The Implications of Missed Opportunities to Diagnose Appendicitis in Children

ORIGINAL RESEARCH CONTRIBUTION The Implications of Missed Opportunities to Diagnose Appendicitis in Children Jessica A. Naiditch, MD, Timothy B. Lautz, MD, Susan Daley, MD, Mary Clyde Pierce, MD, and Marleta Reynolds, MD Abstract Objectives: The purpose of this study was to determine the fraction of children with acute appendicitis who had recent false-negative diagnoses and to analyze the association of a missed diagnosis of appendicitis with patient outcome. Methods: The records of all 816 patients who underwent appendectomy for suspected appendicitis at a free-standing children s hospital between 2007 and 2010 were reviewed. A patient admitted or evaluated in the emergency department (ED), discharged without a diagnosis of appendicitis, and then readmitted with histopathologically confirmed appendicitis within 3 days was considered to have a missed diagnosis. Outcomes for this missed group were compared to those of the remainder of the appendectomy cohort. Results: Thirty-nine patients with appendicitis (4.8%) were missed at initial presentation. The most common initial discharge diagnoses were acute gastroenteritis (43.6%), constipation (10.3%), and emesis (10.3%). The median duration from the initial evaluation to the appendicitis admission was 28.3 hours (interquartile range [IQR] = 17.0 to 39.6 hours). A missed diagnosis was associated with a longer median hospitalization (5.8 days [IQR = 4.0 to 8.1 days] vs. 2.5 days [IQR = 1.8 to 4.6 days]; p < 0.001), higher rate of perforation (74.4% vs. 29.0%; p < 0.001), higher complication rate (28.2% vs. 10.4%; p = 0.002), and higher rate of reintervention (20.5% vs. 6.2%; p = 0.003). Conclusions: Of children diagnosed with appendicitis, 4.8% may have had a missed opportunity for earlier diagnosis. These false-negative diagnoses are associated with higher rates of perforation, postoperative complications, and need for postoperative interventions, as well as longer hospitalizations. ACADEMIC EMERGENCY MEDICINE 2013; 20:592 596 2013 by the Society for Academic Emergency Medicine Acute abdominal pain is one of the most frequent complaints for which children and adolescents seek treatment in the emergency department (ED). Although more than 80,000 pediatric patients underwent appendectomy in the United States in 2009, there were more than 675,000 ED visits for abdominal pain. 1,2 As such, the vast majority of children who present with acute abdominal pain do not have appendicitis. Distinguishing between the diagnosis of appendicitis and other common pediatric ailments with overlapping symptoms remains a challenge, even with modern From the Division of Pediatric Surgery (JAN, TBL, MR) and Emergency Medicine (SD, MCP), Ann & Robert H. Lurie Children s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL. Received October 30, 2012; revision received December 20, 2012; accepted January 6, 2013. The authors have no relevant financial information or potential conflicts of interest to disclose. Supervising Editor: Richard Sinert, DO. Address for correspondence and reprints: Marleta Reynolds, MD; e-mail: MReynolds@luriechildrens.org. imaging modalities. As a result, the diagnosis of appendicitis is missed all too often. 3 5 The natural progression of acute appendicitis to perforation when not recognized and treated expeditiously results in increased morbidity and longer hospitalizations. 4,6 Prior studies have shown that between 5.9 and 27.6% of patients with acute appendicitis had missed opportunities to make the diagnosis earlier, resulting in an increase in the rate of perforation to 33.3% to 50.0% from a baseline of 20.3% to 28.0%. 7,8 That said, data on outcomes for patients with missed diagnoses of appendicitis are limited. The purpose of this study was to determine the fraction of children with acute appendicitis who had recent false-negative diagnoses and to analyze the effect of missed diagnosis on patient outcome. METHODS Study Design This was a retrospective chart review, performed for all pediatric patients who underwent laparoscopic appendectomies for suspected appendicitis from 2007 to 2010. Institutional review board approval (IRB# 2012-14806) ISSN 1069-6563 2013 by the Society for Academic Emergency Medicine 592 PII ISSN 1069-6563583 doi: 10.1111/acem.12144

