Article, Gastroenterology

Differentiation of exudate from transudate ascites based on the dipstick values of protein, glucose, and pH

a b s t r a c t

The aim of present study was to determine the reliability of the dipstick values (protein, glucose, and pH) for differentiation of exudate from transudate ascites in comparison with the serum-ascites albumin gradient as criterion standard. A total of 100 patients with ascites (58 males and 42 females; mean age, 55.6 +- 16.1 years) were studied for the different causes of ascites. Peripheral blood samples were obtained, and at the same time, the patients underwent paracentesis. There were 62 cases (62.0%) of transudate ascites and 38 (38.0%) of exudates ascites, based on serum-ascites albumin gradient. Using logistic regression, we found a dipstick equation (K = 0.012Protein - 0.012Glucose - 3.329pH + 23.498) to differentiate transudate (K b 0) from exudate (K N 0) ascites. The sensitivity, specificity, positive predictive value, and negative predictive value of dipstick equation to diagnose ascites as transudate and exudate were 93.8%, 94.4%, 96.8%, and 89.5%, respectively, and 94.4%, 93.9%, 89.5%, and 96.9%, respectively. The area under the receiver operating characteristic curve was 0.915 (95% confidence interval, 0.848-0.982; P b .001). We concluded that the dipstick can be an inexpensive, rapid, and simple option for categorizing ascites into transudate and exudate and can be used routinely for this purpose in clinical practice.

(C) 2013

Introduction

Ascites is defined as the pathologic accumulation of free fluid in the peritoneal cavity [1]. The development of ascites marks the onset of worsened prognosis and increased mortality in patients. Most patients (approximately 85%) with ascites in the United States have cirrhosis, whereas nonhepatic diseases cause most of the remaining cases [2]. A correct diagnosis of the cause of ascites is thus an important pillar in the care of a patient.

Abdominal paracentesis with appropriate ascitic fluid analysis is an early step in evaluating patients with ascites and classifying it as exudate or transudate [3,4]. This fluid is usually a transudate in patients with acute or chronic Liver failure, massive Liver metastasis, hypoalbuminemia, or heart failure, whereas it is an exudate in those with peritoneal carcinomatosis, peritonitis, or pancreatic ascites [5]. Several studies have been performed for differentiating the ascitic

* Corresponding author. Department of Emergency Medicine, Imam Hossein Hospital, Shahid Madani Ave, Emam Hosein Sq, Tehran 1617763141, Iran. Tel.: +98 2177558081; fax: +98 2177557069.

E-mail address: [email protected] (H.R. Hatamabadi).

fluid as either exudate or transudate. The serum-ascites albumin gradient (SAAG) has been proved superior to other parameters in categorizing ascites in several studies [2,5-9]. However, laboratory assessing of ascitic fluid and serum is not always available in some small outpatient setting, and sometimes, it cannot be done as in emergency basis.

Recently, many studies have proposed urinary reagent strips for a rapid diagnosis of infection in many body fluids such as ascitic fluid, so that using dipsticks reduced the time from paracentesis to a presumed diagnosis of Spontaneous bacterial peritonitis from a few hours to a few seconds [10-20]. Urine dipsticks are impregnated with reagents that indicate some feature of the liquid by changing color and are used to identify, for example, protein, blood, glucose, and pH in Urine samples [21-28]. On the other hand, there are differences between exudates and transudates ascites with respect to values of some Biochemical parameters. For instance, exudates are high in protein and have a low glucose level and a low pH, and transudates have low protein, normal glucose, and high pH [29]. Therefore, the objective of this study was to determine the reliability of the dipstick values (protein, glucose, and pH) for differentiation of exudate from transudate ascites in comparison with the SAAG as criterion standard.

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780 K. Heidari et al. / American Journal of Emergency Medicine 31 (2013) 779-782

Materials and methods

Table 1

The characterizations of patients with transudate and exudate ascites; mean (SD)

This cross-sectional study was done on 100 consecutive patients admitted with ascites to 2 educational hospitals, Tehran, Iran, over a 2-year period. Subjects signed their written informed consents before being included in this study. The study was approved by the Ethics Committee of Shahid Beheshti University of Medical Science.

The characteristics of the study population (including sex, age, cause of ascites, duration of ascites, and volume of ascites fluid) were collected via a questionnaire. Peripheral blood samples were obtained for cell counts and biochemical markers. At the same time, the patients underwent paracentesis, and immediately after the procedure, an amount of ascitic fluid was sent to the laboratory in tube for analysis of albumin, protein, glucose, and pH. Albumin was assessed with colorimetric methods, and conventional autoanalyzer was used to analyze protein, glucose, and pH. Remaining ascitic fluid was collected in

Total

(n = 100)

Male, n (%) 58 (58.0)

40 (64.5)

17 (47.4)

