Table of Contents

 

The dangers associated with misdiagnosis, delay, and perforation make quick and accurate diagnosis of appendicitis essential. This issue provides guidance for the management of children with appendicitis, including recommendations for diagnostic studies, pain management, prophylactic antibiotics, and surgical consultation. You will learn:

Age-based historical and physical examination findings that can narrow the differential diagnosis, including common signs of appendicitis (eg, Rovsing sign, pain upon coughing or hopping, and right iliac fossa tenderness)

Clinical scoring systems that can help guide the workup of appendicitis in children, including the pediatric appendicitis risk calculator (pARC), the pediatric appendicitis score (PAS), and the Alvarado score

Why ultrasound is recommended as the initial imaging study for patients with suspected appendicitis, and which imaging studies can be used when the ultrasound is equivocal

Appropriate initial stabilization strategies for patients with acute appendicitis

Recommendations for pain management and prophylactic antibiotics

Which patients may be candidates for nonoperative management

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Epidemiology and Pathophysiology
   1. Epidemiology
   2. Pathophysiology
6. Differential Diagnosis
7. Prehospital Care
8. Emergency Department Evaluation
   1. Age-Specific Considerations
      1. Infants
      2. Prepubertal Children
      3. Postpubertal Children
   2. General Considerations
   3. Physical Examination
9. Diagnostic Studies
   1. Scoring Systems
   2. Laboratory Studies
      1. White Blood Cell Count
      2. C-Reactive Protein
      3. Urinalysis
   3. Imaging Studies
      1. Ultrasound
      2. Computed Tomography
      3. Magnetic Resonance Imaging
      4. Selection of Imaging Study
10. Treatment
11. Special Populations
    1. Appendicitis in Children Aged < 5 Years
    2. Appendicitis in Pregnant Patients
12. Controversies and Cutting Edge
    1. New Scoring Systems
    2. Nonoperative Management
13. Disposition
14. Summary
15. Time- and Cost-Effective Strategies
16. Risk Management Pitfalls in the Management of Appendicitis in Pediatric Patients
17. Case Conclusions
18. Clinical Pathway for the Diagnosis of Appendicitis in Pediatric Patients
19. Tables and Figures
    1. Table 1. Differential Diagnosis of Right Lower Quadrant Abdominal Pain
    2. Table 2. Pediatric Appendicitis Score (PAS)
    3. Table 3. Alvarado Scoring System
    4. Figure 1. Ultrasound Images of Acute Appendicitis in a Child
20. References

Abstract

Appendicitis is the most common condition in children requiring emergency abdominal surgery. Delayed or missed diagnosis in young children is common and is associated with increased rates of perforation. Although several scoring systems have been developed, there is still no consensus on clinical, laboratory, and imaging criteria for diagnosing appendicitis. This issue reviews key age-based historical and physical examination findings, as well as clinical scoring systems, that can help guide the workup of appendicitis in children. The existing literature is reviewed to provide guidance for the management of children with appendicitis, including recommendations for diagnostic studies, prophylactic antibiotics, pain medication, and surgical consultation.

Case Presentations

An 11-year-old previously healthy boy presents to the ED on a busy Saturday evening. He has acute abdominal pain that started 18 hours ago as diffuse periumbilical abdominal pain. Within the last 3 hours or so, the pain migrated to the right lower quadrant and worsened in severity. The child says the bumps on the car ride to the hospital were painful, and hopping up and down makes the pain worse. He says it seems to be a bit better when he lies still and does not move. Oral ibuprofen has not really helped the pain. The patient has not eaten a meal all day and has vomited 3 times today. On presentation, he has a temperature of 38.3°C (101°F). He is fully immunized and does not have any upper respiratory symptoms. He has never had similar pain in the past and has no history of previous abdominal surgeries. He has a normal genitourinary examination. He has obvious discomfort with palpation of his abdomen with maximum tenderness in the right lower quadrant. He exhibits guarding and rebound tenderness. His mother asks you whether this could be appendicitis, and whether he will need surgery. You begin to think… Is this appendicitis? What else could it be? How will you definitively determine the diagnosis? What laboratory evaluation and imaging tests should you order? It is now 2:00 AM. If the patient definitely has appendicitis, does he need an emergent appendectomy or can it wait?

