Early Appendectomy Shortens Antibiotic Course and Hospital Stay in Children with Early Perforated Appendicitis Accepted Manuscript Early Appendectomy Shortens Antibiotic Course and Hospital Stay in Ch[.]
Accepted Manuscript Early Appendectomy Shortens Antibiotic Course and Hospital Stay in Children with Early Perforated Appendicitis Hsin-Yu Tsai, MD, Hsun-Chin Chao, MD, Wan-Ju Yu, MD PII: S1875-9572(17)30051-7 DOI: 10.1016/j.pedneo.2016.09.001 Reference: PEDN 638 To appear in: Pediatrics & Neonatology Received Date: 23 June 2016 Revised Date: 10 August 2016 Accepted Date: 20 September 2016 Please cite this article as: Tsai H-Y, Chao H-C, Yu W-J, Early Appendectomy Shortens Antibiotic Course and Hospital Stay in Children with Early Perforated Appendicitis, Pediatrics and Neonatology (2017), doi: 10.1016/j.pedneo.2016.09.001 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain ACCEPTED MANUSCRIPT Abstract Background: The optimal management of perforated appendicitis in the pediatric population RI PT has been controversial This study aimed to compare the therapeutic efficacy between conservative treatment (CS) and early appendectomy (EA) in pediatric perforated appendicitis, and to determine whether surgical intervention is an optimal treatment modality for early SC perforated appendicitis in children M AN U Methods: Patients treated between January 2012 and April 2014, aged 0-18 years with an imaging-based diagnosis of perforated appendicitis were retrospectively reviewed Patients were classified into non-abscess and abscess groups by image findings, and were further TE D categorized into CS and EA groups by treatment modality Early perforated appendicitis was defined as having duration of symptoms (DOS) ≤ days, C-reactive protein (CRP) level ≤ EP 200mg/L, maximum abscess diameter ≤ cm, and absence of general peritonitis and unstable vital signs The clinical features and therapeutic outcomes were compared between CS and AC C EA in each group Results: A total of 326 patients had confirmed appendicitis, including 116 patients with image diagnosis of perforation The CS group had significantly longer DOS, larger abscess and higher serum CRP levels at presentation (all p < 0.05) Patients in the EA group had shorter antibiotic course and length of hospitalization (LOH), and a lower rate of antibiotic escalation ACCEPTED MANUSCRIPT than those in CS group (p values < 0.001, < 0.001, and < 0.05 respectively) In patients with early perforated appendicitis, the CS and EA groups showed no difference in baseline disease severity Patients in the EA group also had a shorter antibiotic course and length of RI PT hospitalization (LOH) than those in the CS group (p values < 0.001, and < 0.001 respectively) SC Conclusion: Compared to conservative treatment, early appendectomy shortens the antibiotic M AN U course and hospital stay in pediatric early perforated appendicitis, even in the presence of small abscesses Key Words: perforated appendicitis; conservative treatment; appendectomy; children; length AC C EP TE D of stay ACCEPTED MANUSCRIPT Introduction Acute appendicitis is one of the most common surgical abdominal diseases in the pediatric RI PT population Appendicitis accounts for 1%-8% of the diagnosis in children visiting the emergency department for acute abdominal pain.1,2 The perforation rate is high (up to 51%) in pediatric appendicitis, especially in younger children.3 The image diagnosis of perforated SC appendicitis could be accurately attained with abdominal ultrasonography or computed M AN U tomography.4,5 Perforated appendicitis may result in complications leading to high medical expenses Treatment for this condition is still controversial, and there is no consensus in the TE D management of pediatric perforated appendicitis Traditionally, conservative treatment (CS) with interval appendectomy is preferred over early appendectomy (EA) in reducing EP postoperative complications.6–10 However, recent opinions support the role of EA in AC C non-abscess patients.11,12 The current study presented a two-year experience (2012-2014) of pediatric perforated appendicitis in a tertiary center in Taiwan The aim of this study is to compare the therapeutic efficacy between CS and EA in children with early perforated appendicitis The demographic information, laboratory values, therapeutic efficacy, complications, hospital duration, and readmission rate were statistically analyzed ACCEPTED MANUSCRIPT Methods Study design RI PT Between January 2012 and April 2014, patients from 0-18 years old, treated at Chang Gung Children’s Medical Center with a diagnosis of acute appendicitis, were reviewed Only those patients with acute appendicitis confirmed through SC retrospectively ultrasonography (US), computed tomography (CT), or histology were included The US was M AN U performed by a group of experienced pediatric gastroenterologists, and CT was interpreted by experienced radiologists Presence of abscess, phlegmon, free ascites distant from the appendix, extraluminal air or appendicolith, or appendiceal wall defect