P-ISSN: 2808-5957

E-ISSN: 2808-6724

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1957

SODIUM LEVELS AND LEUKOCYTE LEVELS AS PREDICTOR

FACTORS IN CASES OF PEDIATRIC PERFORATED APPENDICITIS

INTRODUCTION

Acute appendicitis is a general surgical emergency among children (Almaramhy, 2017).

Acute appendicitis usually affects children and adolescents aged 10 to 20 years, but even so, this

does not rule out the possibility of the disease occurring at other ages. Acute appendicitis is rare

in children of preschool age and is often diagnosed at the perforation stage. Compared to non-

perforated appendicitis, perforated appendicitis has a significant effect on postoperative outcomes

in the presence of an increased rate of complications (up to 39%) such as abscesses or inflammation

perforated appendicitis was also assessed at Dr. M. Djamil Hospital by Alhamda et al. (2022) and

found that as many as 59.8% of children with acute appendicitis experienced perforation. The rate

of perforated appendicitis in children ranges around 30% but can be much higher for younger

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1958 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

children (Zvizdic et al., 2021). Complete appendicitis has a positive correlation with younger age

groups so it is much more frequent in children less than 5 years of age (Neogi et al., 2022).

Enforcement of the diagnosis of acute appendicitis is quite different in a child. Although as

many as 33% of affected children may come with abdominal pain in the lower right quadrant,

nausea, and vomiting, the child may show atypical or delayed symptoms (Chandrashekar et al.,

misdiagnosis rate ranges from 28 to 57% in children aged 2 to 12 years and is close to almost

100% in children under 2 years old (Almaramhy, 2017; Yang et al., 2019). When the diagnosis is

established, perforation may already occur in 30%-75% of children, with young children at higher

risk (Chandrashekar et al., 2018).

Perforated appendicitis is defined as the presence of visible holes in the appendix or the

presence of a free appendix duct inside the abdomen where this event brings significant morbidity

in the child population and can lead to the occurrence of intra-abdominal abscesses (Chandrashekar

et al., 2018; Howell et al., 2018). Appendix perforation causes diffuse peritonitis or local

appendicular abscess. Diffuse peritonitis is more common in younger children, due to the

underdeveloped omentum, while children of older age are relatively protected by a well-developed

perforation. 10 Distinguishing perforated and non-perforated patients are very important given the

influence of perforation diagnosis on patient management (Yang et al., 2019).

Leukocyte count is the most frequently used laboratory examination in diagnosing

appendicitis. Moderate leukocytosis (15,000/mm3) is usually the earliest sign of inflammation of

the appendix. The number of leukocytes over 18,000/mm3 can be associated with the incidence of

complementary appendicitis (Sahbaz et al., 2014). A previous study was conducted by

Chandrashekar et al in 2018 on predictors of perforated appendicitis in 108 patients and found that

the average number of leukocytes and neutrophils was found to be higher in patients with

perforated appendicitis (Chandrashekar et al., 2018). The same was discovered by Yang et al in

2019 in 1895 children, in which higher leukocyte counts and lower serum sodium levels were

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1959 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

with several clinical variables were associated with the risk of perforation however if they stood

alone, leukocytes could not predict the incidence of perforation. Other results regarding the role of

leukocytosis in the prediction of perforation were also put forward by Dickinson et al and obtained

leukocytosis in acute appendicitis patients did not distinguish the incidence of perforation

(Dickinson et al., 2017).

uncomplicated appendicitis. The pathogenesis behind the relationship between complementary

appendicitis and hyponatremia remains uncertain, but new evidence suggests IL-6 has a role in

osmoregulation in intra-abdominal inflammation, leading to the release of vasopressin (Anand et

al., 2022).