Your next patient is a 16-year-old girl with abdominal pain who is brought into the ED by her mother. When the girl arrived to the ED, her vital signs were age-appropriate except for tachycardia, with a heart rate of 115 beats/min. Initially, she had some mild pain in her lower abdomen that gradually got worse. What is your differential diagnosis? What history, physical examination findings, or diagnostic evaluations should you obtain?

Your last patient of the evening is a 4-year-old boy with abdominal pain who is brought into the ED by his parents. The parents report that the boy was at his baseline state of health until 2 days ago when he became more fatigued and did not want to play as much. Today, he has had poor oral intake and spiked a fever to 38.6°C (101.5°F). The patient has been moaning and seems to grab at his abdomen in pain. Again, the diagnosis of appendicitis comes to mind. Is the rate of perforated appendicitis higher in this age group? How do you get an accurate history and perform a physical examination if the child will not talk to you and cowers behind his father when you approach him?

Introduction

Abdominal pain is a common chief complaint for pediatric patients presenting to an emergency department (ED) and, most of the time, the etiology is self-limited and nonemergent. Nonetheless, acute appendicitis must be considered in the differential diagnosis of abdominal pain in the pediatric population because missed acute appendicitis can lead to morbidity and mortality as well as medicolegal consequences.

In children, acute appendicitis is the most common condition requiring emergency surgery, with > 75,000 children diagnosed annually in the United States.¹ The potential for morbidity and mortality from perforation of the appendix necessitates prompt diagnosis.² Although a variety of clinical scoring systems have been developed, there is still no consensus on clinical, laboratory, and imaging criteria for diagnosing appendicitis, which poses a dilemma for the emergency clinician.^3-5

This issue of Pediatric Emergency Medicine Practice reviews the existing literature to help develop strategies for the diagnosis and management of appendicitis in the pediatric population.

Critical Appraisal of the Literature

A literature search was performed in PubMed using the search terms appendicitis, abdominal pain, pediatrics, clinical scoring systems, ultrasound, diagnostic tests, radiation risk, and non-operative management. An English language filter was applied, and articles were sorted by relevance. Several thousand articles were found, with over 1000 screened by title, then abstract. A total of 101 articles were chosen for inclusion.

There are many deficiencies inherent to the quality of the literature, including the lack of pediatric studies and more retrospective studies. According to standard evidence-level scales, the majority of evidence for pediatric appendicitis falls into the “weak” or “moderately strong” categories, and there are many single-center studies with limited enrollment. There is an article from the Effective Health Care Program on the “Diagnosis of Right Lower Quadrant Pain and Suspected Appendicitis” in the National Guidelines Clearinghouse.⁶ Despite these studies, there is no clear consensus on the approach to the pediatric patient with abdominal pain.

Risk Management Pitfalls in the Management of Appendicitis in Pediatric Patients

1. “I saw this patient in the ED 2 days ago. He presented with 2 hours of vague abdominal pain, and his exam was not consistent with acute appendicitis. I can't believe he is back today with a perforated appendix.”

Early appendicitis can present with vague abdominal pain with a broad differential diagnosis. Therefore, it can be easy to miss early appendicitis. If a patient presents to the ED with < 24 hours of abdominal pain or the diagnosis is equivocal, close follow-up with a primary care provider or ED follow-up should be ensured if the patient’s symptoms persist.

8. “This 3-year-old boy seemed to have abdominal pain on exam, but he had a normal appendix ultrasound. He re-presented to the ED 2 days later with a large right-sided basilar pneumonia.”

The preverbal child can be difficult to examine in the ED. Even though it is true that children aged < 5 years with appendicitis often present with a perforated appendix, other diagnoses are much more common in this age group and should be considered. Failing to consider a broad differential may result in missed pathology.

9. “I decided to withhold morphine from my 8-year-old patient with suspected appendicitis. I didn’t want to miss a diagnosis because I administered an analgesic.”

