Introduction
Acute appendicitis is the most common acute surgical condition in children. The lifetime risk of appendicitis is 8.6% for males and 6.7% for females (1). While male predominance is well-documented in appendicitis, it remains underexplored in terms of potential sex-related disparities in presentation, emergency management, and clinical outcomes, specifically in pediatric emergency care.
Studies have suggested that female patients may be at a higher risk for delayed diagnosis and increased rates of negative appendectomy (2-4). Teixeira et al. (5) identified female sex as an independent predictor of perforation in patients of all ages with appendicitis. In pediatric patients, Salö et al. (6) found that females had higher rates of gangrenous appendicitis and operative complications, concluding that these findings and the reasons behind them needed further studies.
We aimed to investigate the sex-based differences in the emergency presentation and perioperative outcomes of children diagnosed with complicated appendicitis, focusing on potential delays in presentation to the emergency department (ED), early clinical assessment, and postoperative morbidity.
Methods
This retrospective study was conducted on pediatric patients under 18 years who presented to the ED and were diagnosed with complicated appendicitis requiring laparoscopic appendectomy from January 2012 through December 2022 at the Schneider Children’s Medical Center of Israel, Petah Tikva, Israel. Patients were identified using diagnostic codes per the International Classification of Diseases, 9th Revision for appendicitis. Complicated appendicitis was defined as intraoperatively confirmed gangrenous or perforated appendicitis with or without peritonitis, and laparoscopic appendectomy as using trocars through the umbilicus, left lower abdomen, or suprapubic region, as per the standard practice. The study protocol was approved by the institutional review board of our hospital with a waiver for informed consent (IRB no. RMC-0560-18).
Upon the ED arrival, all pediatric patients who presented with right lower quadrant abdominal pain, accompanied by symptoms such as fever, vomiting, or diarrhea, underwent standardized evaluations. This included physical examinations, laboratory tests, such as white blood cell count, C-reactive protein, or electrolytes, and preoperative abdominal ultrasonography (US) or computed tomography.
All the patients who were diagnosed with acute appendicitis received empirical intravenous antibiotics, such as ceftriaxone plus metronidazole. In the case of intraoperatively confirmed appendiceal perforation, the intraperitoneal fluid was aspirated for culture and if necessary, drained. For the patients diagnosed with complicated appendicitis, follow-up blood tests were routinely obtained on postoperative day 3. In cases of persistent leukocytosis or documented fever, a postoperative US was performed on the same or following day. If the US demonstrated intra-abdominal fluid, antibiotic therapy was escalated to piperacillin-tazobactam.
We collected data from the patients’ medical records, in terms of their age, sex, duration of symptoms, clinical presentation (fever, vomiting, or diarrhea), values of preoperative white blood cell count and C-reactive protein concentration, fecalith on computed tomography or US, intraoperative findings, and postoperative outcomes. The intraoperative findings included the presence of gangrenous or perforated appendicitis, periappendiceal abscess, or peritonitis. The postoperative outcomes included the use of piperacillin-tazobactam, resistant bacteria in the abdominal fluids, hospital length of stay, and rehospitalization.
Shapiro-Wilk tests were performed for continuous variables to determine whether they are normally distributed. Accordingly, continuous variables were compared using independent sample t-tests or Mann-Whitney tests, for normally distributed and non-normally distributed variables, respectively. Pearson chi-square tests of independence or Fisher exact tests were performed for categorical variables, as needed. Statistical significance was defined as a 2-tailed P < 0.05. All analyses were performed using Python (Python Software Foundation, https://www.python.org).
Results
1. Patients’ characteristics
Out of 300 patients with complicated appendicitis, 123 were female (41.0%). Patients’ characteristics are summarized in Table 1. None of the laparoscopic operations required a conversion to laparotomy. Notably, there were no cases of surgical site infection as defined by a superficial or deep incisional surgical site infection. There were no sex-based differences in the intraoperative findings. We noted that the female patients showed more frequent use of piperacillin-tazobactam (males, 14.7% vs. females, 25.2%; P = 0.020) and a longer median hospital length of stay (6.0 days [interquartile range, 5.0-8.0] vs. 7.5 days [5.0-10.0]; P = 0.048).
2. Sub-analysis of patients who received piperacillin-tazobactam
A sub-analysis was conducted on patients who required antibiotic regimen escalations to piperacillin-tazobactam during the first hospital stay. As a result, the females showed a longer median duration of symptoms before hospitalization (males, 2.0 days [interquartile range, 1.0-3.0] vs. females, 3.0 days [2.0-4.5]; P = 0.031), and a higher frequency of intra-abdominal fluids on the postoperative US (23.1% vs. 32.3%; P = 0.049; Table 2). No difference was observed in the rates of resistant bacteria in the abdominal fluids between the sexes.
Discussion
This study highlights important sex-related disparities in pediatric emergency care for complicated appendicitis. Despite similar clinical presentations and laboratory findings at the time of ED evaluation, we found that compared to the male patients, females with complicated appendicitis might have a slower recovery with persistent manifestations, as shown by the longer hospital length of stay and more frequent use of broad-spectrum antibiotics (Table 1). These findings suggest a more advanced disease in the female patients at ED presentation, raising the question of whether the observed disparities stem from biological differences in disease progression or a delay in seeking medical care among girls. The female patients’ slower recovery was also represented by the longer duration of symptoms in the sub-analysis (Table 2).
The findings align with previous research showing sex disparities in emergency medical decision-making. Similar trends have been observed in adult cardiovascular emergencies (7), where women experience longer delays in seeking care and higher rates of complications. The reasons for this disparity are multifaceted, encompassing societal norms, differences in symptom perception, varying levels of health literacy, and economic factors. The disparity highlights a concerning pattern where women may be underutilizing crucial hospital-based services, potentially leading to delayed diagnoses and poorer health outcomes in acute medical situations (8-10). However, to the best of our knowledge, this is one of the first studies to document similar trends in complicated appendicitis in pediatric emergency settings.
This study has an inherent limitation in its single tertiary center and retrospective design, possibly limiting the generalizability of the findings. Differences in healthcare access, referral patterns, and institutional management protocols across various settings could influence the observed sex disparities. However, this is one of the few studies that specifically investigated sex disparities in pediatric emergency surgical care, providing insight into the understudied area. In addition, by focusing on a well-defined and homogeneous cohort of patients with complicated appendicitis and analyzing standardized perioperative data, we tried to minimize potential confounders related to disease severity at ED presentation.
In conclusion, female pediatric patients with complicated appendicitis may experience a more serious postoperative morbidity. These findings underscore the need for increased awareness among caregivers and primary care providers regarding the potential for delayed presentation of appendicitis in females, in order to recognize and prioritize early evaluation of abdominal pain in female patients. Timely ED presentation may help reduce postoperative complications and improve outcomes.
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