ORIGINAL ARTICLE

Introduction

Acute appendicitis (AA) is the most common surgical pathology in cases of acute abdomen across different age groups; 1-2% of hospitalized pediatric patients are admitted for surgical reasons. In general, pediatric patients with abdominal pain represent 1-8% of the population with acute appendicitis. However, acute appendicitis is rare among preschool students. Despite the availability of imaging techniques such as ultrasound and tomography, diagnosing AA in pediatric patients remains challenging, leading to a high proportion of children experiencing late complications such as perforation, which in turn causes obstructions, or the presence of sepsis and peritonitis that prolong hospital stays and are associated with a higher frequency of death <sup>1 ➤
1. Almaramhy HH. Acute appendicitis in young children less than 5 years: review article. Ital J Pediatr. 2017;43:15. doi:10.1186/s13052-017-0335-2</sup> .

The incidence of AA is heterogeneous; for example, in children aged 0-4 years, it is observed in two out of every 10,000. In low- or middle-income countries, the higher frequency of complications is due to limited access to healthcare services, the distance between homes and specialized care centers, or delayed diagnoses caused by poor or absent symptom expression in children, making diagnosis more challenging in younger ages <sup>2 ➤
2. Padrón Arredondo G, Padrón Arredondo G. Apendicitis en niños de 0 a 3 años en un hospital general de segundo nivel. Análisis de cinco años (2013-2017). Cir Gen. 2019;41(3):177–83.</sup> .

In pediatric patients, the high cost generated by complications is evident; however, in recent years, there has been significant progress in perioperative care <sup>3 ➤
3. López SLG, Dalmau LPG, Delgado ZQ, Núñez BRR, Romero BEF, Rodríguez YP. Apendicitis aguda en el niño: guía de práctica clínica. Rev Cuba Pediatría [Internet]. 2020 [citado el 5 de enero de 2022];92(4). Disponible en: http://www.revpediatria.sld.cu/index.php/ped/article/view/1088</sup> .

In a previous study conducted in Peru, it was observed that appendectomy is performed through emergency rooms, with open and laparoscopic surgeries accounting for 51.6% and 48.4%, respectively, in patients aged 2 to 14 years <sup>4 ➤
4. Mesta CP-S, González - Fernández H, Paz-Soldán Oblitas C. Complicaciones quirúrgicas en pacientes pediátricos con apendicitis aguda complicada en cirugías abiertas y laparoscópica en un centro de referencia nacional. Rev Fac Med Humana. 2020;20(4):624–9. doi:10.25176/rfmh.20i4.2951</sup> .

This research is crucial due to the high incidence and severity of complications associated with acute appendicitis, particularly in the pediatric population. In contexts like Peru, where access to healthcare services can be limited and diagnoses are often delayed, identifying these risk factors is essential to improve early intervention strategies and reduce morbidity and mortality rates. Understanding the specific factors contributing to the progression of complicated appendicitis can guide healthcare professionals in implementing more effective protocols and optimizing available resources for the adequate management of these cases. The objective of the present study was to determine the risk factors associated with appendectomy in patients at a pediatric emergency hospital in Peru.

Methods

Study Design:

This is an analytical, observational, retrospective case-control study, as the design allows for the discovery of causal agents related to complicated acute appendicitis.

Study Population:

Individuals under 18 years old who were admitted with complicated acute appendicitis and had surgery, treated at the General Surgery Department of the Pediatric Emergency Hospital during the period 2019-2021 (n=300).

Eligibility Criteria:

Cases were defined as male or female patients under 18 years old, with an operative report, whose diagnosis was complicated acute appendicitis in the necrotic and perforated phase (n=67). Meanwhile, controls consisted of patients with the same characteristics as cases, except for the absence of complicated acute appendicitis (n=67). The power found for the variable leukocytosis was 94.6%.

Variable Definitions:

The dependent variables were complicated acute appendicitis, and the independent variables were age, sex, previous medication, leukocytes (more than 11,000), time taken to visit the emergency room, and the time between the first symptom and the surgery. Covariates included clinical characteristics: abdominal pain, fever, vomiting, nausea, diarrhea, McBurney sign, Blumberg sign.

