Appendiceal inflammation affects the length of stay following appendicectomy amongst children: a myth or reality?

Abstract

The effect of the severity of appendiceal inflammation on post-operative stay in children following appendicectomy has shown conflicting results. This study was conducted to determine the association between the severity of appendiceal inflammation and post-operative stay amongst children undergoing open appendicectomy. A retrospective cohort study was conducted at a District General Hospital for two years. A total of 204 patients were included in the study with an age range between 3 and 16 years. Females were 54.9% while the rest were male. Mean age was 12.5±3 years. The association of the severity of appendiceal inflammation and post-operative stay was assessed by multivariable Cox Proportional hazards model. Mean post-operative stay was 2.32 days (95% CI 2.14–2.51). Macroscopically perforated appendix, histological inflammation and post-operative complications were significantly associated with post-operative stay on univariable analysis (P<0.05). Whereas, the multivariable analysis showed that the post-operative stay was significantly prolonged only in case of either perforated appendix or post-operative complications while it remained unaffected by the histological inflammation.

Keywords

appendiceal inflammation / post-operative stay / paediatrics

Introduction

Appendicitis is the most common atraumatic abdominal disorder in the pediatric population [1]. Around 10% of the UK population develops acute appendicitis, with the commonest age group between 10 and 20 years [2]. Its incidence in children aged 0-4 years is 1-2 cases per 10 000 per year, which rises to 25 cases per 10 000 for children 10-17 years old [1]. A delay in the diagnosis of appendicitis can lead to various complications like perforation or abscess formation thus leading to prolonged post-operative stay, ultimately causing an increase in the financial burden on the healthcare system [3].

The pediatric appendicectomy is performed at the Specialized Paediatric Centers (SPC) as well as at the District General Hospitals (DGH) [4]. Literature review shows a wide variation in the length of post-operative hospital stay following open appendicectomy, but the evidence looking at the effect of the severity of appendiceal inflammation on the post-operative length of stay (LOS) is scarce. And that also shows conflicting evidence about the relationship between the severity of inflammation and the post-operative LOS [4-6].

This study aimed to determine if there is an association between the severity of appendiceal inflammation and the length of post-operative stay amongst children undergoing open appendicectomy.

Materials and methods

Study design and setting

This retrospective cohort study was conducted at William Harvey Hospital, Kent, UK. All Children aged 3–16 years, who underwent open appendicectomy between January 2007 to December 2008 were included. The details of admission till discharge were reviewed. Those with incomplete hospital records were excluded.

Data collection and study variables

Data were collected by a trained data collector on a pre-tested questionnaire uniformly for all the subjects. The study variables included:

Outcome (dependent) variable. It was the post-operative hospital stay (No. of days) after appendicectomy, i.e., the interval between the date of appendicectomy (surgery) and the date of discharge.

Exposure (independent) variables. Age, gender, duration of symptoms, perforated appendix and appendicular abscess at surgery, inflammation of appendix at histology and post-operative complications were taken as the independent variables.

Sample size

The total number of children who underwent appendicectomy was 219, out of which 15 had incomplete or missing hospital records. Therefore, 204 children were included in the study (Fig. 1).

Statistical methods

Data were analyzed in SAS version 9.1.2 [7], and SPSS version 14 [8]. Descriptive statistics were computed. Proportions were calculated for categorical variables, mean and standard deviation (SD) for continuous variables having normal distribution, median and inter quartile range (IQR) for continuous variables having skewed distribution. Mean post-operative stay was calculated by means of Kaplan-Meier curve. Univariable analysis was performed by conducting log rank test. Multivariable regression was done by Cox Proportional hazards (PH) model. A P value of 0.05 was considered significant. Age, gender, appendicular abscess and symptom duration were found to be the confounding variables (∆β percentage≥15%). These were adjusted in the final model. Time ratio was calculated by exponentiation of – (β). Those amongst whom the date of discharge from the hospital was not available were censored in the analysis.

Ethical considerations

The list of patient was created by using procedure specific trust coding. The data were anonymised by allocation of specific patient numbers and only the principal investigator had the password protected access. Once the analysis was completed, data were securely locked on the internally protected trust website.

Results

Out of the total of two hundred and four children 54.9% were female with a mean age of 12.5 years (SD 3 years). The mean duration of symptoms was 2.3 days (SD 2.8 days). Macroscopic findings included a perforated appendix in 32 (15.6%) while appendicular abscess in 43 (21.1%) patients. Histology showed normal appendix in 37 (18.1%), acute suppurative appendicitis in 135 (66.2%) and gangrenous appendicitis in 32 (15.7%). Post-operative complications developed in 23 patients (Table 1), the details of which have been previously published [9].

The mean post-operative stay calculated by Kaplan-Meier estimate was 2.3 days (95% CI 2.1 - 2.5 days). At univariable analysis, the inflammation of appendix at histology, perforated appendix and post-operative complications were significantly associated with a prolonged post-operative hospital stay (Table 2, Fig. 2a-2c). whereas, the appendicular abscess was marginally associated with a prolonged post-operative stay (Table 2, Fig. 2d).

The relationship of the grade of inflammation at histology with symptom duration, perforated appendix and complications was not found to be significant (likelihood ratio test P<0.05). Also the interaction of perforated appendix with symptom duration and complications and interaction of appendicular abscess with symptom duration and complications was not found to be significant (likelihood ratio test P<0.05).