defines suspicious TE D perforation Patients having uncertain diagnosis, incomplete data, underlying systemic illness, or secondary appendicitis were excluded Those with suspicious perforated appendicitis on EP US and/or CT were enrolled for analysis AC C In our institution, the pediatrician routinely consulted the pediatric surgeon regarding the option of surgical intervention in those patients with clinical presentations and imaging findings consistent with appendicitis Considering our government’s case payment regulation for pediatric patients receiving operation for acute appendicitis, the pediatric surgeon performed the operation in cases of non-perforated, generalized peritonitis, or advanced appendicitis with clinically ill-appearing or critical complications (intractable abdominal pain, ACCEPTED MANUSCRIPT unstable vital signs, bowel obstruction), or cases with mark elevation of serum C-reactive protein (CRP) (> 200 mg/L) There was no consensus of performing surgical intervention in those patients with early perforated appendicitis Those patients with initial successful RI PT non-operative treatment were assigned follow-up at outpatient department for the subsequent interval appendectomy SC Children with suspected perforated appendicitis were divided into two groups - abscess M AN U (ABS) and non-abscess (NA) groups - according to the presence or absence of appendiceal abscess or phlegmon Patients in each group were further classified based on two treatment modalities: CS (ABS-CS and NA-CS) and EA (ABS-EA and NA-EA) Patients who received TE D antibiotic treatment, with or without CT-guided drainage, were classified as CS EA was defined as appendectomy performed within 24 hours after acute appendicitis was diagnosed EP Laparoscopic appendectomy was the standard operative method in our institution Those patients with persistent high-spiking fever, or advanced conditions with critical complications AC C (intractable abdominal pain, unstable hemodynamics, bowel obstruction) underwent operation beyond 24 hours of admission were excluded from the study Data collection Data collected from the medical records included demographic information, duration of symptoms (DOS) before hospitalization, laboratory values (peripheral white blood cell (WBC) ACCEPTED MANUSCRIPT counts, neutrophil counts, band-cell ratio, and serum CRP level), image findings, use of parenteral nutrition, timing of appendectomy, operative results, the categories of initial intravenous (IV) antibiotics, need of escalation, duration of IV and total (IV plus per-oral) RI PT antibiotic treatment, length of hospitalization (LOH), and early readmission (within one month after discharge from the hospital) The etiologies of early readmission included SC adhesion ileus, residual abscess, recurrent appendicitis, and wound complications M AN U Protocol of Antibiotic treatment In our institution, the routine first-line IV antibiotics for acute appendicitis were ampicillin or a first-generation cephalosporin, plus gentamicin and metronidazole Second-line parenteral regimens contained a third-generation cephalosporin Imipenem or TE D antibiotic piperacillin-tazobactam was used for advanced conditions In EA group, the use of EP postoperative antibiotic was determined by intraoperative findings and postoperative complications Antibiotic escalation would be considered in patients who have no AC C improvement of clinical symptoms (peritoneal sign, abdominal pain, fever, or vomiting) or laboratory parameters (WBC count, band-cell ratio, or CRP level) in days of initial antibiotic treatment After discharge, amoxicillin-clavulanate was the routinely prescribed oral antibiotics Definition of the early perforation group and subgrouping by serum CRP level ACCEPTED MANUSCRIPT This group was defined as patients having DOS ≤ days, serum CRP level ≤ 200mg/L, and size of abscess or phlegmon ≤ 5cm Those patients with generalized peritonitis or severe systemic manifestations (cardiopulmonary dysfunction, renal failure, septic shock, etc.) were RI PT excluded in this group Serum CRP cutoff level was determined based on the observation that all severe complications occurred in patients with a CRP level > 200mg/L; besides, only a SC small proportion of patient with a CRP level >200mg/L received EA In our institution, M AN U patients with abscesses > cm were routinely evaluated for computed tomography-guided drainage by radiologists; thus these patients were excluded from the early perforation group For further analysis, patients in early perforation group were further divided into Group (CRP ≤ 100 mg/L) and Group (100 mg/L < CRP ≤ 200 mg/L) Children in each subgroup EP Statistical analysis TE D with abscess formation were evaluated separately Statistical analysis was performed with IBM SPSS Statistics version 22 Continuous variables AC C were analyzed with the Student’s t test Categorical data were analyzed with a Chi-square test or Fisher’s exact test A p-value of < 0.05 was considered to be significant All tests were two-tailed Ethical considerations