SGEM#476: Cuts like a Knife or Antibiotics for Pediatric Appendicitis

Reference:  St Peter, et al. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomized noni-inferiority trial. The Lancet. Jan 2025 Date: March 19, 2025 Dr. Camille Wu Guest Skeptic: Dr. Camille Wu is a paediatric surgeon based at Sydney Children’s Hospital where she is the Head of Department. She is also on the Training Committee of Paediatric Surgery for Australia and New Zealand. Case: A 10-year-old boy presents to the emergency department (ED) with his parents. He started having abdominal pain yesterday and did not want to eat. Today, his abdominal pain worsened, and he developed a fever. On examination, he looks uncomfortable and is tender to palpation in the right lower quadrant. You tell the parents that his examination is concerning for appendicitis. You order an ultrasound that demonstrates a dilated and non-compressible appendix. You consult the surgery team and both of you come to speak with the family. His parents tell you, “His sister was diagnosed with appendicitis during the Covid pandemic. At that time, she was admitted to the hospital but just treated with antibiotics. She was able to go home and has done well since that time. Do you think he needs surgery, or can he be treated with antibiotics as well?” Background: Acute appendicitis is one of the most common pediatric surgical complaints that we encounter in the ED. Traditionally, appendicectomy has been the gold standard for treatment, based on its effectiveness in preventing complications such as perforation, abscess formation, and peritonitis​. This is typically done laparoscopically through a few small incisions. The concept of non-operative treatment of appendicitis (NOTA) with antibiotics has gained interest over the past decade. This has been supported by growing evidence suggesting that some cases of uncomplicated appendicitis may resolve without surgery​. We have covered NOTA before on the SGEM that included some meta-analyses, randomized controlled trials, and observational studies. SGEM #115: Complicated-Non-operative Treatment of Appendicitis (NOTA) SGEM #180: The First Cut is the Deepest- N.O.T. for Paediatric Appendicitis SGEM #256: Doctor Doctor Give Me the News, I Gotta Bad Case of RLQ Pain- Should I have an Appendectomy? SGEM #345: Checking In, Checking Out for Non-Operative Treatment of Appendicitis (APPAC II RCT) SGEM #384: Take Me Out Tonight, I Don’t Want to Perforate My Appendix Alright The results have been mixed. Some of these studies have suggested that antibiotic therapy is non-inferior to surgical management while other studies have suggested antibiotic therapy did not meet criteria for non-inferiority compared to appendectomy. Most of these studies were conducted in the adult population with fewer studies conducted in children. The question remains: To cut or not to cut? Clinical Question: In children with acute uncomplicated appendicitis, is treatment with antibiotics non-inferior to appendicectomy? Reference:  St Peter, et al. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomized noni-inferiority trial. The Lancet. Jan 2025 Population: Children aged 5-16 years with suspected non-perforated appendicitis based on clinical diagnosis +/- imaging Excluded: suspicion of perforated appendicitis, appendix mass/phlegmon, previous antibiotic treatment, positive pregnancy test, current treatment for malignancy, comorbid condition altering length of stay Intervention: Antibiotic therapy, initially with IV antibiotics followed by oral antibiotics after clinical improvement Comparison: Laparoscopic appendectomy Outcome: Primary Outcome: Treatment failure within 1 year. Secondary: Complications (adverse events that required interventions without general anesthesia), length of hospital stay, patient-reported outcomes (quality of life and pain scores) and healthcare utilization. Trial: Pragmatic, multicentre, parallel-group, unmasked, randomized, non-inferiority trial Authors’ Conclusions: Based on cumulative failure rates and a 20% non-inferiority margin, antibiotic management of non-perforated appendicitis was inferior to appendicectomy. Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Unsure  The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Unsure The patients in both groups were similar with respect to prognostic factors. Yes. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No. All groups were treated equally except for the intervention. Unsure Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure Financial conflicts of interest. None Results: They recruited 936 patients from 11 children’s hospitals in Canada, the US, Finland, Sweden, and Singapore. 