In patients with appendicitis, the risk of perforation increases with time from onset of symptoms. We sought to determine if time from emergency department (ED) physician evaluation until operative intervention is independently associated with appendiceal perforation (AP) in children.
We conducted a planned secondary analysis of children aged 3 to 18 years with appendicitis enrolled in a prospective, multicenter, cross-sectional study of patients with abdominal pain (<96 hours). Time of initial physical examination and time of operation were recorded. The presence of AP was determined using operative reports. We analyzed whether duration of time from initial ED physician evaluation to operation impacted the odds of AP using multivariable logistic regression, adjusting for traditionally suggested risk factors that increase the risk of perforation. We also modeled the odds of perforation in a subpopulation of patients without perforation on computed tomography.
Of 955 children with appendicitis, 25.9% (n = 247) had AP. The median time from ED physician evaluation to operation was 7.2 hours (interquartile range: 4.8–8.5). Adjusting for variables associated with perforation, duration of time (≤ 24 hours) between initial ED evaluation and operation did not significantly increase the odds of AP (odds ratio = 1.0, 95% confidence interval, 0.96–1.05), even among children without perforation on initial computed tomography (odds ratio = 0.95, 95% confidence interval, 0.89–1.02).
Although duration of abdominal pain is associated with AP, short time delays from ED evaluation to operation did not independently increase the odds of perforation.
Comments
Author Response to Commentary
Dear Editor,
We read with interest the comments by Dr. Bonadio regarding our recently published study [Pediatrics June 2017, 139 (6) e20160742; DOI: 10.1542/ peds.2016-0742] and respond accordingly:
1) Dr. Bonadio recommended we exclude patients who had no imaging or ultrasonography only. Although our main results include all patients with appendicitis regardless of imaging modality, we performed a sensitivity analysis among a subset of children who did not have perforation on computed tomography and found no association between time from ED evaluation to surgery and perforation (Table 3, OR = 0.95, 95% CI 0.89-1.02, n=403).
2) While pathology reports were used to determine the presence of appendicitis, only surgical reports were used to determine perforation. We used a standardized manual of operations to extract data regarding perforation from the surgical report only, using language agreed upon by expert clinicians, including emergency medicine physicians and surgeons.
3) Regarding radiologic criteria for diagnosis of appendicitis and perforation, our standardized definitions of appendicitis detected by computed tomography and ultrasonography have been reported.1 Perforated appendicitis was considered present on computed tomography or ultrasonography if the attending radiologist’s note specified that the findings were consistent with appendiceal perforation, indicated “likely” or “possible” perforated appendicitis, or mentioned the key phrases “developing abscess in the pelvis, evidence for a discrete drainable collection or presence of a well formed abscess”.
4) We recognize in the manuscript that we did not collect information about timing of administration of intravenous antibiotics. However, the majority of sites (7/9) reported administration of antibiotics routinely to patients with non-perforated appendicitis in the ED, reducing the likelihood of significant confounding.
Our study methodology differed significantly from several prior publications. We excluded patients who underwent surgery > 24 hours after ED evaluation since diagnostic uncertainty may have been a primary factor rather than a short delay in operative intervention. In contrast, in the study by Bonadio et al,2 nearly one third (17/54) of patients who suffered perforation, went to the operating room after 24 hours, substantially influencing their findings. Notably, no patients in their study experienced perforation within 9 hours. In our experience, most children who undergo an appendectomy, will do so in less than 24 hours from their index ED visit. We also note that we assessed duration of symptoms prior to ED presentation in 12 hour increments (versus days in the Bonadio study2 and not at all in the Meltzer study3) and achieved reasonable inter-rater agreement for this variable,4 which could account for our ability to detect an association between duration of symptoms prior to ED evaluation and perforation.
Finally, a newly released study using data from 23 children’s hospitals in the Pediatric National Surgical Quality Improvement Program (PNSQIP) found no significant associations between time from ED presentation and the risk of complicated appendicitis or post-operative complications. 5 Collectively, the data from our multi-center study as well as the PNSQIP support no association between short delays for appendectomy and risk of perforation.
References:
1. 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;60:582-590.e3.
2. Bonadio WA, Brazg J, Telt N, et al: Impact of in-hospital timing to appendectomy on perforation rates in children with appendicitis. J Emerg Med. 2015;49:597–604.