Procedures:

The researchers collected information from medical records, after authorization from the Ricardo Palma University and the hospital center, and transferred the variables of interest to a spreadsheet.

Statistical Analysis:

Data were collected from the review of medical records and surgical operative reports from the Pediatric Emergency Hospital's Surgery Department during the period 2019-2021. Subsequently, with the obtained data, Microsoft Excel and STATA software were used. For the univariate analysis of qualitative variables, absolute and relative frequencies were calculated; for quantitative variables, the mean and standard deviation were estimated, previously determined according to their normal distribution. For bivariate analysis, contingency tables were used: Chi-square or Fisher's exact test, and for multivariate analysis, logistic regression was used, determining the crude and adjusted odds ratio (OR), as well as 95% confidence intervals.

Ethical Considerations:

This research study has the approval of the Ethics Committee of the Faculty of Human Medicine of Ricardo Palma University (PG-78-021) and the Pediatric Emergency Hospital (letter No. 162-DG-094-2021-OADI-HEP/MINSA). The confidentiality of the information was maintained in accordance with the Peruvian General Health Law, which stipulates that the obtained information must only be used for the purposes of the research.

The pain, folic acid, and transfusional support were managed; additionally, high-flow nasal cannula oxygen therapy was provided. Elective cholecystectomy and vaccination schedule updates were considered, and the patient was prepared for a possible splenectomy. The multidisciplinary management strategy adopted in the emergency, with the collaboration of gastroenterology, hematology, and surgery teams, was crucial in achieving a favorable outcome and avoiding the need for urgent surgical interventions.

RESULTS

A total of 134 pediatric patients were analyzed, of which 67 had complicated acute appendicitis (cases). Regarding age, the mean age of the controls was 10.7 years, while for the cases, it was 13.1 years. The predominant sex in both cases and controls was male. Among the controls, 62.7% received non-analgesic pre-medication, while 50.7% of the controls received analgesics.

Regarding those who presented with leukocytosis, the number of patients with complicated AA was higher compared to the control group (92.5% versus 68.7%, p=0.001). A delay of more than 24 hours in the emergency room was more frequent in the cases (59.7% versus 34.3%, p=0.001), and a time of more than 49 hours from the onset of the first symptom to surgery was observed in patients with complicated AA (38.8% versus 17.9%, p=0.002).

The predominant symptoms in both groups were vomiting, fever, diarrhea, and Blumberg's sign. Vomiting was more common in patients with complicated acute appendicitis than in the control group (85.1% versus 65.7%; p=0.009). The diagnosis of necrotic and perforated appendicitis was 70.1% and 29.9%, respectively (Table 1).

For the simple regression analysis, it was found that patients with leukocytosis had 2.9 times higher odds of having complicated acute appendicitis compared to those with normal leukocytes (OR=2.87; 95% CI: 1.285 – 6.411). Patients with a delay in seeking emergency care of more than 24 hours had 1.8 times higher odds of having complicated acute appendicitis compared to those with a delay of less than 24 hours (OR=1.77; 95% CI: 1.25 – 2.52); those with a time from the onset of symptoms to the surgical procedure of more than 49 hours had 2.7 times higher odds (OR=2.74; 95% CI: 1.39 – 5.39), and those with a time from the onset of symptoms to the surgical procedure of between 24-48 hours had 2.00 times higher odds (OR=2.00; 95% CI: 1.01 – 3.97) of having complicated acute appendicitis compared to those with a time of onset of less than 24 hours. Subsequently, in the multiple regression analysis, the observed association was maintained in terms of direction and magnitude. Pediatric patients with leukocytosis were found to have 2.8 times higher odds of having complicated acute appendicitis compared to those with normal leukocytes (OR=2.79; 95% CI: 1.30 – 6.01). Those with a delay in seeking emergency care of more than 24 hours had 1.7 times higher odds of having complicated acute appendicitis compared to those with a delay of less than 24 hours (OR=1.72; 95% CI: 1.21 – 2.45); those with a time from the onset of symptoms to the surgical procedure of more than 49 hours had three times higher odds (OR=3.01; 95% CI: 1.54 – 5.93), and those with a time from the onset of symptoms to the surgical procedure of between 24-48 hours had 2.3 times higher odds (OR=2.25; 95% CI: 1.14 – 4.44) of having complicated acute appendicitis compared to those with a time of onset of less than 24 hours. Variables such as age, sex, medication, diagnosis of necrotizing and perforated appendicitis, and associated symptoms like nausea, fever, diarrhea, McBurney's sign, and Blumberg's sign were not found to be risk factors for complicated acute appendicitis in our study (Table 2).