Early analgesia is recommended. There is no increase in missed appendicitis or in negative appendectomies after analgesia. Adequate pain control for patients with suspected appendicitis in the ED is imperative.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

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2. Pena BM, Taylor GA, Fishman SJ, et al. Costs and effectiveness of ultrasonography and limited computed tomography for diagnosing appendicitis in children. Pediatrics. 2000;106(4):672-676. (Prospective; 139 patients)
3. Samuel M. Pediatric appendicitis score. J Pediatr Surg. 2002;37(6):877-881. (Prospective; 1170 patients)
4. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med. 1986;15(5):557-564. (Retrospective; 305 patients)
5. Kharbanda AB, Vazquez-Benitez G, Ballard DW, et al. Development and validation of a novel pediatric appendicitis risk calculator (pARC). Pediatrics. 2018;141(4). (Prospective; 3849 patients)
6. Dahabreh IJ, Adam GP, Halladay CW, et al. AHRQ comparative effectiveness reviews. Diagnosis of Right Lower Quadrant Pain and Suspected Acute Appendicitis. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015. (Meta-analysis; 903 studies)
7. Reynolds SL, Jaffe DM. Diagnosing abdominal pain in a pediatric emergency department. Pediatr Emerg Care. 1992;8(3):126-128. (Prospective; 377 patients)
8. Scholer SJ, Pituch K, Orr DP, et al. Clinical outcomes of children with acute abdominal pain. Pediatrics. 1996;98(4 Pt 1):680-685. (Retrospective; 1141 patients)
9. Rothrock SG, Pagane J. Acute appendicitis in children: emergency department diagnosis and management. Ann Emerg Med. 2000;36(1):39-51. (Review)
10. Almaramhy HH. Acute appendicitis in young children less than 5 years: review article. Ital J Pediatr. 2017;43(1):15. (Review)
11. Rothrock SG, Skeoch G, Rush JJ, et al. Clinical features of misdiagnosed appendicitis in children. Ann Emerg Med. 1991;20(1):45-50. (Retrospective; 181 patients)
12. Nance ML, Adamson WT, Hedrick HL. Appendicitis in the young child: a continuing diagnostic challenge. Pediatr Emerg Care. 2000;16(3):160-162. (Retrospective; 132 patients)
13. Addiss DG, Shaffer N, Fowler BS, et al. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990;132(5):910-925. (Retrospective; 3.4 million appendectomies)
14. Caperell K, Pitetti R, Cross KP. Race and acute abdominal pain in a pediatric emergency department. Pediatrics. 2013;131(6):1098-1106. (Retrospective; 9424 patients)
15. Wang L, Haberland C, Thurm C, et al. Health outcomes in US children with abdominal pain at major emergency departments associated with race and socioeconomic status. PLoS One. 2015;10(8):e0132758. (Retrospective; 4.2 million patient encounters)
16. Smink DS, Fishman SJ, Kleinman K, et al. Effects of race, insurance status, and hospital volume on perforated appendicitis in children. Pediatrics. 2005;115(4):920-925. (Retrospective; 33,184 patients)
17. Buschard K, Kjaeldgaard A. Investigation and analysis of the position, fixation, length and embryology of the vermiform appendix. Acta Chir Scand. 1973;139(3):293-298. (Prospective; 292 patients)
18. Guidry SP, Poole GV. The anatomy of appendicitis. Am Surg. 1994;60(1):68-71. (Prospective; 100 patients)
19. Bundy DG, Byerley JS, Liles EA, et al. Does this child have appendicitis? JAMA. 2007;298(4):438-451. (Review)
20. Guillet-Caruba C, Cheikhelard A, Guillet M, et al. Bacteriologic epidemiology and empirical treatment of pediatric complicated appendicitis. Diagn Microbiol Infect Dis. 2011;69(4):376-381. (Prospective; 93 patients)
21. Rabah R. Pathology of the appendix in children: an institutional experience and review of the literature. Pediatr Radiol. 2007;37(1):15-20. (Review)