.070

Age (y) 55.6 +- 16.1

58.2 +- 14.5

51.3 +- 17.8

.063

Duration of ascites (mo) 2.6 +- 1.5

2.6 +- 1.6

2.7 +- 1.5

.634

Volume of ascitic fluid (L) 3.6 +- 2.1 Analysis of ascitic fluids

Dipstick

3.8 +- 2.3

3.2 +- 1.8

.238

Protein (mg/dL) 288.5 +- 200.2

197.6 +- 172.4

436.8 +- 147.8

b.001

Glucose (mg/dL) 334.5 +- 257.3

437.9 +- 258.7

165.8 +- 140.0

b.001

pH 7.6 +- 1.0

8.1 +- 0.7

6.7 +- 0.8

b.001

Laboratory

Protein (g/dL) 1.7 +- 1.1

1.4 +- 0.8

2.3 +- 1.4

b.001

Glucose (mg/dL) 130.1 +- 65.2

138.7 +- 71.5

116.1 +- 51.2

.093

pH 7.7 +- 0.9

8.1 +- 0.7

7.0 +- 0.8

b.001

Transudate (n = 62)

Exudate P

(n = 38)

a clean dry container and tested using a dipstick (Medi-Test Combi 11; Macherey-Nagel, Duren, Germany) for determination of protein, glucose, and pH. The strips had colorimetric scales (glucose [mg/dL]: negative, normal, 50, 150, 500, >=1000; protein [mg/dL]: negative, 30, 100, 500; pH: 5, 6, 7, 8, 9) and were read at 30 seconds for glucose and at 60 seconds for protein and pH. The procedure was the same as what the manufacturer described for urine. Each dipstick test was separately done by 2 persons who were blinded to all clinical information and laboratory results about the patient. If the result of 2 persons about each dipstick test was similar, then the value of test was used for analysis.

Calculating the SAAG involves measuring the albumin concentra- tion of serum and ascitic fluid specimens obtained on the same day and subtracting the ascitic fluid value from the serum value. A high gradient (>=1.1 g/dL) indicates that the ascites is transudate, and a low gradient (b 1.1 g/dL) indicates that ascites is exudate [8].

SPSS 20.0 (SPSS, Inc, Chicago, IL) software was used for statistical analysis. The Student t test and the Mann-Whitney U test were used for independent normally and nonnormally distributed continuous variables, respectively. Nominal variables were analyzed by means of ?2 test. Correlation between variables was evaluated by Pearson correlation analysis. Logistical regression analysis was used to differentiate exudate from transudate ascites using dipstick values (protein, glucose, and pH). Using logistic regression, the data of 67 patients (42 transudate and 25 exudates) were used to design the model (train group), and the remainder of the whole patients (20 transudate and 13 exudates) was used to test model (test group). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood rates, and area under receiver operating characteristic (ROC) curve were calculated. Significance was defined at the level of P b .05.

Results

We reviewed 100 patients with ascites, 58 males (58.0%) and 42 females (42.0%), with a mean age of 55.6 +- 16.1 years. The duration of ascites and volume of ascitic fluid was 2.6 +- 1.5 months and 3.6 +- 2.1 L, respectively. There were 62 cases (62.0%) of transudate ascites and 38 (38.0%) of exudates ascites, based on SAAG. The transudate group consisted of 45 cases (72.6%) with liver cirrhosis, 9 (14.5%) with chronic renal failure, and 8 (12.9%) with congestive heart failure. The exudate group comprised 25 cases (65.8%) of malignant abdominal tumor and 13 (34.2%) of Abdominal infection.

The characterizations of patients with transudate and exudate ascites were compared in Table 1. The transudates had significantly low protein level (197.6 +- 172.4 vs 436.8 +- 147.8 mg/dL, P b .001),

high glucose level (437.9 +- 258.7 vs 165.8 +- 140.0 mg/dL, P b .001),

and high pH (8.1 +- 0.7 vs 6.7 +- 0.8, P b .001) in comparison with the exudates using dipstick. There was a significant correlation between dipstick and Laboratory analysis of ascitic fluid with respect

to protein (r = 0.654, P b .001), glucose (r = 0.638, P b .001), and pH (r = 0.977, P b .001).

Using logistic regression, we found an equation (dipstick equa- tion) to differentiate transudate from exudate ascites based on dipstick values of 67 cases (train group):

K = 0.012Protein-0.012Glucose-3.329pH

+ 23.498 Dipstick equation

A negative value of K indicated that ascites was transudate, whereas a positive value of K indicated that ascites was exudate. Table 2 shows the performance of dipstick equation in categorizing ascites in test group, compared with the SAAG as criterion standard. The sensitivity, specificity, PPV, and NPV of dipstick equation to diagnose ascites as transudate and exudate were 93.8%, 94.4%, 96.8%, and 89.5%, respectively, and 94.4%, 93.9%, 89.5%, and 96.9%, respectively. Using the ROC curve, further analysis of these data calculating the area under curve was performed (Fig). The area under the ROC curve (AUC) was 0.915 (95% confidence interval, 0.848-0.982; P b .001).

