Introduction
Acute pancreatitis (AP) is a common cause of severe acute abdomen. Early diagnosis and precise grading of disease severity are important goals for the initial evaluation and management of AP. Due to the risk of rapid deterioration in severe AP, the assessment of severity becomes crucial to a clinician.[ 1 , 2 ] Several scoring systems and laboratory tests have been proposed to estimate the prognosis of AP.[ 3–5 ] However, the disadvantages associated with these scoring systems include delayed results (after 48 h of admission), the hassle of complicated calculations, and the need for ordering specific tests, some of which are expensive. Till date, no single serum marker can predict the severity or mortality in AP at admission. Red cell distribution width (RDW) is a parameter of the complete blood count test which is routinely performed in almost all patients at the time of admission.[ 6–9 ] Hypocalcemia has been associated with AP severity .[ 10–12 ] Both RDW and total serum calcium (TSC) are simple routine parameters related to inflammatory status and results of which are readily available. In our study, we assessed RDW and the ratio of RDW-to-TSC values in predicting the outcome of patients with AP.
Materials and Methods
This study was conducted on all patients diagnosed with AP at a tertiary care center. Consecutive sampling was used to enroll the patients. The inclusion criteria were as follows: Patients with age of more than 18 years, presenting within 5 days of onset of symptoms of AP, and with a minimum hospital stay of 24 h. According to the Revised Atlanta Classification (RAC) for diagnosing AP at least two of these criteria had to be present: typical clinical presentation including acute persistent abdominal pain, serum amylase exceeding three times the upper limit of normal (100 IU/L), and characteristic findings on abdominal ultrasonography and/or computed tomography. AP severity was also defined according to the RAC, based on the presence of single or multiple persistent organ failure (>48 h) and/or local complications. Organ failure was recorded which included cardiovascular, respiratory, and renal failures. The exclusion criteria included the patients on immunosuppressive therapy, active malignancy, chronic use of erythropoietin, recent transfusion history, pregnancy, or trauma as these conditions affected the RDW. Furthermore, patients with parathyroid disorders, the use of thiazides, or granulomatous disorders such as sarcoidosis were excluded as these affected the TSC levels.
The incidence rate of AP is 33.74 cases per 100,000 person years based on previous data.[ 13 ] On the basis of the formula: N = (Z 2 a × P × (1 − P )/d 2 , assuming the power of 80%, confidence level at 95%, and precision at 1.2%, the minimum sample size comes out to be 90. We included 94 cases in our study, fulfilling the minimum sample size criteria. The data obtained were evaluated for the parameters which included age, gender, etiology, symptoms, average hospital stay, organ failure, and AP-associated local/systemic complications. Serum calcium levels along with complete blood count which included RDW were done within the first 24 h of admission. In addition, data regarding treatment modality, i.e., medical management or invasive procedure (percutaneous catheter drainage or necrosectomy), were collected. Data pertaining to patient mortality were also recorded.
Appropriate statistical tests were applied to analyze the data. Data were described in terms of range, median interquartile range (IQR), frequencies (number of cases), and relative frequencies (percentages) as appropriate. To determine whether the data were normally distributed, a Kolmogorov–Smirnov test was used. Comparison of quantitative variables between the study groups was done using Analysis of Variance (Kruskal-Wallis Test) [Table 1 ] and Mann-Whitney U -test [Table 2 ] and for nonparametric and parametric data, respectively. Sensitivity, specificity, positive and negative predictive values, and accuracy of each method and its confidence interval (CI) (95% CI) were determined, besides the Youden Index (Sensitivity + Specificity – 1) (probability of correct classification) and determining the area under the ROC curve. A probability value (P value) <0.05 was considered statistically significant. All statistical calculations were done using SPSS (Statistical Package for the Social Science) SPSS 21 version (SPSS Inc., Chicago, IL, USA) and MedCalc statistical program for Microsoft Windows.
Table 1: Correlation of red cell distribution width , serum calcium, and red cell distribution width : total serum calcium to severity of acute pancreatitis
Observations and Results
This study was conducted on 94 patients who were diagnosed with AP at a tertiary care center. The following results were obtained from the collected data obtained within 24 h of hospitalization.
