Outcomes of Nonoperative ManagementRichard G. Bachur, MD, Susan C. Lipsett, MD,of Michael Uncomplicated C. Monuteaux, ScD

BACKGROUND AND OBJECTIVES:Appendicitis abstract

Nonoperative management (NOM) of uncomplicated pediatric appendicitis has promise but remains poorly studied. NOM may lead to an increase in resource utilization. Our objective was to investigate the trends in NOM for uncomplicated appendicitis and study the relevant clinical outcomes including subsequent appendectomy, METHODS: complications, and resource utilization. Retrospective analysis of administrative data from 45 US pediatric hospitals. Patients <19 years of age presenting to the emergency department (ED) with appendicitis between 2010 and 2016 were studied. NOM was defined by an ED visit for uncomplicated appendicitis treated with antibiotics and the absence of appendectomy at the index encounter. The main outcomes included trends in NOM among children with uncomplicated appendicitis and frequency of subsequent diagnostic imaging, ED visits, hospitalizations, RESULTS: and appendectomy during 12-month follow-up. 99001 children with appendicitis were identified, with a median age of 10.9 years. Sixty-six percent were diagnosed with nonperforated appendicitis, of which 4190 (6%) were managed nonoperatively. An increasing number of nonoperative cases were observed over 6 years (absolute difference, +20.4%). During the 12-month follow-up period, NOM patients were more likely to have the following: advanced imaging (+8.9% [95% confidence interval (CI) 7.6% to 10.3%]), ED visits (+11.2% [95% CI 9.3% to 13.2%]), and hospitalizations (+43.7% [95% CI 41.7% to 45.8%]). Among patients managed nonoperatively, 46% had a CONCLUSIONS: subsequent appendectomy. A significant increase in NOM of nonperforated appendicitis was observed over 6 years. Patients with NOM had more subsequent ED visits and hospitalizations compared with those managed operatively at the index visit. A substantial proportion of patients initially managed nonoperatively eventually had an appendectomy.

Whanw t’s K o n on This Subject: Nonoperative Division of Emergency Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts management (NOM) of uncomplicated appendicitis has proven to be successful in select cases but remains Dr Bachur conceived and designed the study, analyzed and interpreted the data, and drafted and poorly studied. Although success rates may approach critically revised the manuscript; Dr Lipsett interpreted the data and drafted and critically revised 70% in limited prospective studies, premature adoption of the manuscript; Dr Monuteaux designed the study, acquired the data, analyzed and interpreted NOM may have unintended consequences on subsequent the data, and drafted and critically revised the manuscript; and all authors approved the final resource utilization. manuscript as submitted. Dr Monuteaux had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. What This Study Adds: Among patients with uncomplicated appendicitis, NOM was associated with DOI: https://​doi.​org/​10.​1542/​peds.​2017-​0048 an increase in subsequent emergency department visits Accepted for publication Apr 11, 2017 and hospitalizations compared with those managed operatively. During 1-year follow-up, 46% of those managed Address correspondence to Richard G. Bachur, MD, Division of Emergency Medicine, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: [email protected] nonoperatively had a subsequent appendectomy.

