Abstract
Background:
Acute appendicitis is the most common cause of acute abdomen encountered in general surgical practice, with the life time risk of 7–9 %. While early treatment usually prevent complications, perforated appendicitis remains a serious concern leading to higher morbidity, longer hospital stay .
Objectives:
To determine clinical, demographic, laboratory, and radiological predictors of perforation in adults with acute appendicitis.
Methods:
This retrospective cohort study included 200 patients diagnosed with acute appendicitis and treated at a major teaching hospital between January 2018 and December 2022. Patients were categorized into perforated and non-perforated based on intra-operative and histopathological findings. Data on demographics, co-morbidities, symptom duration, laboratory markers, imaging results, complications, and hospital stay were collected. Multivariate logistics regression was applied to identify independent predictors of perforation.
Results:
Acute appendicitis was more prevalent among patients in their second decade of life (44%) and more common in males (56%) than females (44%). Perforation occurred in 20% of cases. Risk factors significantly associated with perforation include old age, delayed presentation (>48 hours; co-morbidities, particularly diabetes). Elevated WBC count (>18.000\mm3) with negative shift and increased C-reactive protein level. Ultrasound showed modest diagnostic accuracy, while Computed Tomography (cCT) scan outperformed ultrasound in detecting perforation (sensitivity: 92 vs. 65%). Postoperative complications and hospital stay were significantly higher in patients with perforated appendicitis (P-value < 0. 05).
Conclusion:
Delayed presentation, elevated inflammatory markers, old age, and co-morbidities are strong, independent predictors of appendiceal perforation. Early diagnosis and prompt surgical intervention, especially in patients with known risk factors, are crucial to prevent complications such as perforation and minimize hospital stay.
Keywords: acute appendicitis, perforation, risk factors complications
Introduction
Acute appendicitis is the most common surgical emergency encountered in general surgical practice worldwide with the life time incidence of approximately 7–9% in the general population[1] Progression to perforation carries significant clinical and economic consequences. In adults, perforation rates range from 15 and 30% and are associated with serious complications such as peritonitis, prolonged hospital stay, increased morbidity and mortality of up to 5% compared to less than 1% in non-perforated cases[2]. Most cases of complicated appendicitis begin as simple appendicitis, often due to delayed or missed diagnosis.[1,3]
Despite advancements in diagnostic imaging and the availability of inflammatory markers, the timely identification of patients at high risk for perforation remains a challenge. Delayed diagnosis and intervention frequently contribute to complications, particularly among vulnerable populations such as the elderly and immunocompromized, who may present with atypical or non-specific symptoms[3,4].
A number of demographic, clinical, laboratory and radiological factors have been implicated as potential predictors of appendiceal perforation in adult. Demographic factors such as extremes of age, female sex, and socioeconomic barriers are often linked to delayed presentation and diagnosis[4]. Clinical indicators including symptoms duration of more 48 hours, fever above 38.5ºC, and localized abdominal tenderness are well recognized. Laboratory markers including leukocytosis (>16 000 cells/µL) and elevated C-reactive protein (CRP; >50 mg/L) are also strongly associated with an increased risk of perforation. Radiological findings such as appendiceal diameter greater than 10 mm, the presence of an appendicolith, and periappendiceal fluid have also been shown to predict perforation[5]
Nevertheless, diagnosis is often delayed due to the diverse clinical presentations, especially among high-risk populations. As a result, the incidence of complicated appendicitis – including perforated and gangrenous forms – remains high, even with widespread use of advanced imaging modalities and laparoscopic evaluations[6,7].
Previous studies have largely examined isolated predictors of perforation without fully addressing the combined impact of co-morbidities, health care disparities, and the multifactorial nature of the disease[8]. This aim of this study is to provide a comprehensive analysis of demographic, clinical, laboratory, and radiological variables associated with perforation. By doing so, we seek to emphasize the importance of early recognition and intervention and to identify strategies to reduce the incidence of perforation through a better understanding of its key predictive factors.
