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Reevaluating Nonoperative Management for Pediatric Uncomplicated Acute Appendicitis A Systematic Review and Meta-Analysis

Author/s: 
Isabella Faria, Ana Carolina Godinho Cintra, Luiz Gustavo Albuquerque Mello de Oliveira

Importance: Nonoperative management (NOM) has emerged as a potential alternative to surgery for acute uncomplicated appendicitis in children; however, while short-term outcomes are often favorable, concerns remain about treatment durability, complication rates, and long-term failure. An updated meta-analysis of randomized clinical trials (RCTs) may help clarify the comparative safety and effectiveness of NOM vs appendectomy.

Objective: To evaluate the safety and effectiveness of NOM compared with appendectomy for uncomplicated appendicitis in children using the highest level of available evidence.

Data sources: A systematic review of PubMed, Embase, Scopus, Cochrane, and Web of Science was conducted from inception through March 2025 to identify randomized clinical trials comparing NOM with surgical management in pediatric patients.

Study selection: RCTs comparing NOM vs surgical management in pediatric patients younger than 18 years were included. Nonrandomized and quasi-randomized studies were excluded.

Data extraction and synthesis: Data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses were conducted using random-effects models. Risk of bias was assessed independently by multiple reviewers. Trial sequential analysis was performed to determine whether the evidence was sufficiently robust and conclusive.

Main outcomes and measures: The primary outcomes were treatment failure and treatment success in 1 year and major complications (Clavien-Dindo grade ≥IIIb). Secondary outcomes included time to return to school and time to return to normal activity.

Results: Of 1246 studies screened, 7 RCTs, including 1480 pediatric patients, met inclusion criteria. Treatment failure was significantly higher in the NOM group than in the appendectomy group at 1 year (risk ratio [RR], 4.97; 95% CI, 3.57-6.91; I2 = 0.0%). Treatment success was significantly lower in the NOM group at 1 year (RR, 0.67; 95% CI, 0.60-0.75; I2 = 31.1%). Major complications classified as Clavien-Dindo grade IIIb or worse were more frequent in the NOM group (RR, 33.37; 95% CI, 7.89-141.05; I2 = 9.5%). Appendicitis recurred at a rate of 18.47 events/100 observations (95% CI, 12.62-25.07 events/100 observations; I2 = 48.5%) among patients who received NOM. NOM, compared with appendectomy, was associated with a modestly faster return to school (mean difference, -1.36 days; 95% CI, -2.64 to -0.08 days; P = .04; I2 = 57.7%) and return to normal activities (-4.93 days; 95% CI, -8.68 to -1.19 days; P = .01; I2 = 87.2%), although this may be offset by subsequent readmissions or reintervention. Trial sequential analysis demonstrated the robustness and conclusiveness of primary outcomes.

Conclusions and relevance: In contrast to earlier studies, this meta-analysis found significantly higher treatment failure and major complication rates within a year with NOM among children and adolescents. The meta-analysis provides pediatricians and pediatric surgeons with up-to-date data to inform shared decision-making with families and encourage individualized, patient-centered treatment.

Keywords 
Humans Appendicitis Appendectomy Patient Readmission

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis

Author/s: 
CODA Collaborative, Flum, David R., Davidson, Giana H., Monsell, Sarah E., Shapiro, Nathan I., Odom, Stephen R., Sanchez, Sabrina E., Drake, F.T., Fischkoff, Katherine, Johnson, Jeffrey, Patton, Joe H., Evans, Heather, Cuschieri, Joseph, Sabbatini, Amber K., Faine, Brett A., Skeete, Dionne A., Liang, Mike K., Sohn, Vance, McGrane, Karen", Matthew E., Chung, Bruce, Carter, Damien W., Ayoung-Chee, Patricia, Chiang, William, Rushing, Amy, Steinberg, Steven, Foster, Careen S., Schaetzel, Shaina M., Price, Thea P., Mandell, Kathrine A., Ferrigno, Lisa, Salzberg, Matthew, DeUgarte, Daniel A., Kaji, Amy H., Moran, Gregory J., Saltzman, Darin, Alam, Hasan B., Park, Pauline K., Kao, Lilian S., Thompson, Callie M., Self, Wesley H., Yu, Julianna T., Wiebusch, Abigail, Winchell, Robert J., Clark, Sunday, Krishnadasan, Anusha, Fannon, Erin, Lavallee, Danielle C., Comstock, Bryan A., Bizzell, Bonnie, Heagerty, Patrick J., Kessler, Larry G., Talan, David A.

BACKGROUND

Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis.

METHODS

We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life–5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith.

RESULTS

In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], −0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50).

CONCLUSIONS

For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith.

Keywords 
antibiotics Appendicitis Appendectomy Antibiotic Therapy
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