ACADEMIC EMERGENCY MEDICINE June 2013, Vol. 20, No. 6 www.aemj.org 593 was granted, and informed consent requirements were waived. Study Setting and Population The study was performed in an urban tertiary care stand-alone children s hospital. Patients who underwent appendectomy as part of another procedure, not primarily for suspected appendicitis (e.g., appendectomy as part of a Ladd s procedure for malrotation), were excluded. Study Protocol The presence of appendicitis, as well as perforation or abscess, was determined by review of the surgical pathology, operative reports, or both. Patient factors including age, sex, race, ethnicity, insurance status, primary language, and patient body mass index were abstracted. A patient admitted or evaluated in the ED, discharged without a diagnosis of appendicitis, and then admitted and operated on for pathologically confirmed appendicitis within the next 3 days was considered to have a missed or false-negative diagnosis. Presenting signs and symptoms as well as any laboratory values and imaging studies obtained at initial presentation were reviewed for these patients. All subjective data points were confirmed by two independent reviewers. Outcomes for those children with missed diagnoses of appendicitis were compared to those of the remainder of the cohort. Outcomes of interest were length of hospital stay, perforation status, postoperative complications, related readmissions, and related reinterventions. Postoperative complications included wound infection, intraabdominal abscess, small bowel obstruction, granulation tissue, umbilical hernia, intraabdominal hematoma, infectious colitis, and urinary tract infection. Readmissions and reinterventions associated with any of these complications were considered related and included in the analysis. Data Analysis Body mass index-for-age percentile and weight-for-age percentile were calculated using Epi Info (Centers for Disease Control and Prevention, Atlanta, GA). Statistical analysis was performed using PASW Statistics 18 (IBM SPSS Statistics, Armonk, NY). Patient factors and outcomes were compared using chi-square analysis for categorical variables. Continuous variables were tested for normality using the Shapiro-Wilk test. Variables with significant variation from a normal distribution (p < 0.05) were reported as median (interquartile range [IQR]), rather than with a mean standard deviation [SD], for normally distributed variables). Continuous variables with nonnormal distributions were compared between groups using a nonparametric test (k-sample median test). A p-value < 0.05 was considered statistically significant. Factors associated with a missed diagnosis of appendicitis were assessed by multivariable logistic regression. For this analysis, all covariates with univariate p < 0.1 were included in the model. Model quality was evaluated through assessment of the c-statistic and the Hosmer-Lemeshow goodness-of-fit statistic. Covariates were assessed for significant multicollinearity by creating a correlation matrix for pairwise comparison of the covariates included in the model. These Pearson correlation results varied from 0.053 to 0.509, indicating that the covariates were not overly collinear. RESULTS A total of 816 patients who underwent appendectomy for suspected appendicitis were identified. Thirty-nine patients (4.8%) were admitted or evaluated in the ED for abdominal complaints within 3 days prior to their diagnoses of appendicitis and were considered to have missed diagnoses. Univariate analysis suggested a correlation of younger patient age, minority race or ethnicity, and Medicaid insurance coverage, with missed diagnoses of appendicitis. Multivariate analysis, however, revealed that demographic and patient factors were not predictive of missed diagnoses of appendicitis (Table 1). Presenting symptoms, diagnostic testing, and the discharge diagnoses given at the time of initial ED evaluation when the diagnosis of appendicitis was missed are shown in Table 2. Of note, only 12.8% of patients had documented right lower quadrant pain, only 35.9% presented with fever, and 25% had diarrhea. The most common misdiagnoses were acute gastroenteritis (43.6%), constipation (10.3%), emesis (10.3%), and abdominal pain not otherwise specified (NOS; 17.9%). The median time from the missed diagnosis to the admission for appendicitis was 28.3 hours (IQR = 17.0 to 39.6 hours). Median duration of symptoms at the time of missed diagnosis (1.0 day, IQR = 1.0 