*Adjusted for all variables: age, sex, leukocytes, previous medication, clinical characteristics, time to emergency visit, and time between first symptom and surgical act.

** p-value significant <0.05

OR: Odds Ratio 95 %: CI = 95 % Confidence Interval

Discussion

This study shows an association between the presence of complicated acute appendicitis (CAA) and various factors such as leukocytosis, a delay of more than 24 hours to emergency care, and a time from the onset of the first symptom to the surgical act between 24-48 hours and greater than 49 hours.

In our research, pediatric patients with leukocytosis had an OR of 2.79 for presenting with CAA. This is consistent with a study in Trujillo, where the OR was 2.39 (95% CI 1.04-5.51; p=0.0038) <sup>5 ➤
5. Doraiswamy NV. Leucocyte counts in the diagnosis and prognosis of acute appendicitis in children. Br J Surg. 1979;66(11):782–4. doi:10.1002/bjs.1800661109</sup> , and another study in northern Peru, which found an OR of 7.36 (95% CI 1.66-32.76; p=0.003) <sup>6 ➤
6. Zouari M, Abid I, Sallami S, Guitouni A, Ben Dhaou M, Jallouli M, et al. Predictive factors of complicated appendicitis in children. Am J Emerg Med. 2017;35(12):1982–3. doi:10.1016/j.ajem.2017.06.049</sup> . A study in India also indicated that leukocyte counts above 15,000/ml increase the likelihood of CAA. Our study used a cutoff of 11,000/ml for leukocytosis, and another study with a similar cutoff observed an OR of 16.38 (95% CI 1.836-146; p=0.012) <sup>7 ➤
7. Álvarez Ramos YV. Aspectos epidemiológicos de apendicitis aguda en cirugía pediátrica del Hospital Regional de Ayacucho 2016-2017. Univ Peru Los Andes [Internet]. 2019 [cited January 5, 2022]; Available at: http://repositorio.upla.edu.pe/handle/20.500.12848/1018</sup> . Additionally, a leukocyte count of 14,000/ml or higher was a predictor of CAA with an OR of 2.07 (p<0.001) <sup>5 ➤
5. Doraiswamy NV. Leucocyte counts in the diagnosis and prognosis of acute appendicitis in children. Br J Surg. 1979;66(11):782–4. doi:10.1002/bjs.1800661109</sup> .

It has been proposed that leukocytosis may indicate a prolonged inflammatory response due to delayed diagnosis and inadequate treatment at referral centers <sup>8 ➤
8. Li J, Xu R, Hu D-M, Zhang Y, Gong T-P, Wu X-L. Effect of Delay to Operation on Outcomes in Patients with Acute Appendicitis: a Systematic Review and Meta-analysis. J Gastrointest Surg. 2019;23(1):210–23. doi:10.1007/s11605-018-3866-y</sup> . Leukocytes play a crucial role in defense against bacteria, and their elevated count may be a marker of infectious complications and sepsis <sup>9 ➤
9. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990;132(5):910–25. doi:10.1093/oxfordjournals.aje.a115734</sup> . Although leukocytes may be normal in advanced stages of the disease, an elevated count can be indicative of prognosis <sup>10 ➤
10. Narsule CK, Kahle EJ, Kim DS, Anderson AC, Luks FI. Effect of delay in presentation on rate of perforation in children with appendicitis. The American Journal of Emergency Medicine. 2011;29(8):890–3. doi:10.1016/j.ajem.2010.04.005</sup> . In our study, 92.5% of children with leukocytosis had CAA, while 68.7% with leukocytosis had uncomplicated acute appendicitis.