To cite: Bachur RG, Lipsett SC, Monuteaux MC. Outcomes of Nonoperative Management of Uncomplicated Appendicitis. Pediatrics. 2017;140(1):e20170048

Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 140, number 1, July 2017:e20170048 Article Appendectomy has been the hypothesize that patients managed appendicitis with peritonitis or standard practice for uncomplicated nonoperatively will have increased abscess (540.0, 540.1; K35.2, pediatric appendicitis across the rates of subsequent emergency K35.3). Children with any chronic33 United States. Although considered department (ED) visits and Datacomorbidities Assumptions were and excluded Data Integrity. routine and safe, appendectomy has hospitalizations as compared with a recognized risk of complications those with primary appendectomy. including postoperative abdominal As a consequence of the option Without clinical information, we wall infections, intraperitoneal for NOM, we also speculate that made the following assumptions: infections, and bowel obstruction1,2​ the diagnosis of appendicitis will diagnostic studies ordered for secondary to adhesions. ‍ For increase in the absence of a histologic ED patients were performed for those with complicated appendicitis standard. the purpose of evaluation of the associated with abscess or phlegmon, Methods primary diagnosis. For evaluating the initial antibiotic treatment with a Data Source and Design frequency and outcomes of NOM, we delayed interval appendectomy3,4​ has classified patients as receiving NOM been shown to be effective,​ ‍ when 3 conditions were satisfied: (1) although the– need for the the patient had an ED encounter with This is a retrospective study using subsequent 5appendectomy8 has been the primary diagnosis of appendicitis data obtained from the Pediatric questioned. ‍‍ (nonperforated appendicitis Health Information System (PHIS), diagnostic codes), (2) parenteral Nonoperative management (NOM) an administrative database that – antibiotics were administered, and of acute appendicitis has been the contains inpatient, ED, ambulatory, (3) no appendectomy procedure code subject of recent investigations and observation encounter level was associated with the initial visit. and interest. Although previously data from 47 not-for-profit, tertiary To avoid the possibility of including practiced in remote locations care pediatric hospitals in the 9 10 ’ patients with a recent complication and during wartime,​ Coldrey United States. These hospitals are of an appendectomy as an index case in 1959 published the first large affiliated with the Children s Hospital of newly diagnosed appendicitis, we series of 471 adult patients treated Association (Overland Park, KS). Data removed any patients with a previous conservatively with antibiotics – quality and reliability are assured ’ diagnosis of appendicitis or who had alone. The more recent interest has through a joint effort between the 11 18 a previous appendectomy (on the grown from modern adult trials. ‍ Children s Hospital Association basis of available data for a minimum As demonstrated in a 2016 meta- and participating hospitals. For the 19 of 12 months before their ED visit). analysis,​ the 1-year success rate purposes of external benchmarking, of NOM of acute appendicitis in participating hospitals provide Data integrity was judged by testing adults is 63% without increased discharge or encounter data the following conditions: (1) all complications among treatment– including demographics, diagnoses, patients with acute nonperforated failures. Pediatric data are limited–20 23 and procedures. Forty-five of these appendicitis had an appendectomy to a 4 retrospective studies,24 ​27‍ hospitals also submit resource procedure or were treated with 4 prospective– case series,​ ‍ ‍ 4 utilization data (eg, pharmaceuticals, parenteral antibiotics at the index prospective28 31 comparative pediatric 32 imaging, and laboratory) into PHIS. visit (98.6%), and (2) all patients studies,​ ‍‍ and 1 randomized trial Data are deidentified at the time of with perforated appendicitis were with a reported 1-year success rate of data submission. administered antibiotics (99.3%). 58% to 79%. Patients with acute appendicitis that We investigated all children <19 were discharged from the ED without Despite the limited pediatric years of age with a primary diagnosis a parenteral dose of antibiotics would data, growing interest in medical of appendicitis in association with an be missed from the analysis, although management and the trend toward ED encounter from January 1, 2010, all the previous pediatric studies of shared decision making with through June 30, 2016. An encounter International NOM included at least a single dose informed patients and parents was classified as an appendicitis case – – Classification of Diseases of parental antibiotics before oral has led to early, and potentially if any of the following 20,21,​ 23​ 27,29​ 32 Aantibioticsnalytic Plan. ‍ ‍ ‍ ‍ ‍ ‍ ‍ premature, adoption of nonoperative version 9 care. Herein, we sought to determine or 10 codes were assigned as the NOM Trends the frequency and outcomes primary diagnosis from the ED visit: of nonoperative treatment of ICD-9 540.0, 540.1, 540.9, 541, or uncomplicated appendicitis at major 542; ICD-10 K35.80, K35.89, K36, The frequency