22. Jeon HG, Ju HU, Kim GY, et al. Bacteriology and changes in antibiotic susceptibility in adults with community-acquired perforated appendicitis. PLoS One. 2014;9(10):e111144. (Retrospective; 415 patients)
23. Lamps LW. Infectious causes of appendicitis. Infect Dis Clin North Am. 2010;24(4):995-1018. (Review)
24. Connor SJ, Hanna GB, Frizelle FA. Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7,970 appendectomies. Dis Colon Rectum. 1998;41(1):75-80. (Retrospective; 7970 appendectomies)
25. Doede T, Foss HD, Waldschmidt J. Carcinoid tumors of the appendix in children--epidemiology, clinical aspects and procedure. Eur J Pediatr Surg. 2000;10(6):372-377. (Retrospective; 4747 appendectomies)
26. Goede AC, Caplin ME, Winslet MC. Carcinoid tumour of the appendix. Br J Surg. 2003;90(11):1317-1322. (Review)
27. Kanthan R, Saxena A, Kanthan SC. Goblet cell carcinoids of the appendix: immunophenotype and ultrastructural study. Arch Pathol Lab Med. 2001;125(3):386-390. (Case series; 7 cases)
28. Galai T, Beloosesky OZ, Scolnik D, et al. Misdiagnosis of acute appendicitis in children attending the emergency department: the experience of a large, tertiary care pediatric hospital. Eur J Pediatr Surg. 2017;27(2):138-141. (Retrospective; 400 patients)
29. Alloo J, Gerstle T, Shilyansky J, et al. Appendicitis in children less than 3 years of age: a 28-year review. Pediatr Surg Int. 2004;19(12):777-779. (Retrospective; 27 patients)
30. Graham JM, Pokorny WJ, Harberg FJ. Acute appendicitis in preschool age children. Am J Surg. 1980;139(2):247-250. (Retrospective; 183 patients)
31. O’Shea JS, Bishop ME, Alario AJ, et al. Diagnosing appendicitis in children with acute abdominal pain. Pediatr Emerg Care. 1988;4(3):172-176. (Prospective; 246 patients)
32. Benabbas R, Hanna M, Shah J, et al. 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. Acad Emerg Med. 2017;24(5):523-551. (Systematic review and meta-analysis; 21 studies, 8605 patients)
33. Goldman RD, Carter S, Stephens D, et al. Prospective validation of the pediatric appendicitis score. J Pediatr. 2008;153(2):278-282. (Prospective; 849 patients)
34. Schneider C, Kharbanda A, Bachur R. Evaluating appendicitis scoring systems using a prospective pediatric cohort. Ann Emerg Med. 2007;49(6):778-784. (Prospective; 588 patients)
35. Ebell MH, Shinholser J. What are the most clinically useful cutoffs for the Alvarado and pediatric appendicitis scores? A systematic review. Ann Emerg Med. 2014;64(4):365-372.e362. (Review article)
36. Cotton DM, Vinson DR, Vazquez-Benitez G, et al. Validation of the pediatric appendicitis risk calculator (pARC) in a community emergency department setting. Ann Emerg Med. 2019. (Prospective; 2089 patients)
37. Bachur RG, Dayan PS, Dudley NC, et al. The influence of age on the diagnostic performance of white blood cell count and absolute neutrophil count in suspected pediatric appendicitis. Acad Emerg Med. 2016;23(11):1235-1242. (Prospective; 2133 patients)
38. Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg. 2004;91(1):28-37. (Meta-analysis; 24 studies)
39. Kharbanda AB, Taylor GA, Fishman SJ, et al. A clinical decision rule to identify children at low risk for appendicitis. Pediatrics. 2005;116(3):709-716. (Prospective; 601 patients)
40. Gronroos JM, Gronroos P. Leucocyte count and C-reactive protein in the diagnosis of acute appendicitis. Br J Surg. 1999;86(4):501-504. (Retrospective; 300 patients)
41. Yang HR, Wang YC, Chung PK, et al. Laboratory tests in patients with acute appendicitis. ANZ J Surg. 2006;76(1-2):71-74. (Retrospective; 897 patients)
