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178 Original Article 1 2 3 Nandhini. N.E , Ponnudhali. D , Evangeline Jones INTRODUCTION: he most common cause of acute abdomen in young adults in acute appendicitis. Delay in diagnosis and surgery for this T condition may lead to various complications like perforation, abdominal abscess, urinary retention, small bowel obstruction and peritonitis causing an increase in morbidity and even mortality of the patients. Incidence of perforated appendicitis in 1 adults is about 13-37% . Every investigation that can contribute towards a diagnosis of appendicitis 2 is valuable to emergency surgeon . Address for correspondence: Dr.D.Ponnudhali, Associate Professor, Department of Biochemistry, Vinayaka Missions Kirupananda Variyar Medical College, Salem. Email id: [email protected] Ph. No: 9443171055. 1 Final year Postgraduate Student, Dept. of Biochemistry, Vinayaka Missions's Kirupananda Medical College, VMRF(DU) Salem, TN. 2 Associate Professor, Dept. of Biochemistry, Vinayaka Missions's Kirupananda Medical College,VMRF(DU) Salem, Tamilnadu. 3 Professor and HOD, Vinayaka Missions's Kirupananda Medical College, Department of Biochemistry, Salem, VMRF(DU) Tamilnadu . Bilirubin - A Predictor Of Appendiceal Perforation National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018 http://dx.doi.org/10.31975/NJBMS.2018.8402 ABSTRACT Introduction: Acute appendicitis is the most common abdominal emergency. Any delay in the diagnosis and treatment, could result in life threatening complications like perforated appendicitis. Though non-specific tests like WBC count, C reactive protein are routinely done, they are not of much diagnostic value. Recent studies have shown that increase in pre-operative serum bilirubin levels could predict the occurrence of perforated appendicitis. Aims and objectives: 1) To assess the serum bilirubin (Total, Direct, Indirect) levels in acute and perforated appendicitis. 2) To look for any associated changes in liver enzymes. 3) To analyze the sensitivity and specificity of serum bilirubin and its utility as a diagnostic/ predictive marker of perforated appendicitis. Materials and methods: A Retrospective study - Medical records of sixty patients who had underwent open appendicectomy during the last one year were scrutinized and all the relevant information noted . 30 patients who underwent surgery for simple appendicitis formed group 1. 30 patients who underwent surgery for perforated appendicitis formed group 2. Their pre-operative laboratory serum bilirubin values and other liver parameter values were collected and analyzed. All the above parameters were compared between two groups using independent student 't' test and ROC curve obtained for Bilirubin ,with SPSS 23 software. Results: Total bilirubin levels were significantly increased in patients with perforated appendicitis (p=.000) compared to patients with simple appendicitis. Similar increase in serum direct and indirect bilirubin levels (p=.000) were noticed in perforated appendicitis patients. Total Bilirubin (cut-off: 0.80mg/dl) has sensitivity 80% and specificity 75%. Conclusion: Assessing serum bilirubin levels pre-operatively could have significant value in predicting appendicular perforation. Serum bilirubin being an inexpensive and routinely done test in all labs, with its high sensitivity and specificity, better qualifies as a diagnostic marker for perforated appendicitis even in a rural care centre. Key words: Serum total bilirubin, acute appendicitis, Alvarado's score, perforated appendicitis

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Page 1: Nandhini. N - NJBMSnjbms.in/uploads/19/5751_pdf.pdf · 2019. 2. 2. · Nandhini. N.E1, Ponnudhali. D2, Evangeline Jones3 INTRODUCTION: he most common cause of acute abdomen in young

178

Original Article

1 2 3Nandhini. N.E , Ponnudhali. D , Evangeline Jones

INTRODUCTION:he most common cause of acute abdomen

in young adults in acute appendicitis.

Delay in diagnosis and surgery for this Tcondition may lead to various complications like

perforation, abdominal abscess, urinary retention,

small bowel obstruction and peritonitis causing an

increase in morbidity and even mortality of the

patients. Incidence of perforated appendicitis in 1

adults is about 13-37% . Every investigation that

can contribute towards a diagnosis of appendicitis 2is valuable to emergency surgeon .

Address for correspondence:

Dr.D.Ponnudhali, Associate Professor, Department of Biochemistry, Vinayaka Missions Kirupananda Variyar Medical College, Salem. Email id: [email protected] Ph. No: 9443171055.

1Final year Postgraduate Student, Dept. of Biochemistry, Vinayaka Missions's Kirupananda Medical College, VMRF(DU) Salem, TN. 2Associate Professor, Dept. of Biochemistry, Vinayaka Missions's Kirupananda Medical College,VMRF(DU) Salem, Tamilnadu. 3Professor and HOD, Vinayaka Missions's Kirupananda Medical College, Department of Biochemistry, Salem, VMRF(DU) Tamilnadu .