of NOM was displayed US pediatric institutions by using a or K37. Perforated appendicitis over time as a proportion of large administrative database. We was defined by diagnostic codes: nonperforated appendicitis cases. Downloaded from www.aappublications.org/news by guest on September 23, 2021 2 Bachur et al TABLE 1 Study Population (N = 99 001) Age, y, median (interquartile 10.9 (8.1 to 13.8) To test for trends of NOM, we perforation (subsequent visit). range) estimated a multivariable logistic Failure of antibiotics during the Sex (male) 59 818 (60.4) regression model of nonoperative initial visit, defined in previous Race White 65285 (65.9) care with 3-month time blocks as studies as lack of improvement– African American 7467 (7.5) the independent variable. A robust or worsening signs during initial 19,28​ 32 Asian American 2103 (2.1) variance estimator was used to inpatient course,​ ‍ ‍ ‍ could not Other 18 847 (19.0) accommodate the correlation be studied with this data set since Missing 5299 (5.4) resulting from the clustering of the exact time of the appendectomy Ethnicity patients within hospitals. during the initial hospitalization was Latino 34 049 (34.4) Not Latino 56881 (57.5) not available. However, any patient We compared demographic variables, Unknown 8071 (8.2) with appendicitis that was discharged a diagnostic imaging at the index Index visit imaging after the index visit (whether from Ultrasound 48493 (49.0) visit, and duration of hospitalization ED or inpatient unit) but returned CT 24 913 (25.2) among patients with nonperforated for appendectomy was considered MRI 768 (0.8) appendicitis managed with primary Diagnoses a failure of NOM. We investigated Frequencyappendectomy of the and Diagnosis nonoperative of care. Perforated appendicitis 33 279 (33.6) predictors of having a subsequent Appendicitis Nonperforated 65 712 (66.4) appendectomy (among those with appendicitis nonperforated appendicitis managed Appendectomy at index 61 522 (93.6) nonoperatively) by estimating a visit No appendectomy at 4190 (6.4) To assess the frequency of diagnosis, model with age, sex, race, initial index visit the number of patients with length of stay (LOS), and total appendicitis was displayed over Values in table represent frequency (%) except where doses of parenteral antibiotics as noted. time and stratified by hospital covariates. Assuming that hospitals a Restricted to imaging of the abdominal region. utilization of NOM (based on 2016 with more experience with NOM data). We calculated the proportions might have lower rates of perforation of nonperforated cases managed or subsequent appendectomy, with primary appendectomy, we tested the correlation of these appendicitis, and of these, 4190 (6%) nonperforated cases managed outcomes with the hospital-level were managed nonoperatively (Fig 1). nonoperatively, and cases of Generalrates of ConsiderationsNOM. Trends in NOM over the study period appendiceal perforation to identify are shown in Fig 2. NOM significantly Outcomesany trends of in NOM diagnostic frequency. increased over the study period α All statistical tests were 2-tailed (absolute difference +20.4%, test for and was set at .05. All analyses linear trend odds ratio (OR) [95% To investigate relevant outcomes, were conducted with the statistical confidence interval (CI)] = 1.13 [95% we reviewed the fraction of software package Stata 13.1 CI 1.04 to 1.23]). patients having 12 months of (StataCorp, College Station, TX). follow-up available (index visit The study was approved by the During the study period, 54958 before July 2015). Five relevant institutional review board and the children had 12 months of follow-up outcomes were assessed among administrators of the PHIS database. available and were included in patients managed nonoperatively: In accordance with PHIS policies, the the analysis of 1-year outcomes. (1) subsequent ED visits with a identities of the institutions were not There was an overall increase potentially related diagnosis (eg, reported. in the number of appendicitis appendicitis, abdominal pain, Results intestinal obstruction, vomiting, cases as shown in Fig 3, stratified diarrhea, dehydration, colitis); Study Sample by hospital-level utilization of NOM; hospitals with >40% NOM (2) subsequent hospitalizations related to appendicitis; (3) advanced had the largest increase in the imaging studies of the abdomen 99001 children with appendicitis diagnosis of appendicitis (+54.5%). after the index visit; (4) frequency were identified during the study Increases in NOM corresponded to of subsequent appendectomy after period. Demographics and clinical decreases in primary appendectomy discharge from the index visit; (5) characteristics are displayed in Table (Supplemental Fig 4). The 1. The sample was predominantly frequencies of specific antibiotics proportion of patients that converted from an initial nonperforated male (60%) with a median age of 10.9 administered during the initial NOM appendicitis diagnosis (index visit) years. At the index visit, 65712 (66%) encounter are listed in Supplemental to complicated appendicitis with were diagnosed with nonperforated Table 4. Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 140, number 1, July 2017 3 − − − but less likely to have a MRI ( 0.3% [95% CI 0.5 to 0.1]).