to 2.0 days) was similar to that at the time of appendectomy diagnosis in the nonmissed group (1.0 day, IQR = 1.0 to 2.0 days; p = 0.89). However, the cumulative symptom duration when the diagnosis of appendicitis was ultimately made in this missed group was significantly longer (3.0 days, IQR = 2.0 to 3.3 days; p < 0.001). Complete blood counts were obtained in 20.5% of missed patients and 95.4% of nonmissed patients. The median white blood count (910 9 cells/l) in the nonmissed group (15.6, IQR = 11.9 to 16.6) was similar to that of the missed group at the time of the missed encounter (14.0, IQR = 12.8 to 16.6; p = 0.29) and at the time of ultimate appendicitis diagnosis (15.1, IQR = 13.1 to 21.1; p = 0.74). Likewise, the mean absolute neutrophil count (910 9 cells/l) in the nonmissed group (13.0, IQR = 9.3 to 16.1) was similar to that of the missed group at the time of the missed encounter (12.2, IQR = 10.0 to 14.4; p = 0.29) and at the time of ultimate appendicitis diagnosis (13.0, IQR = 9.7 to 17.7; p = 1.00). Ultrasound was performed in 5.1% of missed patients and 34.6% of nonmissed patients. Computed tomography (CT) was performed in 2.6% of missed cases and in 40.2% of nonmissed cases. Outcomes for patients with and without missed appendicitis diagnoses are compared in Table 3. A missed diagnosis was associated with a longer median length of stay (5.8 days [IQR = 4.0 to 8.1 days] vs. 2.5 days [IQR = 1.8 to 4.6 days]; p < 0.001), higher rate of perforation (74.4% vs. 29.0%; p < 0.001), and higher complication rate (28.2% vs. 10.4%; p = 0.002). Complications in patients with and without missed appendicitis

594 Naiditch et al. MISSED APPENDICITIS IN CHILDREN Table 1 Predictors for Patients With a Missed Diagnosis of Appendicitis Univariate Multivariable Logistic Regression Predictor n (%) p-value Adjusted OR (95% CI) p-value Age quartile 1(<6.9 yr) 19/205 (9.3) <0.001 Referent 2 (6.9 9.6 yr) 11/201 (5.5) 0.60 (0.28 1.32) 0.21 3 (9.7 12.6 yr) 9/209 (4.3) 0.49 (0.22 1.13) 0.09 4 (12.7 18 yr) 0/201 (0.0) N/A Sex Male 22/476 (4.6) 0.80 Female 17/340 (5.0) Race/ethnicity White 2/186 (1.1) 0.009 Referent African American 2/55 (3.6) 3.05 (0.38 24.67) 0.30 Hispanic 35/534 (3.6) 3.20 (0.64 16.03) 0.16 Asian/other/unknown 0/41 (0.0) N/A Insurance Private 6/284 (2.1) 0.029 Referent Medicaid 33/529 (6.2) 1.42 (0.52 3.87) 0.50 Other/unknown 0/3 (0.0) N/A Primary language English 14/456 (3.1) 0.013 Referent Spanish 25/342 (7.3) 1.38 (0.63 3.02) 0.42 Other/unknown 0/18 (0.0) N/A Obesity Nonobese 21/481 (4.4) 0.76 Obese 17/321 (5.3) Unknown 1/14 (7.1) C-statistic = 0.773; Hosmer-Lemeshow p = 0.67. *Obesity = body mass index-for-age percentile or weight-for-age percentile > 85th percentile as defined by the Centers for Disease Control and Prevention for pediatric patients. diagnoses included wound infection (2.6% vs. 2.5%), intraabdominal abscess (20.5% vs. 4.9%), and small bowel obstruction (2.6% vs. 1.5%). All other individual complications occurred in fewer than three patients in either group. There was no difference in the rate of related hospital readmissions in patients who had missed diagnoses (23.1% vs. 13.0%; p = 0.07). Finally, patients with missed diagnoses had a higher rate of reintervention (20.5% vs. 6.2%; p = 0.003) through reoperation or percutaneous abscess drainage. DISCUSSION In this study, we demonstrate that 4.8% of pediatric patients who underwent appendectomy for acute appendicitis had recent prior encounters with false-negative diagnoses. At the time of initial evaluation, the patients history and physical examinations were not documented as classic for acute appendicitis, with acute gastroenteritis the most common erroneous diagnosis. Distinguishing factors for these patients with early appendicitis from the much larger cohort with nonsurgical abdominal complaints remains elusive. The rate of missed appendicitis diagnosis has been previously reported to range from 5.9% to 27.6%. An analysis done by Rothrock et al. 5 in 1990 revealed that the diagnosis of appendicitis was missed at initial presentation in 18.6% of 161 pediatric patients with appendicitis. Prior work from our institution in 1993 demonstrated that 7% of 87 pediatric patients treated for appendicitis Table 2 History, Evaluation, and Discharge Diagnoses of 39 Patients Who Were Discharged With Missed Diagnoses of Appendicitis Variable n (%) History Median symptom duration, days (IQR) 1.0 (1.0 2.0) Pain localized to RLQ 5 (12.8) Fever 14 (35.9) Emesis 27 (69.2) Diarrhea 10 (25.6) Evaluation Complete blood count 8 (20.5) Urinalysis 14 (35.9) CT 1 (2.6) Ultrasound 2 (5.1) Pediatric surgery consultation 3 (7.7) Discharge diagnosis Acute gastroenteritis 17 (43.6) Constipation 4 (10.3) Emesis 4 (10.3) Abdominal pain, NOS 7 (17.9) Other* 7 (17.9) Data reported as n (%) unless otherwise noted. NOS = not otherwise specified; RLQ = right lower quadrant. *Ovarian cyst (1), upper respiratory infection (1), urinary tract infection (2), streptococcal pharyngitis (1), Coxsackie A virus (1), fever, NOS (1). had prior ED visits where the diagnosis was missed. 