Patients and methods
This retrospective cohort study was conducted at the department of surgery in Basra Teaching Hospital, Iraq, over a 5-year period (January 2018 to December 2022). Ethical approval was obtained from the Institutional Review Committee, and the study was registered in the Research Registry in compliance with the STROCSS 2021 guidelines. A total of 200 consecutive adult patients aged between 18 and 60 years who underwent emergency appendicectomy for clinically suspected acute appendicitis were included. The sample size was determined using a power analysis based on previously reported perforation rate of 15–25%. With α = 0.05 and β = 0.2 (80% power), a minimum of 186 patients was required to detect a 10% difference in perforation rates between risk groups. Therefore, our cohort of 200 patients was considered adequate. Patients with appendicular mass, generalized peritonitis from another cause, or those scheduled for interval appendicectomy were excluded to avoid confounding. Selection bias was minimized by including consecutive cases. Diagnostic bias was reduced by confirming all intra-operative findings with histopathological examination.
Clinical and demographic data (age, sex, duration of symptoms, time to surgery, co-morbidities, pregnancy status, and drugs used) were extracted from electronic records. Laboratory investigations included complete blood count and CRP. Modified Alvarado score (MANTRELS) was used to support diagnosis. Ultrasonography and contrast-enhanced CT were used where indicated.
All patients underwent either laparoscopic (majority) or open Appendicectomy (Grid-iron incision). Prophylactic antibiotics was given 30–60 minutes before incision. Patients were classified intra-operatively into non-perforated and perforated appendicitis, with histopathology used as confirmatory evidence.
The primary outcome was the identification of risk factors for appendiceal perforation. Secondary outcomes included postoperative complications and length of hospital stay.
Data were analyzed using SPSS Version 22. Descriptive statistics were expressed as ±SD for continuous variable and proportions for categorical variables. Comparison between groups were made using X2 or Fisher exact test for continuous variables. Univariate and multivariate logistic regression were performed to determine independent predictors of perforation. Odds ratio (OR) with 95% confidence interval (95% CI) were reported. A P-value < 0.05 was considered statistically significant.
Results
During the study period, 200 patients underwent appendicectomy for acute appendicitis. The mean was 31.8 ± 9.6 years (range 18–60). Of these, 112 (56%) were male and 88 (44%) female. Male-to-female ratio 1.3:1 (Table 1).
Table 1.
Age and sex distribution by perforation status
| Age | Non perforated appendicitis (n = 160) | Perforated appendicitis (n = 40) | Total (n = 200) | Male | Female | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| No. | % | No. | % | No. | % | No. | (%) | No. | (%) | |
| 18–20 | 47 | 23.5 | 4 | 10 | 51 | 25.5 | 27 | 13.5 | 24 | 12 |
| 21–30 | 54 | 27 | 6 | 15 | 60 | 30 | 33 | 16.5 | 27 | 13.5 |
| 31–40 | 36 | 18 | 9 | 22.5 | 45 | 22.5 | 25 | 12.5 | 20 | 10 |
| 41–50 | 15 | 7.5 | 11 | 27.5 | 26 | 13 | 16 | 8 | 10 | 5 |
| 51–60 | 8 | 4 | 10 | 25 | 18 | 9 | 9 | 4.5 | 9 | 4.5 |
| Total | 160 | 80 | 40 | 20 | 200 | 100 | 112 | 56 | 88 | 44 |
Overall, 40 patients (20%) had perforated appendicitis confirmed intra-operatively and histopathologically. Patients with perforation were significantly older (42.8 ± 8.1 vs. 23.6 ± 7.4 years, P < 0.01) and more frequently presented late (>48 hours from symptoms onset: 70% vs 3.7%, P < 0.001). Migratory abdominal pain (92%), anorexia (76%), nausea/vomiting (68%), and fever ≥38ºC were common presenting symptoms. On examination, right iliac fossa tenderness (87%) and rebound tenderness (74%) were most frequent. Laboratory investigations showed significantly higher WBC count in perforated appendicitis [16 800 (IQR 10 100–18 600) vs. 14 600 (9200–17 300), P = 0.003]. CRP levels were higher in the perforated group (median 9.7 vs. 3.4 mg/L), and the difference, however, was not statistically significant (P = 0.11). Ultrasound detects perforation in 24 patients (sensitivity 65%, specificity 80%). CT scans, performed in 57% patients, demonstrated markedly higher diagnostic accuracy (sensitivity 92%, specificity 95%; Tables 2 and 3)
Table 2.