Bilirubin - A Predictor Of Appendiceal Perforation

National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018

http://dx.doi.org/10.31975/NJBMS.2018.8402

ABSTRACT

Introduction: Acute appendicitis is the most common abdominal emergency. Any delay in the diagnosis and treatment, could result in life threatening complications like perforated appendicitis. Though non-specific tests like WBC count, C reactive protein are routinely done, they are not of much diagnostic value. Recent studies have shown that increase in pre-operative serum bilirubin levels could predict the occurrence of perforated appendicitis.

Aims and objectives:

1) To assess the serum bilirubin (Total, Direct, Indirect) levels in acute and perforated appendicitis.

2) To look for any associated changes in liver enzymes.

3) To analyze the sensitivity and specificity of serum bilirubin and its utility as a diagnostic/ predictive marker of perforated appendicitis.

Materials and methods: A Retrospective study - Medical records of sixty patients who had underwent open appendicectomy during the last one year were scrutinized and all the relevant information noted . 30 patients who underwent surgery for simple appendicitis formed group 1. 30 patients who underwent surgery for perforated appendicitis formed group 2. Their pre-operative laboratory serum bilirubin values and other liver parameter values were collected and analyzed. All the above parameters were compared between two groups using independent student 't' test and ROC curve obtained for Bilirubin ,with SPSS 23 software.

Results: Total bilirubin levels were significantly increased in patients with perforated appendicitis (p=.000) compared to patients with simple appendicitis. Similar increase in serum direct and indirect bilirubin levels (p=.000) were noticed in perforated appendicitis patients. Total Bilirubin (cut-off: 0.80mg/dl) has sensitivity 80% and specificity 75%.

Conclusion: Assessing serum bilirubin levels pre-operatively could have significant value in predicting appendicular perforation. Serum bilirubin being an inexpensive and routinely done test in all labs, with its high sensitivity and specificity, better qualifies as a diagnostic marker for perforated appendicitis even in a rural care centre.

Key words: Serum total bilirubin, acute appendicitis, Alvarado's score, perforated appendicitis

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179

surgery for simple appendicitis. Group 2: 30

patients who underwent surgery for perforated

appendicitis.

We collected LFT reports from records of 60

patients who were admitted with acute abdomen

out of which 30 patients were found to have

perforated appendicitis and 30 patients were found

to have simple appendicitis without any perforation

or gangrenous changes during surgery. Patients

were excluded from the study if they did not have

LFTs performed on admission, if they had a history

of confirmed hepatitis or liver disease or if they

were known to have persistently deranged LFTs.

Patients undergoing interval appendectomies,

appendectomies for other indications and patient

with negative appendectomies confirmed on

histological report were excluded from the study.

Other exclusion criteria were patient with risk

factors for hepatic disease such as alcoholism, a

history of viral hepatitis, Gilbert's disease, Dubin-

Johnson syndrome, benign recurrent intra-hepatic

cholestasis, and other documented biliary,

hemolytic or liver diseases associated with

hyperbilirubinemia.

STATISTICAL ANALYSIS:

Statistical analysis was done using the software

SPSS version 23 and data expressed as mean ± SD.

Differences in mean between the 2 groups were

analyzed using independent t test. Comparisons

were made between two groups of patients: those

with simple acute appendicitis and those with

appendiceal perforation. Mean levels of bilirubin,

and other LFTs were compared between groups.

The sensitivities, specificities, positive predictive

values and negative predictive values of serum

Various markers such as WBC count are identified

for diagnosing acute appendicitis. WBC count is

not specific for acute appendicitis and CRP may be

only significantly raised once perforation takes 3place . So these markers are used along with

various diagnostic scores such as Alvarado score,

Modified Alvarado score, Pediatric Appendicitis

score(PAS) for diagnosing acute appendicitis. But

none of them evaluates the risk of perforation in 4acute appendicitis . Though various imaging

modalities like computed tomography (CT) scan,

magnetic resonance imaging (MRI) and

ultrasonography may help in early diagnosis of

perforated appendix, they may not be readily

available in many health centers and also time 5, 6,7,8consuming .

In such condition clinical and laboratory

investigations may be the only, cheaper and readily

available options for diagnosis. Recent studies

have shown that elevated serum bilirubin is a useful

predictor of appendiceal perforation. The present

study was conducted to assess relationship between

appendicular perforation and serum bilirubin

levels, which could aid in preoperative diagnosis of

perforated appendicitis.