During the 12 months after the index visit, nonoperative patients were more likely to have additional advanced imaging (absolute risk difference +8.9% [95% CI 7.6% to 10.3%]). Subsequent ED visits and hospitalizations occurred more frequently for those managed nonoperatively (+11.2% [95% CI 9.3% to 13.2%] and +43.7% [95% CI 41.7% to 45.8%], respectively). Among children managed nonoperatively, 46% had a subsequent appendectomy. The median time to subsequent – appendectomy for NOM patients was 1 day (interquartile range 1 4 days); if the analysis is limited to NOM patients admitted to the hospital at the index visit (ie, removing patients nthat were discharged directly from the ED after parenteral antibiotics, = 942), the median time to – subsequent appendectomy was 52 FIGURE 1 days (interquartile range 33 94 Study sample of appendicitis cases from 45 hospitals included in the PHIS database from 2010 to days). Younger age, having a CT study 2016. at the initial visit, and more doses of parenteral antibiotics at the index visit were predictive of subsequent appendectomy (age in years OR 0.93 [95% CI 0.90 to 0.97], CT 3.87 [95% CI 1.91 to 7.86], antibiotic doses 1.58 [95% CI 1.03 to 2.44]), whereas an initial ultrasound at the index visit (OR 1.58 [95% CI 0.34 to 7.47]), male sex (OR 1.00 [95% CI 0.87 to 1.16]), and LOS at the initial visit (OR 0.41 [95% CI 0.16 to 1.08]) were not predictive of subsequent appendectomy. Additionally, rates FIGURE 2 of subsequent appendectomy or Proportion of cases of appendicitis managed nonoperatively from 2010 to 2016 at 45 US pediatric perforation did not correlate with hospitals. the proportion of patients managed nonoperatively in a hospital-level Operative Versus Nonoperative analysis. Management Among Children With Nonperforated Appendicitis groups have similar age and sex. Discussion Median LOS was 1 day for both. Nonoperative patients were more The characteristics and outcomes likely at the initial visit to have an In this observational study based of children managed with primary ultrasound (+9.0% [95% CI 7.4% to on administrative data, medical appendectomy and nonoperative 10.5%]) and computed tomography management of nonperforated care are displayed in Table 2. Both (CT) (+3.7% [95% CI 2.4 to 5.0]) appendicitis is increasing at large US Downloaded from www.aappublications.org/news by guest on September 23, 2021 4 Bachur et al pediatric hospitals, including nearly a quarter of cases in 2016. Outcomes included subsequent appendectomy in 46% of hospitals and appendiceal perforation in 14%. The short median time to subsequent appendectomy for NOM patients was influenced mostly by patients discharged from the ED after parenteral antibiotics. For those managed nonoperatively, there was a substantial rate of subsequent diagnostic imaging (absolute risk difference +8.9%), ED revisits (+11.2%), and subsequent hospitalization (+43.7%). Potentially FIGURE 3 as a consequence of the option for Trends in the number of nonperforated appendicitis cases among PHIS hospitals over the study nonoperative care, the diagnosis of period. Hospitals are stratified by the proportion of cases with NOM (on the basis of the proportion of NOM cases in 2016). appendicitis is increasing among hospitals utilizing NOM. For the last century, urgent appendectomy has been the with medical management. As compared with the adult standard of care for uncomplicated Overall treatment efficacy in the literature, pediatric data are more appendicitis because of concern for nonoperative group over 1 year of limited, and a meta-analysis has appendiceal rupture without prompt follow-up was 63%, with only 6.4% not been possible because of the surgical treatment. Recent progress of patients developing complicated heterogeneity of the treatment with the laparoscopic approach has – appendicitis. As stated by the strategies and study end points. reduced the length of hospitalizations 34 38 authors, who used standard criteria Among the 5 prospective studies, 4 and recovery time. ‍ Despite the “ ” – for systematic reviews, each of were nonrandomized comparative procedure being routine and safe, “ ” 28 31 the studies had serious risks of trials,​ ‍ ‍ and 1 was a randomized complications including surgical 32 bias with overall low quality of trial by Svensson et al. The site infections, intraabdominal evidence. All 5 studies were subject prospective pediatric trials are infections, and peritoneal to enrollment bias. Three of the summarized in Table 3. Each adhesions occur in 3% of cases of 1,39,​ 40​ studies required diagnostic imaging study defined early treatment nonperforated appendicitis. ‍ ‍ 12,15,​ 18​ for enrollment ‍ ‍ whereas success differently, with varying NOM of appendicitis is not new, but 13,17​ imaging was optional in 2 studies ‍ ; duration