The median (IQR) age observed was 41 (31–55) years. Most of the patients (63.8%) were males while 36.2% were females. The most common symptom in patients with AP was pain abdomen (98.9%), followed by vomiting (37.2%). In our study, the most common cause of AP was biliary (46.8%), followed by alcohol (34.0%). The median (IQR) hospital stay duration for patients with mild, moderately severe, and severe pancreatitis was 8 (6–10) days, 14 (12–18) days, and 20 (14–39) days, respectively, with a P = 0.000 which is significant. In our study, 53.2% of patients had organ failure, out of which 47.9% had respiratory failure, 10.6% had renal failure, and 4.3% had cardiovascular failure. Out of the total 94 patients, 46.8% had mild pancreatitis and 27.7% had moderately severe pancreatitis while 25.5% had severe pancreatitis.
Diagnostic accuracies of red cell distribution width and total serum calcium -to-severity of acute pancreatitis
The median (IQR) RDW for mild, moderate, and severe pancreatitis was 13.20 (13.0–13.80), 15.56 (15.0–16.10), and 17.70 (17.10–18.28), respectively, while the median (IQR) RDW: TSC for mild, moderate, and severe pancreatitis was 1.58 (1.51–1.67), 2.10 (2.04–2.20), and 2.83 (2.68–3.0), respectively [Table 1 ]. RDW (Area under the receiver operating characteristic curve (AUROC): 0.997; P = 0.000 i.e., significant) and RDW:TSC (AUROC: 1; P = 0.000 i.e., significant) as depicted in Figure 1 , were major predictors of severe AP to a cutoff value of 16.25% (sensitivity - 100%; specificity - 97.1%, positive predictive value - 92.31%, negative predictive value - 100%, and Youden Index - 0.971) and 2.42 (sensitivity - 100%; specificity - 100%, positive predictive value - 100%, negative predictive value - 100%, and Youden Index - 1.00), respectively [Tables 3a -c ].
Table 2: Correlation of red cell distribution width , total serum calcium , and red cell distribution width : total serum calcium to the mortality of acute pancreatitis
Figure 1: AUROC of RDW and TSC for acute pancreatitis severity . AUROC: Area under the receiver operating characteristic curve; RDW: Red cell distribution width ; TSC: Total serum calcium
Table 3a: Area under the receiver operating characteristic curve of red cell distribution width and red cell distribution width : total serum calcium for the severity of acute pancreatitis
Table 3b: Correlation of red cell distribution width with severity of acute pancreatitis
Table 3c: Correlation of red cell distribution width and red cell distribution width : total serum calcium with the severity of acute pancreatitis
Diagnostic accuracies of red cell distribution width and total serum calcium with mortality in acute pancreatitis
The median (IQR) RDW for survivors and nonsurvivors was 14.60 (13.20–16.20) and 18.0 (17.80–18.40), respectively, while the median (IQR) RDW: TSC for survivors and nonsurvivors was 1.82 (1.58–2.22) and 3.0 (3.0–3.11), respectively [Table 2 ]. RDW (AUROC: 0.947; P = 0.000 i.e., significant) and RDW:TSC (AUROC: 0.975; P = 0.000 i.e., significant) as depicted in Figure 2 , were major predictors of mortality in AP to a cutoff value of 17.20% (sensitivity - 100%; specificity - 87.4%, positive predictive value - 38.89%, negative predictive value - 100%, and Youden Index - 0.874) and 2.9 (sensitivity - 100%; specificity - 96.6%, positive predictive value - 70%, negative predictive value - 100%, and Youden Index - 0.966), respectively [Tables 4a -c ]. The median (IQR) of RDW and RDW: TSC with different types of interventions among the study group is depicted in Table 5 . The overall mortality recorded in our study was 7.45%, whereas 85.1% of patients were discharged under stable conditions and 7.45% were discharged on request with stable vitals.
