in 151/153(99%)	13.6	0.05	95	93	III
Acosta et al63	94	16	Rectal (alone)	50	0	100(95% CI 66-100)	98(95% CI 88-100)	III
Hoecker and Billman64	112	38	None	14.7	0.13	88(95% CI 76-95)	94(95% CI 95-98)	III
Mullins et al65	199	33	Rectal (alone)	97	0.03	97	99	III
Kharbanda et al66	416	40	Either IV alone or IV and rectal	IV alone: 11.6; IV and rectal: 7.1	IV alone: 0.08; IV and rectal: 0.09	IV alone: 93(95% CI 84-97); IV and rectal: 92(95% CI 85-97)	IV alone: 92(95% CI 85-96); IV and rectal: 87(95% CI 79-92)	III
Ranges	72-416	16-42		No contrast: 6.6-undefined; rectal contrast: 50-97; IV contrast: 11.6-16; IV and rectal contrast: 7.1; all results: 6.6-undefined	No contrast: 0.03-0.38; rectal contrast: 0-0.03; IV contrast: 0.04-0.08; IV and rectal contrast: 0.09; all results: 0-0.38	No contrast: 66-97; rectal contrast: 97-100; IV contrast: 93-96; IV and rectal contrast: 92; all results: 66-100	No contrast: 90-100; rectal contrast: 98-99; IV contrast: 92-94; IV and rectal contrast: 87; all results: 87-100	II-III

Four of these studies were prospective⁵⁹, ⁶⁰, ⁶², ⁶³ and 3 were retrospective.⁶⁴, ⁶⁵, ⁶⁶ Limitations of the articles by Lowe et al⁵⁹ and Sivit et al⁶⁰ are discussed under the ultrasound section. CT outcomes from the study by Lowe et al⁵⁹ were graded as Class II because the data were collected prospectively.

The Class II 2004 study by Kaiser et al⁶² was based on CT scans from their 2002 study. These scans were reread by 3 radiologists who were blinded to patient outcomes and compared with outcomes from the 2002 study. The prospective study by Acosta et al⁶³ was limited by sample size (43 children included in outcomes calculations), generalizability (excluded children younger than 6 years), and potential bias (CT scans read by 1 radiologist). In 2007, Kharbanda et al⁶⁶ retrospectively studied 416 children who received a CT with either IV or IV and rectal contrast. Although Kharbanda et al⁶⁶ collected data retrospectively, the study was designed to occur throughout 2 consecutive study periods, during which children received one of the 2 CT techniques. In the study by Hoecker and Billman,⁶⁴ which was retrospective, 15 of 112 children were lost to follow-up. Mullins et al⁶⁵ conducted a retrospective study that had possible selection bias; children chosen for study may have been more clinically straightforward.

We found no prospective, randomized comparisons of ultrasound and CT for pediatric appendicitis. Three studies attempted to compare CT and ultrasound.⁵⁶, ⁵⁹, ⁶⁰ The Sivit et al⁶⁰ study was not randomized, Lowe et al⁵⁹ used a historical control group, and Kaiser et al⁵⁶ compared CT with ultrasound followed by CT.

The value of using CT with oral and IV contrast to diagnose appendicitis in children remains unclear. We found no direct evaluation of the diagnostic performance of oral and IV contrast alone for appendicitis in children. Nevertheless, some clinicians use oral and IV contrast to diagnose pediatric appendicitis according to the adult literature (discussed under critical question 2 about the role of contrast in CT for acute appendicitis in adults). Most children are smaller than adults and may have different peritoneal fat distributions. The question of whether or not adult outcomes (for CT in appendicitis) can be applied to children of all ages and sizes remains unanswered.

Ionizing Radiation and CT

There are no prospective studies that prove a link between CT and cancer in children. However, 2 Class III unstructured reviews argue that, because ionizing radiation at high doses (eg, atomic bomb) is associated with cancer, and this high-dose risk may proceed in a predictable fashion with dose, there may be a similar but small risk to children receiving diagnostic radiologic procedures (eg, CT).⁶⁷, ⁶⁸

Another Class III article develops the argument supporting the risk of ionizing radiation from CT in a slightly different way.⁶⁹ Brenner and Hall⁶⁹ first present data that about 30% of patients who receive an abdominal and pelvic CT also receive at least 3 such CT scans in the course of their care. The authors then present data that atomic bomb survivors who received 50 to 150 mSv^⁎ of radiation had a small increase in cancer risk. Two to 3 abdominal/pelvic CT scans expose patients to a level of millisieverts similar to that of some atomic bomb survivors who developed cancer. Extrapolating backwards, the authors estimate the lifetime attributable risk of all cancers from 1 abdominal and pelvic CT to be 0.14% in neonates and approximately 0.06% in adults. Children have a higher risk of developing cancer after radiation exposure because they have more years to develop those cancers and are more radiosensitive (children have more actively dividing cells than adults).

In an effort to limit ionizing radiation exposure, some centers are using a staged approach by initially using ultrasound, and then using CT either to confirm or exclude the diagnosis in selected cases.⁷⁰, ⁷¹ At this writing, this strategy has not been definitively validated in prospective studies.

Future Areas of Research 

The following are suggestions for future research:

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Relevant industry relationships of subcommittee members: There were no relevant industry relationships disclosed by the subcommittee members.

Relevant industry relationships are those relationships with companies associated with products or services that significantly impact the specific aspect of disease addressed in the critical question.

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Appendix 

Appendix A. Literature classification schema.^⁎

Appendix B. Approach to downgrading strength of evidence

Appendix C. Likelihood ratios.

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• ⁎ Millisieverts are the measure of radiation dose to organs, and this measurement is generally used in risk assessments of radiation.