MATERIALS AND METHODS :

Study Design: Our study had been conducted in

Government Hospital, Bhavani and Vinayaka

Missions's Kirupananda Variyar Medical College

Hospital, Salem. It was a retrospective study

conducted in 60 patients admitted for

appendicectomy surgery during the period of

August 2016- July 2017. They were divided into 2

groups. Group 1:30 patients who underwent

Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis

National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018

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Table 2 : Mean and standard deviation for other

liver parameters in patients with acute

appendicitis without perforation (group 1) and

acute appendicitis with perforation (group 2)

The ROC curve analysis for serum total bilirubin

levels was done, with the Area Under the Curve

(AUC) being 0.825. The sensitivities, specificities,

PPVs and NPVs for different cut-off levels of

serum bilirubin were tabulated. At the optimum

cut-off level -0.8 mg/dl of serum total bilirubin,

sensitivity and specificity were 80% and 75%

respectively. Figure 1 depicts the ROC Curve of

total bilirubin.

Table 3 depicts the cut off values of serum total

bilirubin with their sensitivity, specificity, positive

predictive value (PPV) and negative predictive

value (NPV)

Table 3: Sensitivity and Specificity of serum

total bilirubin

180

bilirubin for both simple acute appendicitis and

perforated appendicitis was calculated. The

receiver operating characteristic (ROC) curve for

bilirubin was obtained

RESULTS :

The Bilirubin levels (total, direct, indirect) and

other liver parameters were analyzed in 30 patients

with simple appendicitis and 30 patients with

perforated appendicitis. The mean and standard

deviations of bilirubin (total, direct, indirect)

levels are depicted in Table 1.

There is a significant increase in the total bilirubin

levels (1.0 ± 0.28 mg/dl) in group 2 patients,

compared to the patients (0.61 ± 0.18 mg/dl) in

group 1 (p=0.001). There is a significant increase in

the serum direct and indirect bilirubin levels (0.30

± 0.13 mg/dl, 0.73 ± 0.19mg/dl,p=0.001) in group 2

patients, compared to the patients in group 1 (0.16 ±

0.08 mg/dl ,0.44 ± 0.16mg/dl,p=0.000).

Table 1: Mean and standard deviation for

Bilirubin in patients with acute appendicitis

without perforation (group 1) and acute

appendicitis with perforation (group 2).

*P value <0.05 is considered significant.

We compared the other liver function tests in both

the groups. There was not any significant

difference and they were with in normal limits in

both the groups. Table 2 depicts the other liver

functions tests in group 1 and group 2.

National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018

Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis

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181

Lipopolysaccharides associated with E. coli can

affect hepatocyte uptake and bile acid secretion15.

The patients with perforated appendicitis, show a

proinflammatory cytokine and nitric oxide –

triggered cholestasis by impairing hepatocellular 16

and bile duct function.

In our study we have found that patients with

perforated appendicitis had hyperbilirubinemia

with no changes in enzyme levels.There are few 17,18

other studies, having reported similar findings.

A retrospective analysis conducted by Atahan et al.,

found that symptom duration (p=0.002), total

bilirubin (p=0.000) and elevated leucocyte counts

(p=0.011) were significant independent variables

for identifying acute perforated appendicitis 19

against the suppurative ones .

A retrospective cohort study performed by Kaser

etal., in two centers compared the efficacies of

hyperbilirubinemia, CRP, leucocyte count and age 20as markers of perforated appendicitis . They came

to the conclusion that hyperbilirubinemia is a

statistically significant marker of perforated

appendicitis.

We have also assessed the AUC in ROC curve

analysis to determine the appropriate levels of

serum bilirubin at which it identifies perforated

appendicitis. As the AUC for total bilirubin is >0.8 ,

it can be considered as a marker to predict the

occurence of perforation among patients with acute

appendicitis. At the cut-off level of 0.8mg/dl, serum

total Bilirubin has a sensitivity of 80% and

specificity of 75%. Its utility as a predictive

biomarker has to be confirmed by further

prospective studies conducted in larger

populations.

Fig 1. ROC Curve for total bilirubin

DISCUSSION:

Acute appendicitis appears to be the most common

cause for “Acute Surgical abdomen”with

appendicular perforation being the most significant 9 ,10 ,11 ,12complication . The major organisms

commonly seen in normal appendix as well as acute

appendicitis are Eschericia coli, Bacteroids fragilis 13and various facultative anaerobes .

In acute appendicitis and perforated appendicitis

there is a compromised wall integrity resulting in 14following changes .

National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018

Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis

Acute appendicitis/ appendicular perforation

Translocation of bacterial endotoxins/cytokines(from appendicular lumen to portal system thereby liver)

Alters the physiology of biliary excretion.

Induces intrahepatic cholestasis

Hyperbilirubinemia

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182

CONCLUSION:

It is evident that Serum Bilirubin has a remarkable

role in identifying patients presenting with

perforated appendicitis. Serum Bilirubin with all its

beneficial attributes, is quite cheap, feasible and an

easily available laboratory test even in peripheral

health care centers. Hence it could be a useful

biomarker either alone or in combination with other

radiological methods, in the preoperative diagnosis

of perforated appendicitis.

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Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis

Received on: 18.04.2018 Revised on: 15.05.2018 Accepted on: 18.05.2018