Anand et al. (2022) in their meta-analysis study said that hyponatremia has the potential to

be used as a biochemical marker in the diagnosis of complementary appendicitis in the pediatric

population. Previously, Lindestam et al. (2020) also conducted a study on children aged 1-14 years

with acute appendicitis and found a strong association between low sodium concentrations and the

incidence of perforation. The results related to sodium levels in the incidence of perforation were

quite varied where Duman et al. (2022) conducted a retrospective study from Turkey with a total

higher the possibility of perforation (Alhamda et al., 2022). However, in this study, no comparison

between sodium and leukocytes was considered as a predictive factor even though leukocyte

examination is also a routine examination carried out in appendicitis cases and is also known to be

a predictor that was first used in appendix perforation cases. Therefore, researchers are interested

in conducting a study with the title "Sodium Levels and Leukocyte Levels as Predictor Factors in

Cases of Pediatric Perforated Appendicitis."

METHOD

This research is a quantitative study. The method used in this study was analytical

observational with a cross-sectional approach to see the difference in sodium and leukocyte levels

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1960 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

study sample is the part of the population that meets the inclusion criteria and has no exclusion

criteria.

This research instrument is a record of medical records of pediatric patients diagnosed with

appendicitis at RSUP Dr. M. Djamil Padang. The type of data used is secondary data, that is, pre-

existing data without going through the results of research. Secondary data in the study were

patients with a diagnosis of appendicitis. The data collected were in the form of patient

demographic data and laboratory records (Sodium and leukocytes) as well as complications of

appendicitis (Perforation) data management and analysis.

The data that has been collected will be processed through the following process: Editing,

which is to improve data quality and eliminate data doubts. Editing is done by checking the

completeness of the data filling again. What is considered is the completeness of patient

demographic data in the form of age and gender and laboratory data in the form of sodium and

leukocyte levels as well as writing and uniformity of units of measure. Coding, providing code to

the data that has been obtained by using numbers to make it easier to analyze data. Tabulating,

entering data into tables, and arranging numbers so that the number of cases can be calculated in

criteria and did not have exclusion criteria. After the sample is collected, data collection is carried

out regarding age, gender, sodium levels, leukocyte levels, complications of appendicitis

(Perforation), and actions from the patient's medical records.

Characteristics of Children with a Diagnosis of Acute Appendicitis Perforation and Non-

Perforation

In this study, 67 patients (60%) experienced acute perforated appendicitis (60%) and 45 non-

perforated patients (40%). It was found that the majority of incidences of appendicitis with

perforation in children aged 6-11 years (37 people, 55%), male sex (45 people, 67%),

hyponatremia (61 people, 91%), leukocytosis (58 people, 86.5%) with laparotomy appendectomy

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1961 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

to be normal (39 people, 87%), most leukocytosis (28 people, 62%), and were acted on more with

laparoscopic appendectomy (27 people, 60%).

Relationship of Sodium Levels with the Incidence of Perforated Appendicitis in Children

There was a statistically meaningful relationship between sodium levels and the incidence of

Perforation

In this study, data on age, gender, sodium levels, leukocyte levels, and surgical procedures

were taken in patients and then patient characteristic data were separated between appendicitis

patients without perforation and perforated appendicitis.

Based on the results of the study, it was found that the patients who had perforated

appendicitis were mostly aged 6-11 years. It is different from what was found by Zvizdic et al.

(2021) where they got the highest cases of perforated appendicitis in the age group under 5 years.

the younger the child's age, the greater the risk of perforation. In the study, it was stated that the

incidence of perforation had an inverse linear relationship with age, where patients aged less than

though the incidence of perforation is higher. The higher incidence of perforation in toddlers is

due to the thin wall structure so that in the event of infection it is more prone to rupture and cause

perforation (Almaramhy, 2017; Howell et al., 2018).

The most sex in perforated appendicitis is male (45 people, 67%). This is following what

was found by Zvizdic et al. (2021) in which the study conducted on perforated appendicitis, 58.3%

of the sample was male. In the previous year, Guss and Richards (2000) also conducted research

on perforated appendicitis and found that most patients were male. Augustin et al. (2011) said the

reason more men than women experience perforation is that the perception of pain in women is

higher so that it is more likely to convey the pain so that it does not drag on into complications.