42. Beltran MA, Almonacid J, Vicencio A, et al. Predictive value of white blood cell count and C-reactive protein in children with appendicitis. J Pediatr Surg. 2007;42(7):1208-1214. (Retrospective; 198 patients)
43. Anandalwar SP, Callahan MJ, Bachur RG, et al. Use of white blood cell count and polymorphonuclear leukocyte differential to improve the predictive value of ultrasound for suspected appendicitis in children. J Am Coll Surg. 2015;220(6):1010-1017. (Retrospective; 845 patients)
44. Kim HC, Yang DM, Lee CM, et al. Acute appendicitis: relationships between CT-determined severities and serum white blood cell counts and C-reactive protein levels. Br J Radiol. 2011;84(1008):1115-1120. (Retrospective; 128 patients)
45. Yu CW, Juan LI, Wu MH, et al. Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis. Br J Surg. 2013;100(3):322-329. (Review)
46. Campbell JP, Gunn AA. Plain abdominal radiographs and acute abdominal pain. Br J Surg. 1988;75(6):554-556. (Retrospective; 5080 patients)
47. Pezone I, Iezzi ML, Leone S. Retrocardiac pneumonia mimicking acute abdomen: a diagnostic challenge. Pediatr Emerg Care. 2012;28(11):1230-1231. (Case report)
48. Knight PJ, Vassy LE. Specific diseases mimicking appendicitis in childhood. Arch Surg. 1981;116(6):744-746. (Retrospective; 1039 patients)
49. Kosloske AM, Love CL, Rohrer JE, et al. The diagnosis of appendicitis in children: outcomes of a strategy based on pediatric surgical evaluation. Pediatrics. 2004;113(1 Pt 1):29-34. (Retrospective; 356 patients)
50. Partrick DA, Janik JE, Janik JS, et al. Increased CT scan utilization does not improve the diagnostic accuracy of appendicitis in children. J Pediatr Surg. 2003;38(5):659-662. (Retrospective; 616 patients)
51. Puylaert JB. Acute appendicitis: US evaluation using graded compression. Radiology. 1986;158(2):355-360. (Prospective; 60 patients)
52. Baldisserotto M, Marchiori E. Accuracy of noncompressive sonography of children with appendicitis according to the potential positions of the appendix. AJR Am J Roentgenol. 2000;175(5):1387-1392. (Prospective; 425 patients)
53. Lee JH, Jeong YK, Hwang JC, et al. Graded compression sonography with adjuvant use of a posterior manual compression technique in the sonographic diagnosis of acute appendicitis. AJR Am J Roentgenol. 2002;178(4):863-868. (Prospective; 570 patients)
54. Doria AS, Moineddin R, Kellenberger CJ, et al. US or CT for diagnosis of appendicitis in children and adults? A meta-analysis. Radiology. 2006;241(1):83-94. (Meta-analysis; 26 studies, 9356 children and 31 studies, 4341 adults)
55. Schuh S, Man C, Cheng A, et al. Predictors of non-diagnostic ultrasound scanning in children with suspected appendicitis. J Pediatr. 2011;158(1):112-118. (Prospective; 263 patients)
56. Goldin AB, Khanna P, Thapa M, et al. Revised ultrasound criteria for appendicitis in children improve diagnostic accuracy. Pediatr Radiol. 2011;41(8):993-999. (Retrospecitve; 304 patients)
57. Worrell JA, Drolshagen LF, Kelly TC, et al. Graded compression ultrasound in the diagnosis of appendicitis. A comparison of diagnostic criteria. J Ultrasound Med. 1990;9(3):145-150. (Retrospective; 200 patients)
58. Vignault F, Filiatrault D, Brandt ML, et al. Acute appendicitis in children: evaluation with US. Radiology. 1990;176(2):501-504. (Prospective; 70 patients)
59. Partain KN, Patel A, Travers C, et al. Secondary signs may improve the diagnostic accuracy of equivocal ultrasounds for suspected appendicitis in children. J Pediatr Surg. 2016;51(10):1655-1660. (Retrospecitve; 825 patients)
60. Hahn HB, Hoepner FU, Kalle T, et al. Sonography of acute appendicitis in children: 7 years experience. Pediatr Radiol. 1998;28(3):147-151. (Retrospective; 3859)