Patient’s clinical and demographic characteristics
| Non perforated appendicitis (No. = 160) | Perforated Appendicitis (No. = 40) | P value | |||
|---|---|---|---|---|---|
| Age, mean (years) | (18–53) | 23.6 | 42.8 | 24–60 | <0.01 |
| Male sex, n (%) | 88 | 55 | 26 | 65 | 0.331 |
| Symptoms onset to admission (hours) | 18.9 ± 4 | 34.6 ± 2 | <0.001 | ||
| Localized tenderness, n (%) | 142 | 88.75 | 32 | 80 | 0.021 |
| Rebound tenderness, n (%) | 123 | 76.9 | 29 | 72.5 | 0.043 |
| White blood cell count, median (IQR) | 14.600 | 9.200−17.300 | 16.800 (10.100–18.600) | 0.003 | |
| C-reactive protein median (IQR) | 3.4 | 0.7–6.4 | 9.7 | 3.2−16.6 | 0.113 |
| High Alvardo scores (≥7) n (%) | 133 | 83.1 | 28 | 70 | 0.019 |
| Positive ultrasonography. n (%) | 87 | 54.4 | 26 | 65 | 0.032 |
| Positive CT scan, n (%) | 26/ 34 | 76.5 | 18/23 | 78.3% | 0.041 |
| Admission to operation time (hours) | 9.5 | 4–18 | 6 | 4–12.5 | 0.003 |
| Hospital stay (days) | 2.5 | 1–3.5 | 6.5 | 4–8.5 | <0.01 |
| Complications rate, n (%) | 12 | 7.5 | 8 | 20 | 0.018 |
Table 3.
Risk factors for perforated appendicitis
| Risk factors | Perforated | Non perforated | P-value | ||
|---|---|---|---|---|---|
| Appendicitis (no.40) | Appendicitis (no.160) | ||||
| No. | % | No. | % | ||
| Extremes of age (<20 or >60 years) | 18 | 45 | 67 | 41.9 | <0.05 |
| Delayed presentation (>48 hours) | 28 | 70 | 6 | 3.7 | <0.001 |
| Fever (> 38 ºC, n (%) | 9 | 22 | 10 | 6.2 | <0.01 |
| WBCs >18 000/mm3, n (%) | 3 | 7.5 | 1 | 0.6 | 0.014 |
| Co-morbidities (DM, HT, and IHD), n (%) | 33 | 82 | 72 | 45 | <0.01 |
| Pregnancy, n (%) | 4 | 10 | 2 | 1.2 | <0.05 |
| Steroid use, n (%) | 4 | 10 | 1 | 0.6 | <0.01 |
The mean admission to operation interval was shorter in the perforated group (6.0 vs 9.5 hours, P = 0.003), reflecting clinical emergency and urgency. However, hospital stay was significantly longer (6.5 vs. 2.5 days, P < 0.01). Complication rates were higher in perforated appendicitis (52.5% vs. 16.9, P < 0.01), with complications being surgical site infection (12.5%), intra-abdominal abscess (10%), and wound dehiscence (7.5%; Table 4).
Table 4.