Discussion

This study shows that ascitic fluid analysis by dipstick has a reasonable accuracy for ascites diagnosis. We found an equation (dipstick equation) to differentiate transudate from exudate ascites based on dipstick values of protein, glucose, and pH. We considered a transudate when the dipstick equation was negative, and sensitivity, specificity, PPV, and NPV were achieved 93.8%, 94.4%, 96.8%, and 89.5%, respectively. On the other hand, sensitivity, specificity, PPV, and NPV of positive dipstick equation results for exudate diagnosis were 94.4%, 93.9%, 89.5%, and 96.9%, respectively.

In a clinical setting, it is important to differentiate transudate from exudate ascites to plan diagnostic and therapeutic strategies [30,31]. Many studies have been performed for categorizing fluids into transudates and exudates. Although investigators suggested Light’s criteria [7,32,33], lactate dehydrogenase [34], bilirubin [35], and

Table 2

The performance of dipstick equation in categorizing ascites as transudate and exudate in test group

Dipstick equation

Transudate

Exudate

Sensitivity (%)

93.8

94.4

Specificity (%)

94.4

93.9

PPV (%)

96.8

89.5

NPV (%)

89.5

96.9

Positive likelihood ratio

16.9

15.6

Negative likelihood ratio

0.07

0.06

K. Heidari et al. / American Journal of Emergency Medicine 31 (2013) 779-782 781

Fig. The ROC curve at categorizing ascites causes as transudate and exudate using dipstick equation in test group.

cholesterol [36-38] as differentiating parameters, SAAG has been proved superior to other factors in categorizing ascites in several studies [2,5-9]. For instance, Boghratian et al [35] reported that SAAG is the best criterion (specificity, 0.9090; positive predictive value, 0.97; positive likelihood rate, 8.03). They found that bilirubin and lactate dehydrogenase ratio criteria had equivalent specificity (0.8333 and 0.8205, respectively), predictive positive value (0.54 and 0.55, respectively), and positive likelihood rate (4.09 and 4.30, respective- ly), which generally were better than fluid total protein and total protein ratio but not as predictive as SAAG.

However, there may be several hours delay in reporting results from the laboratory. In addition, laboratory assessing of ascitic fluid and serum is not always available in some small outpatient setting, and sometimes, it cannot be done as in emergency basis. Therefore, for the first time, we used dipstick as an inexpensive and rapid method for distinguishing ascitic fluid into transudates and exudates. dipstick urinalysis is used for detection of Leukocyte esterase, nitrites, protein, blood, glucose, and pH of urine sample. Many studies have recently suggested urinary reagent strip for a rapid diagnosis of infection in many body fluids such as ascitic fluid, whereas it was traditionally used for Prompt diagnosis of urinary tract infections [10-20].

A dipstick test for proteinuria is widely available. In a primary care setting, a positive standard dipstick test of urine in Hypertensive patients may indicate the presence of microalbuminuria with high specificity [39-42]. In addition, dipstick testing seems to be reliable in urinary screening for detection of glucose. Zamanzad et al [43] reported the sensitivity and specificity of 100% and 98.5%, respective- ly, for detection of glucose in urine sample. However, there was no information for detection of protein and glucose in ascitic fluid using dipstick. We found significant correlation between dipstick and laboratory analysis of ascetic fluid with respect to protein, glucose, and pH. In addition, protein, glucose and pH levels exhibited significant differences between transudative and exudative fluids, confirming the results of previous studies [29]. Transudative samples had significantly low protein levels, high glucose levels and high pH values in comparison with exudative samples.

The AUC is a measure of a model’s Discriminatory power. According to the observation by Swets et al [44], an AUC of 0.7 or higher is diagnostically useful. In our study, dipstick equation could discriminate ascites well (AUC, 0.915; 95% confidence interval, 0.848-

0.982; P b .001). According to our knowledge, there is no study to differentiate transudate from exudate ascites based on dipstick values of protein, glucose, and pH.

The real-time use of the model is not difficult. The number of hospitals that have an electronic medical record is growing rapidly. The data used by our model were the standard information routinely collected in a dipstick test. Once trained, the model could reside in the background of the clinical information systems. Once entered into the electronic record, these data could then be used by the model to generate the probability of the predicted outcome.

However, inherent limitations of the dipstick test include variability in interpretation between readers as well as results that may be affected by variable lighting conditions. In addition, we used a dipstick urinalysis for analyzing of ascitic fluid, whereas in urine sample, the protein and glucose contents are quite different.

In conclusion, we believe that the dipstick can be an inexpensive, rapid, and simple option for categorizing ascites into transudate and exudate and can be used routinely for this purpose in clinical practice. The good accuracy of this method along with its simplicity and the fact that it takes only 60 seconds to complete would translate into higher early detection rates and improved patients’ outcome. However, future studies using the same experimental set-up and a larger sample size should carry out in several centers to confirm the performance of different dipsticks in ascites diagnosis.

Acknowledgments

We thank Dr. Abdolrahimi for his kind editorial support for the manuscript. This article was based on a postgraduate thesis by Dr Amiri, which was successfully completed under the supervision of Dr Heidari and Dr Hatamabadi. This project was supported by a research grant from Shahid Beheshti University of Medical Sciences.

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