61. Wiersma F, Toorenvliet BR, Bloem JL, et al. US examination of the appendix in children with suspected appendicitis: the additional value of secondary signs. Eur Radiol. 2009;19(2):455-461. (Retrospective; 212 patients)
62. Nordin AB, Sales S, Nielsen JW, et al. Standardized ultrasound templates for diagnosing appendicitis reduce annual imaging costs. J Surg Res. 2018;221:77-83. (Quality improvement)
63. Partain KN, Patel AU, Travers C, et al. Improving ultrasound for appendicitis through standardized reporting of secondary signs. J Pediatr Surg. 2016. (Quality improvement; 870 patients)
64. Nielsen JW, Boomer L, Kurtovic K, et al. Reducing computed tomography scans for appendicitis by introduction of a standardized and validated ultrasonography report template. J Pediatr Surg. 2015;50(1):144-148. (Quality improvement)
65. Williamson K, Sherman JM, Fishbein JS, et al. Outcomes for children with a nonvisualized appendix on ultrasound. Pediatr Emerg Care. 2018. (Retrospective; 3245 ultrasounds)
66. Lowe LH, Perez R Jr, Scheker LE, et al. Appendicitis and alternate diagnoses in children: findings on unenhanced limited helical CT. Pediatr Radiol. 2001;31(8):569-577. (Review)
67. Sivit CJ, Applegate KE, Stallion A, et al. Imaging evaluation of suspected appendicitis in a pediatric population: effectiveness of sonography versus CT. AJR Am J Roentgenol. 2000;175(4):977-980. (Prospective; 386 patients)
68. Kharbanda AB, Taylor GA, Bachur RG. Suspected appendicitis in children: rectal and intravenous contrast-enhanced versus intravenous contrast-enhanced CT. Radiology. 2007;243(2):520-526. (Retrospective; 416 patients)
69. Laituri CA, Fraser JD, Aguayo P, et al. The lack of efficacy for oral contrast in the diagnosis of appendicitis by computed tomography. J Surg Res. 2011;170(1):100-103. (Retrospective; 1561 patients)
70. Bachur RG, Dayan PS, Bajaj L, et al. The effect of abdominal pain duration on the accuracy of diagnostic imaging for pediatric appendicitis. Ann Emerg Med. 2012;60(5):582-590. (Prospective; 1810 patients)
71. Miglioretti DL, Johnson E, Williams A, et al. The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr. 2013;167(8):700-707. (Retrospective observational; 5,857,736 child years)
72. Yu YR, Shah SR. Can the diagnosis of appendicitis be made without a computed tomography scan? Adv Surg. 2017;51(1):11-28. (Review)
73. Kim JR, Suh CH, Yoon HM, et al. Performance of MRI for suspected appendicitis in pediatric patients and negative appendectomy rate: a systematic review and meta-analysis. J Magn Reson Imaging. 2018;47(3):767-778. (Systematic review and meta-analysis; 13 studies, 1946 patients)
74. Moore MM, Kulaylat AN, Hollenbeak CS, et al. Magnetic resonance imaging in pediatric appendicitis: a systematic review. Pediatr Radiol. 2016;46(6):928-939. (Systematic review)
75. Duke E, Kalb B, Arif-Tiwari H, et al. A systematic review and meta-analysis of diagnostic performance of MRI for evaluation of acute appendicitis. AJR Am J Roentgenol. 2016;206(3):508-517. (Systematic review and meta-analysis; 30 studies, 2665 patients)
76. Aspelund G, Fingeret A, Gross E, et al. Ultrasonography/MRI versus CT for diagnosing appendicitis. Pediatrics. 2014;133(4):586-593. (Retrospective; 662 patients)
77. Dibble EH, Swenson DW, Cartagena C, et al. Effectiveness of a staged US and unenhanced MR imaging algorithm in the diagnosis of pediatric appendicitis. Radiology. 2018;286(3):1022-1029. (Retrospective; 1982 patients)