Figure 2: AUROC of RDW and TSC for acute pancreatitis mortality . AUROC: Area under the receiver operating characteristic curve; RDW: Red cell distribution width ; TSC: Total serum calcium
Table 4a: Area under the receiver operating characteristic curve of red cell distribution width and red cell distribution width : total serum calcium for acute pancreatitis mortality
Table 4b: Correlation of red cell distribution width with mortality of patients of acute pancreatitis
Table 4c: Correlation of red cell distribution width : total serum calcium with mortality of patients of acute pancreatitis
Table 5: Red cell distribution width and red cell distribution width : total serum calcium in different types of interventions in the study group
Discussion
AP is one of the most common surgical diseases which can cause severe acute abdomen. Most cases (80%–90%) are mild and usually managed with fluid resuscitation and supportive care. The remaining 10%–20% of patients with severe disease have either pancreatic necrosis or distant organ failure and usually require intensive care and possible operative intervention with a mortality rate of up to 40%. The early identification of potentially severe AP enables the selection of patients who may require a more intensive and invasive method of management than is appropriate in mild pancreatitis and can play a significant role in management decisions and in reducing the morbidity and mortality associated with severe AP. In previous studies, several AP scoring systems and laboratory tests have been proposed to estimate the prognosis of AP. Ranson’s score, Balthazar score, BISAP score, SARS score, Glasgow score, APACHE II, Marshall, and sepsis-related organ failure assessment scoring systems are different severity scoring systems studied in the past and proven to be indicators of the clinical severity . However, none of the above scoring systems are proven to be the precise indicators of adverse clinical outcomes. Individual parameters such as hematocrit (Hct), creatinine, serum blood urea nitrogen, C-reactive protein, D-dimer, procalcitonin levels creatinine, Hct, urinary trypsinogen-activation peptide, polymorphonuclear elastase, TNF-alpha, IL-1, and IL-6 have also been studied over the years to predict the severity of AP. Several clinical signs and imaging procedures have emerged in an attempt at early identification of pancreatic necrosis, monitoring of its progression, and assessment of the response to therapy. The ideal prognostic biomarker in AP should be clinically available, inexpensive, insensitive to inter-individual differences, and accurately predict severe cases upon admission. The search for such a biomarker is ongoing for decades and numerous promising candidates have been proposed. However, still, no marker has been able to predict complicated diseases with sufficient precision.
Most of the studies conducted previously have included only RDW as a predictor of the severity of AP, but our study includes additionally the ratio of RDW and TSC as a predictor of severity and mortality in AP. Till date, only one such study has been published worldwide by Gravito-Soares et al .[ 14 ] that includes the ratio of RDW and TSC. However, as their study had been conducted in Portugal, the demographics of the study were different from that of our study conducted in India. No other study with such parameters has been done in India.
This study aimed to assess two new early noninvasive predictors of severity and mortality in AP, namely RDW and RDW: TSC, which are easy to determine. Our study group’s mean age (43.32 years), gender distribution, and etiology are comparable to the study conducted by Peng et al .[ 15 ] In our study, 53.2% of patients had organ failure, out of which 47.9% had respiratory failure which is comparable to Marta Gravito-Soares et al .’s study.[ 14 ] In our study, RDW (AUROC: 0.997; P = 0.000 i.e., significant) and RDW:TSC (AUROC: 1; P = 0.000 i.e., significant) prove to be major predictors of severe AP to a cutoff value of 16.25% (sensitivity - 100%; specificity - 97.1%) and 2.42 (sensitivity - 100%; specificity - 100%), respectively. This is comparable to Marta Gravito-Soares et al . study[ 14 ] which concluded RDW (AUROC: 0.960; P < 0.001) was found to be a major predictor of severe AP to a cutoff value of 13.0% (sensitivity - 92.7%; specificity - 84.3%) and RDW:TSC (AUROC: 0.973; P < 0.001) as a major predictor of severe AP to a cutoff value of 1.4 (sensitivity - 96.3%; specificity - 84.3%).
In our study, RDW (AUROC: 0.947; P = 0.000 i.e., significant) and RDW:TSC (AUROC: 0.975; P = 0.000) were also found to be major predictors of mortality in AP to a cutoff value of 17.20 (sensitivity - 100%; specificity - 87.4%) and 2.9 (sensitivity - 100%; specificity - 96.6%). This again is comparable to Marta Gravito-Soares et al .’s study[ 14 ] where RDW (AUROC: 0.842; P < 0.001) was found to be a major predictor of mortality in AP to a cutoff value of 14% and RDW: TSC too as a major predictor of mortality in AP to a cutoff value of 1.7. We observed a mortality rate of 7.45% which is comparable to Marta Gravito-Soares et al .[ 14 ] and Peng et al .[ 15 ] studies.