The study was approved at our institution by the ethics committee of Chang Gung ACCEPTED MANUSCRIPT Memorial Hospital with a waiver of informed consent (CGMH 103-1842B) However, all AC C EP TE D M AN U SC RI PT patient records/information was anonymized and de-identified prior to analysis ACCEPTED MANUSCRIPT Results Patient inclusion and grouping RI PT During the 2-year study period, a total of 455 children were diagnosed with acute appendicitis 129 patients not fulfilling the inclusion criteria were excluded Of the remaining 326 patients SC having either imaging or histological confirmation of acute appendicitis, 122 patients were identified as having perforated appendicitis, using image diagnosis: 45 (36.9%) had M AN U abdominal US alone, 37 (30.3%) had only CT and 40 (32.8%) patients had both US and CT examinations 81 (66.4%) patients were identified as having appendiceal abscess or phlegmon (ABS group), and 41 (33.6%) were not (NA group) TE D A total of 80 children received conservative management: 64 in the ABS group (ABS-CS) and 16 in the NA group (NA-CS) EA was performed in 17 patients in ABS group (ABS-EA) EP and 25 patients in NA group (NA-EA); most of these patients received laparoscopic The mean AC C appendectomy, except one patient in ABS-EA group and two in NA-EA group latency from admission to operating room was 10.3 hours Intractable abdominal pain (36/42) and bilious vomiting suggesting bowel obstruction (13/42) were two indications for EA Four patients in NA-EA and two in ABS-EA groups were found to have non-perforated appendix intra-operatively, and were therefore excluded from the analysis (Figure 1) Of the four patients with non-perforated appendix in NA-EA group, all did not have gross appendiceal ACCEPTED MANUSCRIPT found that all the major complications, such as septic shock, pneumoperitoneum, requirement of intensive care, and need for parenteral nutrition occurred in those patients with an initial RI PT CRP level > 200 mg/L When categorizing patients fulfilling the criteria of early perforation, there was no statistical difference in baseline disease severity between the conservative and surgical groups SC At least for non-abscess patients with serum CRP levels ≤ 200 mg/L and patients having M AN U localized small abscesses with serum CRP level ≤ 100 mg/L, this study disclosed a promising result favoring EA with respect to shorter LOH, briefer parenteral and total antibiotic course, and possible lower rate of antibiotic escalation For patients presenting with small appendiceal TE D abscess and serum CRP level in the range of 100-200 mg/L, EA may also be beneficial Based on the criteria we developed, up to 54.3% (63/116) children with early perforated appendicitis EP would become potential candidates for EA There are some limitations of this study First of all, this was a retrospective review, with AC C an inherent bias in patient selection Patients undergoing EA had milder disease severity A serum CRP level greater than 100 mg/L often made our surgeons defer EA The observation was especially true in patients with abscess formation Thus, we need more cases in this group to draw a sufficient conclusion Second, CT-guided drainage for appendiceal abscess was rarely performed in our facility Although some literature questions the role of CT-guided drainage,26 the infrequent drainage procedure could adversely affect the efficacy of 18 ACCEPTED MANUSCRIPT conservative treatment in patients with large abscesses Third, resistant organisms are increasingly found in appendiceal abscess culture In some centers, piperacillin-tazobactam is considered an appropriate first-line treatment.27 Our current antibiotic protocol may not be RI PT effective enough in advanced cases, which may cause longer treatment duration and higher antibiotic escalation rate Thus, a complete microbial analysis is required to guide proper SC antibiotic choices M AN U In conclusion, perforated appendicitis is an important acute abdominal disease in the pediatric population, but the optimal therapeutic modality is still controversial Despite some limitations, our study provides a new opinion that patients fulfilling the early perforation TE D criteria may benefit from EA, even in the presence of small abscesses EA could shorten the antibiotic duration and LOH, and lower the possibility of antibiotic escalation in some AC C EP patients Further prospective studies are required to confirm the conclusion 19 ... early appendectomy shortens the antibiotic M AN U course and hospital stay in pediatric early perforated appendicitis, even in the presence of small abscesses Key Words: perforated appendicitis; conservative... findings, and were further TE D categorized into CS and EA groups by treatment modality Early perforated appendicitis was defined as having duration of symptoms (DOS) ≤ days, C-reactive protein... 0.001, and < 0.05 respectively) In patients with early perforated appendicitis, the CS and EA groups showed no difference in baseline disease severity Patients in the EA group also had a shorter antibiotic