459 were assigned to the appendicectomy group and 477 were assigned to the antibiotic group. Key Result: Antibiotic therapy was inferior to appendicectomy for management of non-perforated appendicitis. Primary Outcome: 34% of the patients in the antibiotic group had treatment failure compared to 7% of the appendicectomy group. That was a difference of 26.7% (90%CI 22.4-30.9). Most treatment failure in the appendicectomy group was due to negative pathology. In the antibiotic group, 72 (47%) met definition of treatment failure during the first admission. Secondary Outcomes:  Neither of the groups had deaths or serious adverse events. The relative risk of having an adverse event related to the antibiotic treatment compared to the appendicectomy was 4.3 (95% CI 2.1-8.7). Most of these adverse events were classified as Gastrointestinal Distress. Median length of stay was 1.0 day (IQR 0.76-1.68) for the appendicectomy group compared to 1.25 days (IQR 0.92-2.09) for the antibiotic group. The patients from the antibiotic group spent more time in the hospital during the 12 month follow up period 1.6 days (IQR 1.0-2.6) compared to 1.0 days (IQR 0.75-1.7). The antibiotic group was able to return to normal activity and school faster than the appendicectomy group. They also did not require pain medications compared to the appendectomy Approximately three-quarters (73%) of the families surveyed from both groups reported being satisfied with their treatment. Diagnosis of Appendicitis In previous studies, the way a diagnosis of appendicitis is made has varied. Some studies have included imaging findings on CT scan or ultrasound. Some studies have included lab tests. This study included patients with a diagnosis of simple, non-perforated appendicitis. They excluded those with suspicion of perforated appendicitis. How was this diagnosis made? We went back to the trial protocol on ClinicalTrials.gov to find some more details. It appears that all children with suspected acute non-perforated appendicitis were assessed by the on-call surgeon. The diagnosis could be made based on clinical suspicion with or without ultrasound imaging. What is the gold standard for diagnosing appendicitis? We would imagine that surgical pathology consistent with the diagnosis is best but also recognize that is does not make any sense to remove the appendix of every child in the study. Camille does not rely on imaging. However, often by the time she's called to see the patient in ED, they’ve already had an ultrasound. Sometimes it’s helpful, sometimes it’s unnecessary, and sometimes it’s distracting. One of the common annoying scenarios is the finding of a mildly thickened 7mm appendix in a child who does have right inferior quadrant tenderness with no other signs of appendicitis, and parents are expecting an operation as the ultrasound says “appendicitis’ and the referring hospital has told them that’s why they were getting transferred. Many of these kids have a viral illness, causing lymphoid tissue in the wall of the appendix to hypertrophy, thereby enlarging the appendix. Treat the patient, not the test or image finding. Tests are an adjunct to clinical evaluation. They help us to confirm our diagnosis. How sure does a surgeon need to be to take a patient to theatre? How sure does an ED doctor need to be to call their surgeon to review? Seems like the threshold is different for different specialties, different hospitals, different practitioners, and different countries! Selection Bias Of the patients screened for eligibility in the study, 90% were excluded. Of those excluded, ~40% were excluded due to perforated appendicitis or suspected perforation, and the other 60% were excluded because they either declined to participate or “other reasons.” Suspected perforation seems fairly subjective. I asked Camille to comment on how she clinically distinguishes between perforated or non-perforated appendicitis and the accuracy of making that determination based solely on physical exam. Duration of symptoms: the authors also included duration ≥ or < 48 hours in their randomisation. Surgical teaching is that perforation occurs around Day 3, so be more suspicious of this group. Beware the kids under 5, they tend to perforate earlier at Day 2. Also be suspicious of pain on day 3 that’s suddenly better, but the patient is sicker. Young and atypical presentation: presents like gastroenteritis, rather than the classic “central pain migrating to right inferior quadrant.