8 Similarly, in a cohort of 916 patients of all ages with appendicitis, Graff et al. 7 found that 5.9% previously

ACADEMIC EMERGENCY MEDICINE June 2013, Vol. 20, No. 6 www.aemj.org 595 Table 3 Outcome of Patients Discharged Home With a Missed Diagnosis of Appendicitis Diagnosis Missed (n = 39) Diagnosis Not Missed (n = 777) p-value Outcome Median length of 5.8 (4.0 8.1) 2.5 (1.8 4.6) <0.001 stay, days (IQR) Appendicitis diagnosis Negative 0 25 (3.2) <0.001 Acute 8 (20.5) 453 (58.3) Gangrenous 2 (5.1) 74 (9.5) Perforated 29 (74.4) 225 (29.0) Any complication 11 (28.2) 81 (10.4) 0.002 Any related 9 (23.1) 101 (13.0) 0.07 readmission Any reintervention 8 (20.5) 48 (6.2) 0.003 Data are reported as n (%) unless otherwise noted. presented to the ED and were sent home with false-negative diagnoses. The 4.8% false diagnosis rate among 816 pediatric patients in our current study may represent a marginal improvement compared to these older series. Nonetheless, the rate at which this diagnosis is missed, even after patients present to the appropriate health care setting, remains unacceptably high and necessitates further quality improvement initiatives. Our results highlight the serious implications of missed opportunities to diagnose and treat appendicitis early in its course. There is a well-established relationship between delay in treatment of appendicitis and an increased rate of perforation with its sequelae. 4,9 13 Specifically, previous studies of treatment delay attributable to false-negative diagnoses have reported an increase in the rate of perforation from a range of 20% to 28%, to a range of 33% to 50%, compared to patients without missed opportunities for diagnosis. 7,8 Our data confirm this dramatic increase in the rate of perforation when the diagnosis of appendicitis was missed. We further examined the sequelae of these missed diagnoses and demonstrated an association with longer hospitalizations and higher rates of complications and reinterventions. The potential medical and societal implications of these findings are considerable. Delay in treatment for appendicitis can infrequently be attributed to a delay in diagnosis after the patient has made contact with the medical system due to diagnostic delay. Our findings highlight several potential areas for quality improvement efforts to reduce missed opportunities to diagnose appendicitis. Diagnostic studies were underutilized in our cohort at the time of missed diagnosis. Only 20.5% of children had complete blood counts and 5.1% underwent ultrasound evaluation. This paucity of diagnostic investigation may be attributable to the lack of classic findings of appendicitis, such as right lower quadrant pain, documented in only 12.2% of missed patients at initial presentation, and fever, documented in 36.6% of missed patients. Although CT scan has a high sensitivity for appendicitis, the long-term risks of ionizing radiation in the pediatric population must be taken under consideration when balancing the risk of the future malignancy with missing the diagnosis of appendicitis. 14 The reliance on diagnostic studies to rule in patients is, however, impractical when evaluating over 675,000 children presenting to the ED each year with abdominal complaints. Future studies should focus on developing clinical guidelines that improve clinical sensitivity and specificity for appendicitis in children. Such guidelines would be most useful to focus on input from history and physical findings before imaging or laboratory studies are considered. It is critical to provide clear discharge instructions to these patients whose early, atypical symptoms may persist or become more typical for appendicitis after discharge. There should be a defined plan for reevaluation if symptoms