of parenteral antibiotics the surge in interest has grown from the authors acknowledge that and inconsistent determinants the success of antibiotic treatment of – the studies that did not require of treatment failure prompting complicated appendicitis and other 41 44 imaging would not properly identify appendectomy. For many studies, intraabdominal conditions,​ ‍‍ the complicated appendicitis or patients conversion to appendectomy was convenience of reliable diagnostic with an appendicolith, which are indicated by a lack of improvement imaging to identify appendicitis and known to be risk factors for failure or persistently elevated monitor for complications, and the 16,18,​ 19​ with nonoperative care. ‍ ‍ Rollins inflammatory markers, whereas availability of oral broad-spectrum 19 et al emphasized the 39% risk others continued antibiotics in antibiotics. Additionally, the reduction for complications (defined the absence of signs of peritonitis. invigorated focus on quality-of-life by treatment arm) for nonoperative One study used repeat ultrasounds outcomes and cost has further driven 31 patients without any difference to monitor for complications. the debate over nonoperative care 45 in LOS between the 2 groups. The All the comparative studies have versus automatic appendectomy. observation that patients who failed significant risk of enrollment bias Nonoperative treatment of nonoperative treatment had similar because of varying diagnostic criteria uncomplicated appendicitis in adults rates of complicated appendicitis and treatment selection (often by was summarized in a 2016 meta- as those treated with primary parent or surgeon choice). The early analysis19 performed by Rollins appendectomy was considered treatment success of the prospective et al. Five studies with 1430 supportive of an initial nonoperative studies ranged from 58% to 99% subjects included 727 cases approach. for the nonrandomized trials and Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 140, number 1, July 2017 5 TABLE 2 Management and Outcomes of Children With Nonperforated Appendicitis (N = 65 712) Operative: Nonoperative: n = 4190 Δ, 95% CI 92% for the randomized trial; this n = 61 522 range of effectiveness likely reflects Index Visit the variation in patient selection, Age, y 11.4 [8.8 to 14.2] 11.4 [8.6 to 14.2] −0.07 (−0.23 to 0.10) varying treatment regimens, and Sex (male) 37 657 (61.2) 2564 (61.2) −0.0 (−1.5 to 1.5) the definition of treatment failure. Admitted 61 522 (100) 2416 (57.7) −42.3 (−43.8 to −40.8) The 1-year appendectomy rates LOS, d 1.0 [1.0 to 2.0] 1.0 [1.0 to 1.0] Not estimated among those studies ranged from LOS (among admitted), d 1.0 [1.0 to 2.0] 1.0 [1.0 to 1.0] Not estimated Doses of parenteral 2.0 [1.0 to 3.0] 2.0 [1.0 to 2.0] Not estimated 58% to 79%. In the randomized trial, antibiotics 38% (9/24) of the nonoperative Ultrasound 29 871(48.6) 2411 (57.5) 9.0 (7.4 to 10.5) patients had a subsequent CT 12 066 (19.6) 976 (23.3) 3.7 (2.4 to 5.0) appendectomy; interestingly, 5 MRI 477 (0.8) 19 (0.5) −0.3 (−0.5 to −0.1) of the patients presented months Follow-up period (12-mo period n = 52 731 n = 2227 after index visit)a after initial successful treatment Ultrasound 969 (1.8) 120 (5.4) 3.6 (2.6 to 4.5) with recurrent abdominal pain, and CT 834 (1.6) 183 (8.2) 6.6 (5.5 to 7.8) all had varying degrees of fibrosis MRI 30 (0.06) 5 (0.22) 0.17 (−0.03 to 0.37) without inflammation. In the current No. diagnostic imaging investigation, 46% of children studies 0 51 143 (97.0) 1961 (88.1) −8.9 (−10.3 to −7.6) managed with nonoperative care 1 1133 (2.2) 154 (6.9) 4.8 (3.7 to 5.8) had a subsequent appendectomy; ≥2 455 (0.9) 112 (5.0) 4.2 (3.3 to 5.1) similar to the recently published No. ED visits 0 42 909 (81.4) 1562 (70.1) −11.2 (−13.2 to −9.3) comparative trial by Caruso31 et al (the largest in pediatrics),​ failures 1 6791 (12.9) 489 (22.0) 9.1 (7.3 to 10.8) ≥2 3031 (5.8) 176 (7.9) 2.2 (1.0 to 3.3) occurred relatively early. We also No. hospitalizations noted that 14% of the current study 0 49 516 (93.9) 1117 (50.2) −43.7 (−45.8 to −41.7) patients were ultimately diagnosed 1 2721 (5.2) 1036 (46.5) 41.4 (39.3 to 43.4) with perforated appendicitis, which ≥2 494 (0.9) 74 (3.3) 2.4 (1.6 to 3.1) is higher than reported in the limited Subsequent appendectomy NA 1032 (46) NA Time to appendectomy in NA 1 [1 to 4] NA pediatric comparative studies28, that31​ daysb show a rate of 2.5% to 2.7%. This New diagnosis of perforation NA 313 (14.0) NA increase in perforation rate may be appendicitis related to the differences in patient Values in table represent frequency (percent) or median [interquartile range]. All imaging data are restricted to studies selection at the onset or treatment, of the abdominal region. NA, not applicable. a Restricted to patients with an index visit on or before July 1, 2015, to allow for a full year of follow-up surveillance. inadequate antibiotic treatment b Calculated as number of days from initial admission date. regimens, patient noncompliance, or limitations of measuring this outcome by using administrative data. In support of the possibility of complications of NOM. We have for serial examinations, obtaining a inadequate treatment regimens, only several concerns related to the CT, or proceeding with laparoscopy. 