© 2013, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(13)60101-0

 

 

Contributors: JTJ proposed the study. PJY performed research and wrote the first draft. PJY, HTH, and HJT collected and analyzed the data. All authors contributed to the design and interpretation of the study and to further drafts. JTJ is the guarantor.

Funding: This work was supported by a grant from the 2007 Inje University (0001200743900).

Ethical approval: No needed.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

 

 

 

 

 

(Hepatobiliary Pancreat Dis Int 2013;12:645-650)

 

KEY WORDS: acute pancreatitis; scoring system; pancreatic necrosis; organ failure

Acute pancreatitis is an inflammation of the pancreas with possible peripancreatic tissue and multiorgan involvement. It results from a complex process that has variable etiology and natural histories, and early identification of patients at high risk can be difficult. Most episodes of acute pancreatitis (80%) are mild and self-limiting, without sequelae. In 10%-20% of cases, however, severe disease develops and parts of the pancreas and surrounding tissue become necrotic. In such cases, the acute inflammatory response may progress to systemic inflammatory response syndrome and/or multiorgan failure resulting in death.^[1,2] Individual responses to pancreatic injury are highly variable and often unpredictable. Severe diseases should be predicted by careful ongoing clinical assessment, together with a multiple-factor scoring system and imaging studies.^{[1, 3, 4]} Several scoring systems can predict severe complications, but current methods of risk stratification for acute pancreatitis are complicated and require data that are not routinely collected on early stage.^[1] A new prognostic scoring system, the bedside index for severity in acute pancreatitis (BISAP), is a simple and accurate method for early identification of patients at risk of in-hospital death (Table 1).^{[1, 5, 6]}

 

The purposes of this study were to evaluate the usefulness of BISAP as an early severity scoring system and to compare BISAP with other scoring systems, including Ranson criteria, APACHE-II, and CT severity index (CTSI), and with biological markers, including C-reactive protein (CRP), hematocrit (Hct), and body mass index (BMI). And we also investigated the relationship between BISAP score and hospital stay.

 

 

The clinical, laboratory, and radiologic data for all patients admitted or transferred to our hospital from March 2007 through December 2010 with a diagnosis of acute pancreatitis were retrospectively reviewed. Up to 2 days of data for all patients were collected during the course of each patient's hospitalization. On rare occasions, not all the laboratory values or vital signs were available in patients included in the study who were transferred to our institution from outside hospitals. Twenty-seven patients whose data from the first 24 hours were missing were excluded from further analysis. The BISAP and APACHE-II scores were calculated using the data from the first 24 hours after admission, and Ranson score was calculated for those whose data were available within first 48 hours after admission. CTSI was calculated for patients who underwent contrast-enhanced computed tomography (CECT) within 7 days of admission. All CT scans were reviewed by radiologists specializing in abdominal imaging.

 

Diagnosis of acute pancreatitis was based on the presence of two of the following three features: 1) abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back); 2) serum amylase and/or lipase at least three times greater than the upper limit of normal value; and 3) characteristic manifestations of acute pancreatitis on CECT, less commonly MR imaging or transabdominal ultrasonography.

 

Acute pancreatitis was classified as mild or severe on the basis of organ failure (transient or persistent) and/or local complications such as peripancreatic fluid collections and infected necrosis. Organ failure including shock (systolic blood pressure <90 mmHg), pulmonary insufficiency (arterial PO₂ <60 mmHg in room air or the need for mechanical ventilation), and renal failure (serum creatinine level >2 mg/dL after rehydration or hemodialysis) persisted for more than 48 hours. Organ failure scores during hospitalization were calculated for all patients from the most extreme laboratory value or clinical measurement. Infected necrosis was defined as lack of enhancement of pancreatic parenchyma with abscess assessed by CECT.

 

Values of continuous variables are presented as medians and interquartile ranges, and categorical data are presented as proportions. The distributions of severity, necrosis, organ failure, and death by BISAP point score were assessed with the Cochran-Armitage trend test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for individual scoring systems. Receiver-operating characteristic (ROC) curves were examined for optimal BISAP, Ranson, APACHE-II, and CTSI scores for predicting severity, necrosis, organ failure, and death using cutoffs values. The predictive accuracy of each scoring system was measured by area under the receiver-operating curve (AUC). AUC comparisons were also performed among other scoring systems at a time using the nonparametric approach developed by DeLong et al.^[7] A P value of <0.05 was chosen to be significant for all tests given the Bonferroni correction conducted among the study cohort. Associations of BISAP with hospital day was analyzed by univariate linear regression. All statistical calculations were performed with SAS 8.1 (Cary, NC, USA).

 

 

From March 2007 through December 2010, 303 patients were admitted to the hospital with acute pancreatitis. Clinical characteristics and outcomes of all patients are summarized in Table 2.