Patients with a time from the onset of symptoms to the surgical act of 24-48 hours had an OR of 2.25, and those with a time greater than 49 hours had an OR of 3.01 for CAA. Additionally, children with a delay to emergency care of more than 24 hours had an OR of 1.72 for CAA. Further studies have shown that symptoms lasting more than 72 hours are associated with an increased risk of complicated appendicitis <sup>11 ➤
11. Álvarez Ramos YV. Aspectos epidemiológicos de apendicitis aguda en cirugía pediátrica del Hospital Regional de Ayacucho 2016-2017. Univ Peru Los Andes [Internet]. 2019 [cited January 5, 2022]; Available at: http://repositorio.upla.edu.pe/handle/20.500.12848/1018</sup> . Duration of symptoms greater than 24 hours has been confirmed as a predictor of complications <sup>12 ➤
12. Lazo Oblitas M. Factores asociados a apendicitis aguda complicada en pacientes pediátricos de la ciudad del Cusco, 2018. Univ Nac San Antonio Abad Cusco [Internet]. 2019 [cited January 5, 2022]; Available at: http://repositorio.unsaac.edu.pe/handle/20.500.12918/4038</sup>

It has also been observed that the duration of symptoms influences the risk of perforation and necrosis, with an increased risk associated with prolonged times <sup>13 14 15 ➤ ➤ ➤
13. Hernández-Cortez J, León-Rendón JLD, Martínez-Luna MS, Guzmán-Ortiz JD, Palomeque-López A, Cruz-López N, et al. Acute appendicitis: a literature review. Cir Gen. 2019;41(1):33–8.
14. Doraiswamy NV. Progress of acute appendicitis: a study in children. Br J Surg. 1978;65(12):877–9. doi:10.1002/bjs.1800651214
15. Wina IAS, Hamid S, et al. Perforated Appendicitis: Contributing Risk Factors and Outcome in Children at Gezira National Center of Pediatrics Surgery (2016-2017). Clin Surg [Internet]. 2021 [cited January 5, 2022];6(1). Available at: http://www.clinicsinsurgery.com/abstract.php?aid=7086</sup> .

The duration of symptoms, especially those lasting more than 48 hours, has been associated with a higher risk of perforation and necrosis, with a significant increase in risk when symptoms persist for more than 72 hours <sup>16 17 ➤ ➤
16. Siddique K, Baruah P, Bhandari S, Mirza S, Harinath G. Diagnostic accuracy of white cell count and C-reactive protein for assessing the severity of paediatric appendicitis. JRSM Short Rep. 2011;2(7):59. doi:10.1258/shorts.2011.011025
17. Williams RF, Blakely ML, Fischer PE, Streck CJ, Dassinger MS, Gupta H, et al. Diagnosing ruptured appendicitis preoperatively in pediatric patients. J Am Coll Surg. 2009;208(5):819–25; discussion 826-828. doi:10.1016/j.jamcollsurg.2009.01.029</sup> . The literature suggests that prolonged symptom duration increases the likelihood of severe complications, although there is no consensus on the exact threshold for this risk <sup>22 ➤
22. Peng Y-S, Lee H-C, Yeung C-Y, Sheu J-C, Wang N-L, Tsai Y-H. Clinical criteria for diagnosing perforated appendix in pediatric patients. Pediatr Emerg Care. 2006;22(7):475–9. doi:10.1097/01.pec.0000226871.49427.e</sup> .

A limitation of this study is that it does not allow for establishing the temporal relationship between risk factors and the development of CAA, nor does it determine causality. Additionally, variables such as C-reactive protein (CRP) and neutrophils were not considered. However, the findings provide an overview of CAA in patients from a pediatric hospital in Lima.

Conclusion

The research reveals a significant association between leukocytosis and an increased risk of developing complicated acute appendicitis in children. Additionally, the results indicate that delays exceeding 24 hours, both in surgical emergency care and in the interval from the onset of the first symptom to surgery, considerably increase the likelihood of presenting with complicated acute appendicitis. These findings underscore the importance of a prompt and effective medical response to minimize complications in pediatric patients with acute appendicitis. Leukocytosis is highlighted as a key predictive factor, and there is a need to optimize diagnostic and treatment times to improve clinical outcomes.