The multivariable analysis showed that the post-operative stay in children having a perforated appendix was 1.7 (95% CI 1.07 - 2.69) times compared to those without perforation. The post-operative stay in children having acute suppurative appendicitis on histology was 1.39 (95% CI 0.96 - 2.03) times and that for gangrenous appendicitis was 0.89 (95% CI 0.34 - 2.3) times compared to those having a normal appendix at histology. The post-operative stay in children having post-operative complications was found to be 2.26 (95% CI 1.54 - 3.32) times compared to those having no post-operative complications. Age, gender, appendicular abscess and symptom duration were not significantly associated with post-operative stay on multivariable Cox PH model (Table 3).

Discussion

The diagnosis and management of appendicitis in children still poses a challenge in the present era [10]. This is owing to the atypical presentations among children which may lead to delay in diagnosis and increased morbidity [11]. Various factors that affect the post-operative hospital stay include patient’s age, symptom duration, type of operative procedure and the severity of macro or microscopic inflammation of appendix [12]. The LOS can be shortened by determining the factors that influence it.

To evaluate the effect of severity of appendicular inflammation on the LOS, we have utilized the same classification system as described by Kalliakmanis et al. for the intraoperative as well as histological inflammation of appendix [13]. Macroscopically, in acute suppurative appendicitis, the appendix becomes swollen and erythematous; while histologically, the inflammation extends into muscularis propria. With severe inflammation involving serosa, it presents with perforation with or without localized abscess. Both the perforated appendix and post-operative complications were found to be the independent predictors of prolonged post-operative stay in children undergoing open appendicectomy. The severity of inflammation of appendix at histology was noted to significantly influence the post-operative stay on univariable analysis. However, on multivariable analysis, the severity of microscopic inflammation as well as appendicular abscess did not have any significant association with the LOS.

The mean post-operative stay in children undergoing appendicectomy in our study was found to be consistent with another DGH [10]. A study by Nance et al. showed that median post-operative hospital stay in children with a perforated appendix (9 days) was significantly higher (P<0.001) than those without any perforation (3 days) [12], a finding that corroborates our results. Interestingly, similar finding has been observed in adults as well [14].

Children who developed post-operative complications also had a significantly longer hospital stay as compared to those without complications adjusting for age, gender, appendiceal inflammation at histology, appendicular abscess and a perforated appendix. Out of the 32 children who had a perforated appendix, 53.12% (n = 17) developed post-operative complications; highlighting a significant association between a perforated appendix and post-postoperative complications (P = 0.01) thus leading to prolonged LOS. Mallick et al. have also reported that complicated appendicitis is associated with a high rate of post-operative complications and a prolonged hospital stay [15]. This finding highlights the fact that timely diagnosis and treatment of appendicitis is crucial in reducing the risk of perforation [16], as well as post-operative complications, in turn leading to a shorter post-operative stay.

Our study has shown similar finding as reported by Whisker et al. that the post-operative stay is not affected by the severity of microscopic appendicitis on histology [4]. Though findings by Alexander and Foulds do not support it [5,6]. One of reasons for this discrepancy may be due to the fact that the studies concluding that there is no relationship between inflammation of appendix at histology and post-operative stay were conducted in UK, while the latter studies are from USA and New Zealand respectively [5,6]. Ethnic variability and the patient demographics may be responsible for this discrepancy. This needs further exploration.

Studies in adults have shown that the length of hospital stay increases with patient age [14]. This is not the case in children aged 3 - 16 years as found in this study. The post-operative stay remained unaffected by gender in both cases as well [14].

This study has an important clinical implication. In the era of credit crunch when the NHS has been given a tedious task to do massive savings, an early diagnosis of appendicitis can help prevent post-operative complications thus leading to a shorter post-operative stay and hence reducing the healthcare cost.

How can perforation (representing severe macroscopic inflammation) be picked up early in children? Our earlier study showed that symptoms duration as well as the temperature at presentation was significantly higher in children with a perforated appendix as compared to those with simple acute appendicitis [9]. Since the clinical presentation of children is variable [17,18] and a perforated appendix has serious sequelae, it is of utmost importance to utilize other investigations to reduce the diagnostic error [15,19]. Raised white cell count (WCC) and C-reactive protein (CRP) should prompt toward a serious pathology necessitating a quick decision making to prevent complications [9,20].

The strength of our study is that it took into account the potential confounders and adjusted for it in the Cox PH model to show the true association between the macro and microscopic severity of appendicitis and the post-operative stay. Moreover the entire patient journey was followed from their admission till discharge making it a strong design (cohort study) for looking at the above mentioned relationship. The sample size of this study was reasonable and demographic profile was comparable to the children presenting with appendicitis at the other DGH [4], thus these findings can be generalized to children aged 3–16 years who present with suspected appendicitis to the other district general hospitals in the UK.

Conclusions

Severe macroscopic inflammation of appendix in children leading to either a perforation or post-operative complications is significantly associated with a prolonged post-operative hospital stay, though it remains unaffected by the appendiceal inflammation at histology.

Conflict of interest

Drs. Khurram Siddique, Shirin Mirza and Gandra Harinath have no conflict of interests or financial ties to disclose.

References

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