58% of NOM patients were admitted observed increase in nonoperative Although we do not have enough to the hospital (after parenteral care before more rigorous studies. clinical detail to fully understand our antibiotics in the ED), and only 25% First, without clear eligibility findings, we did observe an increase of cases had more than 2 doses of criteria or a diagnostic standard, we in patients with an appendicitis parenteral antibiotics. anticipate a less disciplined approach diagnosis, especially in hospitals to the diagnosis of appendicitis, utilizing NOM more frequently. As The significant heterogeneity of the leading to the overuse of antibiotics nonoperative treatment becomes data for the nonoperative treatment for presumed appendicitis. Currently, more widespread, the consequences demands well-designed comparative ultrasound is the primary imaging of treating a patient with suspected effectiveness trials that have clear modality despite its inferior (but unproven) appendicitis diagnostic criteria, definitions for performance to CT and46 high rate with antibiotics would likely be early failure, and a standardized of equivocal results. With the considered more acceptable than response to recurrent episodes of convenient and low-risk option for a negative appendectomy. Second, abdominal pain. Although there medical management, clinicians faced although the preliminary (albeit are definitions for complications of with indeterminate ultrasounds biased) data indicates that 58% to operative care, each of the previous may have a tendency to treat with 79% of children with uncomplicated studies had various definitions for antibiotics rather than admitting appendicitis might be successfully Downloaded from www.aappublications.org/news by guest on September 23, 2021 6 Bachur et al Group Secondary Outcomes stay (total cost similar between groups) either group 4.7 out of 5) appendectomy with extended follow-up $4130) quality-adjusted life months vs 0.854 – 0.856) 21 d); returned to school faster (3 vs 5 d); similar quality of life scores, incurred longer LOS (median 37 vs 20 h) conservative treatment: 4.9 vs 7.9 d Nonoperative Versus Operative Lower cost for initial inpatient No significant complications in Lower overall satisfaction (4.4 vs 71% managed without Higher utility (0.863 – 0.884 62 Longer LOS (median 52 vs 35 h) 79 Similar LOS (6.6 vs 6.5 d) 71 Lower overall cost ($2771 vs 76 Fewer disability days (median 8 vs 58 Mean LOS shorter for No appendectomy at 1-y follow-up, % 92 99 88 95 58 Immediate With NOM, % Success During Initial Treatment Initial Treatment Outcomes without significant complications; LOS, complications, recurrence within 1 y nonoperative care during initial hospitalization; patient satisfaction operative therapy, recurrence disability days, missed school, hospital LOS, quality of life patient and parent LOS, complications Primary and Secondary Resolution of symptoms Success rate of Progression to 30 d success rate; Early success at 1 wk, Cost-utility analysis Protocol 48 h of IV antibiotic followed by 8 d oral antibiotic until CRP normalized and patient clinically improved; no mention of oral antibiotics doses of IV antibiotics, followed by 7 d oral antibiotic 24 h of IV antibiotic; total 10 d oral antibiotic 72 h of IV antibiotic followed by 5 d oral antibiotic Minimum controls (complicated) (uncomplicated) Patient Sample Nonoperative 65 operative as 165 operative 78 nonoperative IV antibiotics 197 nonoperative 26 operative 86 operative 50 operative (>75% 3 , nonruptured 3 Design 000/mm

rials for NOM of Uncomplicated Appendicitis 000/mm

neutrophils), CRP > 3 mg/ dL; ultrasound positive or nonvisualized appendix appendicitis by ultrasound or CT, appendicitis by ultrasound or CT, no appendicolith Age 5 – 16 y with nonperforated appendicitis by ultrasound or CT, with or without appendicolith complicated appendicitis all underwent early surgery, those with uncomplicated appendicitis started nonoperative care nonruptured appendicitis by with or without ultrasound or CT, appendicolith clinical diagnosis of acute uncomplicated appendicitis (all ultrasound), with or without fecalith, but with no concern for perforation or abscess count < 18 4, WBC > 12 Randomized controlled trial 24 nonoperative Minimum Nonrandomized; caregiver choice Nonrandomized; caregiver choice 24 nonoperative Minimum of 2 Nonrandomized; caregiver choice 37 nonoperative Minimum Nonrandomized; patients with Age 5 – 15 y, <48 h of pain, Age 5 – 18 y, <48 h of pain, with Age 7 – 17 y, <48 h of pain, WBC Diagnosis of appendicitis: PAS > 32 30 l l 28 l 29 31 l l  Summary of Prospective Pediatric T