3. Meltzer J, Kunkov S, Chao J, et al. Association of delay in appendectomy with perforation in children with appendicitis. Pediatr Emerg Care. Epub ahead of print 30 September 2016.
4. Kharbanda AB, Macias CG, Stevenson MD, et al. Interrater reliability of clinical findings in children with possible appendicitis. Pediatrics. 2012;129:695-700.
5. Serres SK, Cameron DB, Glass CC, et al. Time to appendectomy and risk of complicated appendicitis and adverse outcomes in children. JAMA Pediatr. 2017; Epub ahead of print 19 June 2017.
Commentary: "Time From Emergency Department Evaluation to Operation and Appendiceal Perforation."
Dear Editor:
I read with interest the recently published study [Pediatrics June 2017, 139 (6) e20160742; DOI: 10.1542/ peds.2016-0742] analyzing the impact of in-hospital duration of time to appendectomy on risk for developing appendiceal perforation in children who present with uncomplicated appendicitis. The authors report that relatively shorter in-hospital delay was not associated with a significantly increased risk for developing perforation.
Below are some concerns regarding the analysis and conclusions:
1. The study objective is to analyze the rate of developing appendiceal perforation as a function of in-hospital time from ED presentation to OR appendectomy in children who present with uncomplicated appendicitis. A prerequisite to accurately assigning pre-operative diagnosis of appendicitis and determining perforation status to answer this study question is ED performance of advanced imaging [either abdominal CT or MRI]. In all, 255 of 955 patients did not receive any pre-operative imaging - and therefore their ED perforation status was indeterminate. The 69 patients with laparoscopic evidence of perforation who did not receive imaging should have been excluded from analysis, since it cannot be determined if perforation was present on admission vs developed during in-hospital time interval awaiting surgery [the main crux of the study]. Also, it appears from Table 1 that, of the remaining 700 patients, 225 had abdominal US as sole diagnostic imaging; I would argue from extensive experience that this modality is [by comparison with abdominal CT] not only inferior for diagnosing appendicitis(1); but, more importantly, highly inaccurate in distinguishing appendiceal perforation status. So likewise, any of the 178 patients with laparoscopic evidence of perforation who had uncomplicated appendicitis diagnosed by abdominal US should've been eliminated from the analysis.
2. Another crucial analytic component is accurate pre-operative assignment of perforation status. The methodology suggests a two part inclusion process: the diagnosis of appendicitis was determined by pathology report; and the diagnosis of perforation was confirmed by surgeon report. It is unclear if all surgical reports were reviewed in each case; or only after perforation was documented per pathology report. If the pathology report was used to screen for perforation, a considerable number of cases could have been misclassified; as it is well documented that pathologist histologic examination to distinguish appendiceal perforation status is associated with a significant false-negative rate [up to 45%] when compared with surgeon visualized diagnosis.(2)
3. There are no radiologic criteria given to objectively determine appendicitis diagnosis and perforation status for those who received either abdominal US or CT.
4. There is no mention of whether all patients studied received ED administered broad spectrum antibiotic therapy. A discrepancy in this variable between groups could have confounded the analysis.
Finally, the authors state in the Discussion that “duration of symptoms has been well accepted as a significant predictor for appendiceal perforation”. By contrast, it is important to regard two large, recently published studies(3,4) of children presenting to the ED with CT-confirmed uncomplicated appendicitis; each showed a direct and linear increase in odds of developing perforation with increasing in-hospital time to appendectomy. Both performed regression analysis, and neither found duration of symptoms was significantly associated with risk for developing perforation.
References:
1. Doria A, Moineddin R, Kellenberger C, et al: US or CT for diagnosis of appendicitis in children and adults? A meta-analysis. Radiology. 2006;241:83-94
2. Bonadio WA: Accurate classification of perforation outcome with pediatric appendicitis. Letter to the Editor. Pediatr Emerg Care 2017;33:March p e3
3. Meltzer J, Kunkov S, Chao J, et al. Association of delay in appendectomy with perforation in children with appendicitis. Pediatr Emerg Care. Epub ahead of print 30 September 2016
4. Bonadio WA, Brazg J, Telt N, et al: Impact of in-hospital timing to appendectomy on perforation rates in children with appendicitis. J Emerg Med 2015;49:597–604