In perforated appendicitis, most patients experience hyponatremia (91%) which is the

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1962 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

occurrence of hyponatremia in patients with perforated appendicitis is caused by the release of

cytokines from the perforated inflammatory tissue. A known cytokine is IL-6. These cytokines can

cross the blood-brain barrier (BBB) which triggers the release of antidiuretic hormone (ADH).

Nonosmotic release of ADH causes reabsorption of excess free water in the kidneys and causes

dilutional hyponatremia (Anand et al., 2022).

that more leukocyte levels will be recruited into the inflammatory tissue in patients with

perforation (Yamazaki et al., 2021).

Open appendectomy is the most therapeutic option performed in perforated appendicitis,

namely 57 people (85%), while in appendicitis without perforation, in patients most

appendectomies with laparoscopy are performed (27 people, 60%). Open appendectomy through

McBurney's incision has been considered the technique of choice in dealing with perforation cases

for more than a century. Appendix perforation can cause the spread of feces and purulent material

in the abdominal cavity, therefore open appendectomy is preferred for centuries. However,

nowadays laparoscopy is beginning to be used as a therapy in perforated appendicitis with

advantages such as shorter length of hospitalization and fewer analgesic needs.

patients was 130.55 ± 4.29 while in non-perforated appendicitis, sodium levels were obtained at

138.42 ± 3.54. These results are following the findings of Pogorelić et al. (2021) which compared

sodium values in perforated and non-perforated appendicitis patients.

In this study, the average sodium level in perforated appendicitis patients was 132.2 mmol/L

and in non-perforated appendicitis patients was 139.2 mmol/L. In this study, a significant

relationship was found between sodium levels and perforation events. Another study was also

found by Kim et al. (2015) that found lower sodium levels in patients with perforated appendicitis.

Different results obtained by Sheen et al. (2022) were that there was no significant relationship

between hyponatremia and perforated appendicitis in the child group. However, in the adult group,

a significant relationship was found between sodium and perforation. In this study, the number of

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1963 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

Receiver operating characteristic (ROC) curve analysis was performed to assess the best

cutoff for perforated appendicitis prediction and values for under-the-curve (AUC) area,

sensitivity, and specificity were given on average. After analysis, a sodium cutoff of 134.5 mmol/L

was obtained, which had a sensitivity of 91% and a specificity of 91% for the incidence of appendix

perforation. This result is similar to the findings of Pogorelić et al. (2021) who received a cutoff

also researched the best limit for prediction of obtaining a higher sodium prediction value of

≤137.5 mEq/L.

Although an accurate etiology for hyponatremia in patients with complementary appendicitis

has still not been identified, persuasive data are supporting the role of pro-inflammatory cytokines,

such as IL-6, IL-1β, etc., in the non-osmotic release of antidiuretic hormone (ADH). IL-6 is a

natural immune cytokine that is closely related to the degree of inflammation. Researchers often

use IL-6 as an indicator of the degree of systemic inflammation. IL-6 plays an important role in

distinguishing cases of simple and advanced appendicitis. Cytokines circulate across the blood-

brain barrier (BBB) and act on the neurons of the supraoptic and paraventricular nuclei.