Complications in perforated and non-perforated appendicitis
| Complications | Perforated appendicitis | Non perforated appendicitis | ||
|---|---|---|---|---|
| No. | % | No. | % | |
| Wound infection and SSI: Surgical Site Infection | 5 | 12.5 | 3 | 1.9 |
| Intra-abdominal abscess | 4 | 10 | 2 | 1.3 |
| Wound dehiscence /incisional hernia | 3 | 7.5 | 2 | 1.3 |
| Enterocutaneous fistulas | 2 | 5 | 0 | 0 |
| Ileus | 4 | 10 | 1 | 0.6 |
| UTI: Urinary Tract Infection | 2 | 5 | 0 | 0 |
| Chest infection | 1 | 2.5 | 0 | 0 |
| Total complication | 21 | 52.5 | 8 | 5 |
On univariate analysis, significant risk factors included extremes of age (<20 and >60 years), delayed presentation (>48 hours), fever >38ºC, WBC >18 000/mm2, co-morbidities (diabetes, hypertension, and ischemic heart disease), pregnancy, and steroid use (all P < 0.05).
Multivariate regression identified older age (OR 1.31, 95% CI 1.12–1.54, P < 0.01), delay presentation (OR 3.35, 95% CI 2.11–5.63, P < 0.001), elevated WBC count (OR 1.17, 95% CI 1.09–1.33, P = 0.004), C-reactive protein (OR 1.88, 95% CI 1.24–2.2.54, P = 0.002), and co-morbidities (OR 2.99, 95% CI 1.89–5.43, P < 0.001) as independent predictors of perforation (Table 5).
Table 5.
Univariate and multivariate analysis
| Variable | Univariate analysis | Multivariate analysis | ||||
|---|---|---|---|---|---|---|
| OR* | 95% CI | P value | OR | 95% CI | P value | |
| Age (years) | 1.043 | 1.02–1.02 | <0.01 | 1.31 | 1.12–1.54 | <0.01 |
| Male sex) | 1.37 | 0.72–1.2.34 | 0.23 | - | - | - |
| Symptom onset to till admission (hours) | 4.77 | 2.93–7.51 | 0.001 | 3.35 | 2.11–5.63 | <0.001 |
| WBC count (/mm3) | 1.09 | 1.02–1.17 | 0.01 | 1.17 | 1.09–1.33 | 0.004 |
| C-reactive protein (mg/L) | 1.33 | 1.11–1.59 | 0.01 | 1.88 | 1.24–2.54 | 0.002 |
| Co-morbidities | 4.64 | 2.43–6.77 | <0.001 | 2.99 | 1.89–5.43 | <0.001 |
| High Alvarado scores (≥7) | 1.83 | 0.91–3.44 | 0.34 | |||
| Positive ultrasonography | 1.45 | 0.88–2.88 | 0.35 | |||
| Positive CT scan | 3.36 | 1.29–5.13 | 0.003 | |||
| Hospital stay (days) | 2.24 | 1.55–4.21 | <0.01 | |||
OR, odds ratio; CI, confident interval.
Discussion
Acute appendicitis remains one of the most common surgical emergencies worldwide. Although most cases can be managed successfully with timely surgical intervention, perforated appendicitis continues to pose major clinical challenges due to its association with higher morbidity, prolonged hospitalization, and serious complications such as peritonitis and sepsis[2,9–11]. This retrospective study analyze risk factors associated with perforation in adults with acute appendicitis and compare our findings with those of previously published studies in trial to identify several key clinical, demographic, and diagnostic predictors of perforation.
Age also emerged as independent predictors of perforation[12,13]. In our cohort, patients older than 40 years were significantly more likely to experience perforation, with the incidence rising further after 50 years. This observation is consistent with studies of Franz et al[14] and Yamini et al[15] who attributed the higher risk in older patients to atypical or equivocal clinical presentation, altered immune responses and the presence of co-morbidities. Although the overall incidence of appendicitis is highest among younger patients (second and third decades of life), our findings confirm that the perforated cases occur disproportionately in older adults.
With respect to sex differences, our study observed a slight female predominance among perforated cases. However, gender did not remain a significant predictor after multivariate analysis. This observation is in agreement with that of Temple et al[16], whereas Roh et al[11] reported higher risk in females, possibly due to diagnostic overlap with gynecological conditions.
