Pre-hospital time and risk of perforation in patients with acute appendicitis in 112 countries (AlliGatOr): an international, prospective, observational cohort study

Abstract

Background. Acute appendicitis is the most common surgical emergency worldwide. Concern that delayed treatment might increase perforation can lead to unnecessary surgery and high rates of negative appendicectomy, where a normal, non-inflamed appendix is removed. However, whether perforation is related to pre-hospital time (symptom onset to first surgical assessment) has not been explored in contemporary global data. Methods. We conducted an international, multicentre, prospective, observational cohort study (AlliGatOr) of patients undergoing emergency appendicectomy for suspected acute appendicitis in 1377 hospitals across 112 countries. We included all consecutive eligible patients and excluded patients undergoing appendicectomy for indications other than suspected acute appendicitis. Each participating hospital entered data from medical records prospectively into the Research Electronic Data Capture platform. The primary outcome was perforation and the primary exposure was pre-hospital time (categorised as <12 h, 12–23 h, 24–47 h, 48–71 h, and ≥72 h). Follow-up was for 30 days after surgery to assess postoperative outcomes. In-hospital time (first surgical assessment to skin incision) was a key secondary exposure. We estimated adjusted risk ratios (aRRs) using multilevel Poisson regression. Multivariable analyses used complete cases; missing data were not imputed. The study is registered with ClinicalTrials.gov (NCT06774001) and is completed. Findings. Between Feb 3 and May 25, 2025, we enrolled 45 218 patients with a median age of 27 years (IQR 18–41); 25 218 (55⋅8%) were male and 19 996 (44⋅2%) were female. 42 317 patients were included in the primary analysis, of whom 13 560 (32⋅0%) had perforation. The adjusted primary model included 41 740 patients with complete covariate data. Access to CT imaging varied across income groups: 12 232 (58⋅6%) of 20 861 patients in high-income countries, 4597 (37⋅1%) of 12 388 in upper-middle-income countries, 1769 (19⋅2%) of 9192 in lower-middle-income countries, and 156 (5⋅6%) of 2769 in low-income countries. Minimally invasive surgery was used in 19 985 (95⋅8%) of 20 861 patients, 6817 (55⋅0%) of 12 390, 2613 (28⋅4%) of 9195, and 203 (7⋅3%) of 2770, respectively. Perforation increased with pre-hospital times, from 2629 (22⋅9%) of 11 487 patients at less than 12 h (reference) to 2671 (25⋅8%) of 10 371 at 12–23 h (aRR 1⋅07 [95% CI 1⋅01–1⋅13]; p=0⋅021), 2969 (33⋅6%) of 8826 at 24–47 h (1⋅36 [1⋅28–1⋅44]; p<0⋅0001), 1933 (41⋅7%) of 4640 at 48–71 h (1⋅62 [1⋅52–1⋅72]; p<0⋅0001), and 3350 (48⋅0%) of 6974 at pre-hospital times of at least 72 h (1⋅85 [1⋅75–1⋅95]; p<0⋅0001). Longer in-hospital time was associated with lower perforation risk: versus less than 12 h, aRRs were 0⋅95 (95% CI 0⋅91–1⋅00; p=0⋅034) for 12–23 h, 0⋅87 (0⋅82–0⋅93; p<0⋅0001) for 24–47 h, and 0⋅82 (0⋅75–0⋅90; p<0⋅0001) for at least 48 h. Perforation was associated with higher complication risk at 30 days (2⋅36 [2⋅24–2⋅48]; p<0⋅0001). Complications were also higher after open surgery than for minimally invasive surgery (1⋅30 [1⋅20–1⋅41]; p<0⋅0001). Negative appendicectomy occurred in 2365 (5⋅2%) of 45 218 patients and was lower among those who had preoperative CT than among those who did not (0⋅69 [0⋅62–0⋅77]; p<0⋅0001). Interpretation. These findings support prioritising surgical assessment within 24 h as a target to reduce the burden of perforated appendicitis. Preoperative CT imaging was associated with lower rates of unnecessary operations; access to CT and minimally invasive surgery varied markedly by country income group.