worsen or localize to the right lower quadrant. Observation should be considered for patients in whom the diagnosis is uncertain, especially when there is concern for the reliability of the parents, if the family lives far from a medical facility, or if the family lacks resources to bring the patient back for care. These extenuating circumstances can preclude the ability to return for reevaluation. Planning for short term reevaluation by a primary care doctor may help detect these missed patients earlier in their progression of the disease and aid in early referral back to the ED for surgical evaluation and to avoid perforation. LIMITATIONS We acknowledge limitations in this study inherent to its retrospective nature. The rate of missed diagnosis may be underestimated due to cases where either the initial missed encounter or the subsequent diagnosis and appendectomy occurred at another institution. Identifying factors associated with missed diagnoses in this retrospective study may be impaired by poor documentation regarding patient presentation in the medical chart. Patient review of symptoms was not standardized, and therefore data may be incomplete or inaccurate. Specific presenting symptoms (e.g., location of abdominal pain, the absence or presence of vomiting and diarrhea) may have been omitted. For the purposes of this study, any patient who had presented to the ED within 3 days of the eventual diagnosis of appendicitis was considered to have a missed diagnosis. This study is limited by our inability to definitively know whether the initial presentation was due to undiagnosed appendicitis. CONCLUSIONS We demonstrate that at least 4.8% of children who underwent appendectomy had missed opportunities for diagnosis of their conditions at earlier encounters. These misses were associated with longer hospitalization, higher rates of perforation and postoperative complications, and a higher need for postoperative interventions. Opportunities exist to further analyze this missed population with the potential to reduce the frequency of false-negative diagnoses. References 1. Agency For Healthcare Research and Quality. Health Cost and Utilization Project (HCUP). HCUPnet

596 Naiditch et al. MISSED APPENDICITIS IN CHILDREN National Statistics on Children. Available at:? twbch="./">http://hcupnet.ahrq.gov/hcupnet.jsp? Id=A51086BEF E712C11&Form=MAINSEL&JS=Y&Action=%3E%3E Next%3E%3E&_MAINSEL=For%20Children%20Only. Accessed Mar 18, 2013. 2. Agency For Healthcare Research and Quality. Health Cost and Utilization Project (HCUP). HCUPnet National Statistics on All ED Visits. Available at:?twbch="./">http://hcupnet.ahrq.gov/hcupnet.jsp? Id=00C2A34DB E28E828&Form=MAINSEL&JS=Y&Action=%3E% 3ENext%3E%3E&_MAINSEL=National%20Statistics. Accessed Mar 18, 2013. 3. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990;132: 910 25. 4. Pittman-Waller VA, Myers JG, Stewart RM, et al. Appendicitis: why so complicated? Analysis of 5755 consecutive appendectomies. Am Surg. 2000;66: 548 54. 5. Rothrock SG, Skeoch G, Rush JJ, Johnson NE. Clinical features of misdiagnosed appendicitis in children. Ann Emerg Med. 1991;20:45 50. 6. Nwomeh BC, Chisolm DJ, Caniano DA, Kelleher KJ. Racial and socioeconomic disparity in perforated appendicitis among children: where is the problem? Pediatrics. 2006;117:870 5. 7. Graff L, Russell J, Seashore J, et al. False-negative and false-positive errors in abdominal pain evaluation: failure to diagnose acute appendicitis and unnecessary surgery. Acad Emerg Med. 2000;7:1244 55. 8. Reynolds SL. Missed appendicitis in a pediatric emergency department. Pediatr Emerg Care. 1993;9:1 3. 9. Brender JD, Marcuse EK, Koepsell TD, Hatch EI. Childhood appendicitis: factors associated with perforation. Pediatrics. 1985;76:301 6. 10. Eldar S, Nash E, Sabo E, et al. Delay of surgery in acute appendicitis. Am J Surg. 1997;173:194 8. 11. Korner H, Sondenaa K, Soreide JA, et al. Incidence of acute nonperforated and perforated appendicitis: age-specific and sex-specific analysis. World J Surg. 1997;21:313 7. 12. Von Titte SN, McCabe CJ, Ottinger LW. Delayed appendectomy for appendicitis: causes and consequences. Am J Emerg Med. 1996;14:620 2. 13. Williams N, Bello M. Perforation rate relates to delayed presentation in childhood acute appendicitis. J R Coll Surg Edinb. 1998;43:101 2. 14. Doria AS. Optimizing the role of imaging in appendicitis. Pediatr Radiol. 2009; 39(Suppl 2):S144 8.