Inflammatory biomarkers were also strongly associated with perforation. Both leukocytosis and CRP were significantly more frequent in patient with perforated appendicitis. Nearly 90% of patients with perforation demonstrated elevation of both markers, underlining their diagnostic value in risk stratification. Our findings corroborate those of Andresson et al[17] and Ibrahim et al[18] who demonstrated the predictive accuracy of combing elevated WBC and CRP for complicated appendicitis.
Diagnostic imaging further highlighted the differences ion accuracy, ultrasound has a moderated diagnostic performance (sensitivity 65%, specificity 80%) which is consistent with prior studies by Fu J et al[19] and Kim et al[20]. Operator dependency, overlapping bowel gas, and patient body habitus are well-recognized limitations. In contrast CT scan showed excellent accuracy (sensitivity 92%, specificity 95%), confirming its role as the gold standard for evaluating perforated appendicitis. Our findings align with those of Iamwat J et al[21] and Zhang et al[22].
Another significant factor was the presence of co-morbidities, particularly diabetes mellitus and hypertension which were associated with an increased risk of perforation. This can be explained by altered immune responses, impaired pain perception, and delay diagnosis in diabetic patients. Similar associations were reported by Panahi et al[17] emphasizing the importance of heightened vigilance in patients with chronic medical conditions.
As expected postoperative complications were significantly more common in patients with perforation, surgical site infection (12.5%) and intra-abdominal abscess (10%) were the most frequent complications, leading to prolong hospital stay of 6.5 days compared to 2.5 days in non-perforated cases. These findings are in line with Burak et al[23], who also reported higher complication rates and prolonged hospitalization in perforated appendicitis.
The main limitations of this study were retrospective in nature conducted at a single center study. The analysis is subjected to inherent biases. Furthermore, the relatively small number of perforated cases may have limited the statistical power of subgroup analyses and reduced the robustness of multivariate model. Larger prospective multicenter studies are recommended to strengthen the validity generalizability of findings.
Conclusion
Perforated appendicitis remains a major clinical concern, as it is associated with higher morbidity, longer hospital stays, and increased risk of postoperative complications, underlying the need for early diagnosis and prompt surgical intervention. Our study highlights that delayed presentation, older age, elevated inflammatory markers, and the presence of co-morbidities are most important predictors of appendiceal perforation. While CT scanning remains the most reliable diagnostic tool, clinical awareness continues to play a central role, particularly in high-risk groups such as elderly and diabetic patients. Furthermore, improving prehospital care, ensuring the use of reliable diagnostic tools, and adopting structured management protocols can play a crucial role in lowering the incidence of perforation and enhancing overall patient outcomes. Although limited by its retrospective single-center design, this study adds to the growing body of evidence emphasizing the importance of timely presentation in improving outcomes for patients with acute appendicitis. Larger multicenter prospective studies are required to further validate these findings and support the development of more targeted clinical approach.
Acknowledgements
None.
Footnotes
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 26 November 2025
Contributor Information
Furat Shani Aoda, Email: furat.aoda@uobasrah.edu.iq.
Sura Saeed Abood, Email: surasky2003@gmail.com.
Ibrahim Falih Noori, Email: dr.ibraheemfns@gmail.com.
Ethical approval
This study was approved by ethical committee of Basra Medical College.
Consent
Written informed consent was obtained from the patient for publication of this randomized controlled study and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Sources of funding
None, self-funding.
Author contributions
Study conception and design and data acquisition: F.S.A. and S.S.A. Statistical analysis, interpretation of result, and manuscript drafting by I.F.N.
Conflicts of interest disclosure
Authors declare no any conflict of interest.
Research registration unique identifying number (UIN)
Research Registration: Researcregistry: http://www.researchregistry.com. Unique identifying number (UIN): unique identifying number is researchregistry10515. Hyperlink: https://www.researchregistry.com/browse-the-registry#home/.
Guarantor
The authors are the sole guarantors for this work.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Data availability statement
The data used during the current study are available from the corresponding author upon request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data used during the current study are available from the corresponding author upon request.