3 Year Study ABLE 2015 Svensson et a 2016 Caruso et a CRP, C-reactive protein; IV, intravenous; PAS, Pediatric Appendicitis Score; WBC, white blood cell. C-reactive protein; IV, CRP, T 2015 Tanaka et a 2016 Hartwich et a 2016 Minneci et a

Downloaded from www.aappublications.org/news by guest on September 23, 2021 PEDIATRICS Volume 140, number 1, July 2017 7 Conclusions treated without surgery, we have no of appendicitis before care at the knowledge about the cost and anxiety major pediatric hospital. However, By using administrative data from related to subsequent episodes of we have no reason to suspect major major pediatric institutions, we abdominal pain with associated shifts over the study period in types observed a significant increase medical visits, repeat diagnostic of referrals or care before transfer. in the number of patients with imaging, and repeated antibiotic The number of patients transferred nonperforated appendicitis treated treatments. Finally, without a to these institutions would generally nonoperatively. Patients with NOM standardized approach founded in be small and would not significantly had more repeat ED visits and structured prospective studies, we influence the observed rate of hospitalizations compared with will be unable to optimally advise subsequent appendectomy or the those managed operatively at the patients and caregivers on treatment increase in repeat ED visits, diagnostic index visit. Forty-six percent of options. imaging, or hospitalizations seen those treated nonoperatively had a This investigation is limited by with NOM patients. With regard subsequent appendectomy within the use of administrative data to to nonoperative treatment, early the first year. During the study determine clinical management and failures during initial hospitalization period, the number of patients being outcomes. We relied on assumptions cannot be accurately distinguished diagnosed with appendicitis appears that diagnostic coding has an from patients with a primary to be increasing, potentially as a accurate clinical correlate. Previous appendectomy (and potentially could consequence of the option of NOM. investigations on appendicitis underestimate the use of NOM and These findings have implications outcomes using this data source have NOM failures). Similarly, although for the adoption of nonoperative not standard practice and not been validated47 with medical record treatment and should inform future review. Additionally, the current previously described, patients could studies. Finally, as this analysis study population mimics previous be theoretically discharged with a relied on administrative data investigations with respect to age plan for a scheduled appendectomy, with assumptions about a clinical and sex distribution of appendicitis which would lead to the appearance of correlate, these conclusions will cohorts. The large data set allows failure of conservative management. need further validation with large trends to be observed, but patient- We assumed that NOM patients prospective clinical studies. discharged and returning for an level data would be necessary to Abbreviations accurately determine reasons for appendectomy would imply a specific management and better treatment failure as described in a explain clinical causes of repeat visits, recently released article by Talan 48 CI: confidence interval subsequent diagnostic imaging, or et al. Finally, the administrative CT: computed tomography delayed appendectomies. Additionally, data only tracks patients presenting ED: emergency department we acknowledge that the hospitals to the same institution; therefore, LOS: length of stay included in this analysis often serve subsequent visits or procedures NOM: nonoperative management as referral centers, and we cannot may be missed, including non-ED OR: odds ratio account for imaging or management ambulatory visits during which PHIS: Pediatric Health before arrival at the ED; it is possible additional care may have been Information System that patients had previous treatment provided. PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2017 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: Dr Bachur holds a patent for biomarkers of appendicitis (US 8535891 B2) and has had research support from Astute Medical, Inc (San Diego, CA); and Drs Lipsett and Monuteaux have indicated they have no potential conflicts of interest to disclose.

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