Summary and Conclusion
In this study, we found that RDW and RDW: TSC are good prognostic predictors of severity and mortality in patients with AP. The tests are convenient to perform and the results are quickly available, with easy and reliable interpretation. Increased RDW and RDW: TSC can be used as new indicators of severity and mortality in patients with AP. However, this study has a few limitations such as the study was applied to a single tertiary care center and had a limited number of patients. Thus, multicentric and comparative cohort studies with larger sample sizes are needed to further confirm the present findings. Second, the treatment given in the first 48 h at other primary centers may have affected the severity and mortality .
Ethical clearance
The study was approved by the Research and Ethics Committee of Dayanand Medical College and Hospital vide Reference No 4/57-2018.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
The authors especially thank all the medical and nonmedical staff of the surgery as well as the pathology department for their sincere work and cordial cooperation with this project.
References
1. Bradley EL 3rd. A clinically based classification system for
acute pancreatitis . Summary of the International Symposium on
Acute Pancreatitis , Atlanta, Ga, September 11 through 13, 1992. Arch Surg 1993;128:586–90.
2. Forsmark CE, Baillie J AGA Institute Clinical Practice and Economics Committee AGA Institute Governing Board. AGA Institute technical review on
acute pancreatitis . Gastroenterology 2007;132:2022–44.
3. Gomatos IP, Xiaodong X, Ghaneh P, Halloran C, Raraty M, Lane B, et al. Prognostic markers in
acute pancreatitis . Expert Rev Mol Diagn 2014;14:333–46.
4. Cho JH, Kim TN, Chung HH, Kim KH. Comparison of scoring systems in predicting the
severity of
acute pancreatitis . World J Gastroenterol 2015;21:2387–94.
5. Almeida N, Fernandes A, Casela A. Predictors of
severity and in-hospital
mortality for
acute pancreatitis :Is there any role for C-reactive protein determination in the first 24 hours?. GE Port J Gastroenterol 2015;22:187–9.
6. Evans TC, Jehle D. The red blood cell distribution width. J Emerg Med 1991;9 Suppl 1 71–4.
7. Wang D, Yang J, Zhang J, Zhang S, Wang B, Wang R, et al.
Red cell distribution width predicts deaths in patients with
acute pancreatitis . J Res Med Sci 2015;20:424–8.
8. Goyal H, Awad H, Hu ZD. Prognostic value of admission red blood cell distribution width in
acute pancreatitis :A systematic review. Ann Transl Med 2017;5:342.
9. Li Y, Zhao Y, Feng L, Guo R. Comparison of the prognostic values of inflammation markers in patients with
acute pancreatitis :A retrospective cohort study. BMJ Open 2017;7:e013206.
10. Shinzeki M, Ueda T, Takeyama Y, Yasuda T, Matsumura N, Sawa H, et al. Prediction of early death in severe
acute pancreatitis . J Gastroenterol 2008;43:152–8.
11. Hong W, Dong L, Huang Q, Wu W, Wu J, Wang Y. Prediction of severe
acute pancreatitis using classification and regression tree analysis. Dig Dis Sci 2011;56:3664–71.
12. Lee BJ, Kim CD, Jung SW, Kwon YD, Kim YS, Yim HJ, et al. Analysis of the factors that affect the
mortality rate in severe
acute pancreatitis . Korean J Gastroenterol 2008;51:25–33.
13. Xiao AY, Tan ML, Wu LM, Asrani VM, Windsor JA, Yadav D, et al. Global incidence and
mortality of pancreatic diseases:A systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol 2016;1:45–55.
14. Gravito-Soares M, Gravito-Soares E, Gomes D, Almeida N, Tomé L.
Red cell distribution width and
red cell distribution width to
total serum calcium ratio as major predictors of
severity and
mortality in
acute pancreatitis . BMC Gastroenterol 2018;18:108.
15. Peng T, Zuo X, Zhang Y, Wang C, Wu H. Assessment of red blood cell distribution width as an early predictor of persistent organ failure in patients with
acute pancreatitis . J Pancreas (Online) 2017;18:393–8.