78. Flood TF, Stence NV, Maloney JA, et al. Pediatric brain: repeated exposure to linear gadolinium-based contrast material is associated with increased signal intensity at unenhanced T1-weighted MR imaging. Radiology. 2017;282(1):222-228. (Retrospective; 46 patients)
79. Kharbanda AB, Christensen EW, Dudley NC, et al. Economic analysis of diagnostic imaging in pediatric patients with suspected appendicitis. Acad Emerg Med. 2018;25(7):785-794. (Prospective; 2300 patients)
80. Fullerton K, Depinet H, Iyer S, et al. Association of hospital resources and imaging choice for appendicitis in pediatric emergency departments. Acad Emerg Med. 2017;24(4):400-409. (Retrospective; 1090 patients)
81. Gregory S, Kuntz K, Sainfort F, et al. Cost-effectiveness of integrating a clinical decision rule and staged imaging protocol for diagnosis of appendicitis. Value Health. 2016;19(1):28-35. (Conceptual model)
82. Green R, Bulloch B, Kabani A, et al. Early analgesia for children with acute abdominal pain. Pediatrics. 2005;116(4):978-983. (Prospective randomized controlled; 108 patients)
83. Poonai N, Paskar D, Konrad SL, et al. Opioid analgesia for acute abdominal pain in children: a systematic review and meta-analysis. Acad Emerg Med. 2014;21(11):1183-1192. (Systematic review and meta-analysis; 342 patients)
84. Robb AL, Ali S, Poonai N, et al. Pain management of acute appendicitis in Canadian pediatric emergency departments. Cjem. 2017;19(6):417-423. (Retrospective; 619 patients)
85. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11(1):79-109. (Executive summary of guidelines)
86. Bhangu A. Safety of short, in-hospital delays before surgery for acute appendicitis: multicentre cohort study, systematic review, and meta-analysis. Ann Surg. 2014;259(5):894-903. (Review)
87. Cameron DB, Williams R, Geng Y, et al. Time to appendectomy for acute appendicitis: a systematic review. J Pediatr Surg. 2018;53(3):396-405. (Review)
88. Stevenson MD, Dayan PS, Dudley NC, et al. Time from emergency department evaluation to operation and appendiceal perforation. Pediatrics. 2017;139(6). (Prospective; 955 patients)
89. Bachur RG, Lipsett SC, Monuteaux MC. Outcomes of nonoperative management of uncomplicated appendicitis. Pediatrics. 2017;140(1):e20170048. (Retrospective; 99,001 patients)
90. Mourad J, Elliott JP, Erickson L, et al. Appendicitis in pregnancy: new information that contradicts long-held clinical beliefs. Am J Obstet Gynecol. 2000;182(5):1027-1029. (Retrospective; 66,993 deliveries)
91. Richards C, Daya S. Diagnosis of acute appendicitis in pregnancy. Can J Surg. 1989;32(5):358-360. (Case control; 28 patients)
92. Barloon TJ, Brown BP, Abu-Yousef MM, et al. Sonography of acute appendicitis in pregnancy. Abdom Imaging. 1995;20(2):149-151. (Case series; 22 sonograms)
93. Kanal E, Barkovich AJ, Bell C, et al. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol. 2007;188(6):1447-1474. (Clinical guidelines)
94. Theilen LH, Mellnick VM, Longman RE, et al. Utility of magnetic resonance imaging for suspected appendicitis in pregnant women. Am J Obstet Gynecol. 2015;212(3):345.e341-346. (Retrospective; 171 patients)
95. Bickell NA, Aufses AH Jr, Rojas M, et al. How time affects the risk of rupture in appendicitis. J Am Coll Surg. 2006;202(3):401-406. (Retrospective; 219 patients)
96. Yilmaz HG, Akgun Y, Bac B, et al. Acute appendicitis in pregnancy--risk factors associated with principal outcomes: a case control study. Int J Surg. 2007;5(3):192-197. (Case control; 52 patients)
97. McGory ML, Zingmond DS, Tillou A, et al. Negative appendectomy in pregnant women is associated with a substantial risk of fetal loss. J Am Coll Surg. 2007;205(4):534-540. (Retrospective; 94,789 patients)
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