Furthermore, there is an activation of Janus tyrosine kinases-signal transducer and activator of

16,867 ± 6,468, while the average leukocyte level in non-perforated appendicitis was 12,505 ±

5,021. The T-test in this study obtained significant results related to the association of leukocytes

with the incidence of perforated appendicitis with a p-value of 0.000 where higher leukocytes were

associated with perforated appendicitis. Research by Yang et al. (2019) found something similar

where the appendix perforation group had higher leukocyte values than non-perforations (14,890

± 723 vs 12,650 ± 558), and this difference was also found to be statistically significant (p-value

= 0.03). Jung et al. (2017) also found a significant difference between the leukocytes of perforated

and non-perforated patients. In this study, the average leukocyte level of patients with perforation

was 16,500 cells/mm3 and in the non-perforated group was 13,200 cells / mm3. Loha et al. (2019)

also researched leukocyte levels and perforated appendicitis using median values. In the study, it

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1964 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

Different results were obtained by Turhan et al who found differences in leukocyte values

between perforated and non-perforated patients were not statistically meaningful (p-value 0.451)

(Turhan et al., 2022). Meta-analysis studies by Zhou et al. (2006) also found leukocytes to be

insensitive and unspecific in assessing the incidence of appendix perforation. In this study, it was

stated that leukocytes can be used as predictors of perforation when combined with CRP values

of Farné et al. (2021) where the cut-off of leukocytes that predicts the perforation event is 13,990

cells / mm3 with a sensitivity of 73% and a specificity of 72%. Research by Beltrán et al. (2007)

found higher values for leukocyte limits of 15,900 cells/mm3 with a sensitivity of 40% and a fairly

high specificity of 90% at a symptom duration of <12 hours. This leukocyte limit value increases

to 16,100 cells/mm3 at hours 13-24 with sensitivity also increased to 60%. At the 25-48th hour of

symptom onset, the cut-off of leukocytes increases to 16,500 cells/mm3 in predicting the

occurrence of perforation with a sensitivity that is also getting higher at 70%. Sensitivity and

specificity are best at determining the incidence of perforation obtained at a leukocyte limit value

of 16,900 cells/mm3 after 49 hours have passed from the onset. Jones et al. (2021) also said in

their literature review that leukocyte levels equal to and or above 17,000 cells/mm

were associated

with several other parameters as previously stated by previous studies (Yamazaki et al., 2021).

CONCLUSION

In this study, 67 (60%) patients experienced perforated appendicitis. This group was

dominated by the age group of 6-11 years, the male sex (55%), the results of labor hyponatremia

(91%), the results of labor leukocytosis (86.5%), and followed up with an open appendectomy

(85%). In the non-perforated appendicitis group (45 patients, 40%), the predominance was

possessed by the age group of 6-11 years (49%), the female sex (58%), the results of labor

normonatremia (87%), the results of labor leukocytosis (62%), and the action of laparoscopic

appendectomy (60%).

Sodium Levels and Leukocyte Levels as Predictor Factors in Cases of Pediatric Perforated Appendicitis

1965 | I n d o n e s i a n J o u r n a l o f M u l t i d i s c i p l i n a r y S c i e n c e , 2 ( 2 ) , N o v ,

2022

limit value that predicts the incidence of perforated appendicitis is ≤134.5 mmol/L with a

sensitivity of 91% and a specificity of 91%.

The relationship between leukocyte levels and perforated appendicitis in children was found

to be significant with a p-value of <0.05, which is 0.000. The average leukocyte level in perforated

appendicitis is 16,867 ± 6,468, while the average leukocyte level in non-perforated appendicitis is

Almaramhy, H. H. (2017). Acute appendicitis in young children less than 5 years: Review article.

Anand, S., Krishnan, N., Birley, J. R., Tintor, G., Bajpai, M., & Pogorelić, Z. (2022).

Araim, F., Shmelev, A., & Kowdley, G. C. (2022). Incidence of complicated appendicitis as a

Augustin, T., Cagir, B., & VanderMeer, T. J. (2011). Characteristics of perforated appendicitis:

Chandrashekar, S., Lokesh, M. G., & Avinash, S. R. (2018). Prevalence of perforated appendicitis

Dickinson, C. M., Coppersmith, N. A., & Luks, F. I. (2017). Early predictors of abscess

Duman, L., Karaibrahimoğlu, A., Büyükyavuz, B. I., & Savaş, M. Ç. (2022). Diagnostic value of