 

The distributions of severe disease, pancreatic necrosis, organ failure, and death by BISAP score are presented in Table 3. The frequencies of BISAP scores 0-5 of severe pancreatitis were 3.8%, 3.7%, 24.4%, 53.8%, 100% and 0%, respectively. Trends for increasing severity, organ failure, and death rates with increasing BISAP score were statistically significant (P<0.05).

 

ROC curves for BISAP score predicting severe pancreatitis, necrosis, organ failure, and death yielded AUC of 0.80 (95% CI, 0.70-0.90), 0.47 (95% CI, 0.37-0.57), 0.93 (95% CI, 0.88-0.97), and 0.86 (95% CI, 0.71-1.00), respectively. AUCs for each scoring system predicting severe pancreatitis, pancreatic necrosis, organ failure, and death are shown in Table 4. The accuracy of BISAP as a predictor of severe pancreatitis was slightly greater than the accuracy of Ranson criteria (0.74; 95% CI, 0.64-0.85) and similar to the accuracy of APACHE-II (0.80; 95% CI, 0.69-0.91). But no statistical significance was found between BISAP and Ranson criteria (P=0.115) and between BISAP and APACHE-II (P=0.761). The AUC for BISAP predicting organ failure was as high as the AUC for APACHE-II (0.95; 95% CI, 0.91-0.99, P=0.204) and higher than the AUC for Ranson criteria (0.84; 95% CI, 0.76-0.92; P<0.05). The AUC for BISAP predicting mortality was not statistically different from the AUC for Ranson criteria (0.74; 95% CI, 0.57-0.91; P=0.242) and from the AUC for APACHE-II (0.87; 95% CI, 0.75-0.98; P=0.574). ROC curves for each scoring systems predicting organ failure are shown in Fig. 1. On the basis of highest sensitivity and specificity values generated from the ROC curves, the following cutoffs were selected for further analysis: BISAP score ≥2, Ranson criteria ≥3, APACHE-II ≥8, and CTSI ≥4. Using the above cutoffs, the sensitivity, specificity, PPV and NPV of different scoring systems in predicting severe AP, pancreatic necrosis, organ failure, and mortality are seen in Table 5.

 

We analyzed the accuracy of BISAP as a predictor of severe pancreatitis, necrosis, organ failure, and death in comparison with CRP, Hct and BMI, all well-known independent prognostic factors of acute pancreatitis. ROC curves for initial CRP predicting severe pancreatitis, necrosis, organ failure, and death yielded AUC of 0.69, 0.56, 0.80 and 0.72, respectively. There was no statistically significant difference between AUC for initial CRP and AUC for CRP after 48 hours, except that the AUC for initial CRP predicting organ failure was greater than that of CRP after 48 hours (0.60) (P<0.05). AUCs for CRP, Hct and BMI predicting severe pancreatitis, necrosis, organ failure, and death are shown in Table 6. AUCs for BISAP predicting severe pancreatitis, organ failure, and death were greater than those for CRP, Hct and BMI (P<0.05). We also found that increasing BISAP score was associated with increasing length of hospital stay (P<0.05) (Fig. 2).

 

 

In this study, we evaluated the usefulness of BISAP as an early marker of the severity of acute pancreatitis and compared the accuracy of 4 prognostic multi-factorial scoring systems. This study demonstrated that the accuracy of BISAP in predicting severe acute pancreatitis and death was similar to that of the other scoring systems, including Ranson criteria and APACHE-II, and there was a significant trend toward higher mortality with increasing BISAP score. Moreover, BISAP was more accurate in predicting severe pancreatitis, organ failure, and death than CRP, Hct and BMI. Higher BISAP score was associated with longer hospital stay.

 

BISAP has several important advantages as a prognostic scoring system for acute pancreatitis.^{[1, 5, 6, 8, 9]} Firstly, BISAP is simple to calculate.^{[1, 5, 6]} Ranson criteria and modified Glasgow criteria require data not routinely collected at the time of hospitalization, and both require 48 hours to complete.^{[1, 6]} APACHE-II, the most commonly used prediction scoring system, was initially designed to predict prolonged ICU treatment and includes a large number of parameters, some of which may not be relevant to prognosis of patients with acute pancreatitis.^{[1, 6]} BISAP, however, requires only physical examination, vital signs, laboratory data, and imaging for detection of pleural effusion that are commonly documented within 24 hours of presentation.^[5] Secondly, BISAP predicts in-hospital death in the early stages of disease.^[5]

 

The most remarkable result of this study is that BISAP score can be an early marker for organ failure. According to the revised Atlanta classification, local pancreatic complications and extrapancreatic organ failure determine the severity of acute pancreatitis.^[10] More recently, organ failure has been shown to be a much stronger predictor of mortality than local complications such as peripancreatic fluid collections and necrosis.^[4,10,11] In addition, organ failure has been shown to be a major determinant of duration of hospitalization for patients with acute pancreatitis.^[4,5,11] Singh et al^[5] reported that patients with BISAP score ≥3 developed organ failure much more frequently than those with BISAP score <3. In our study, BISAP score ≥2 had a high predictive value for organ failure, the predictive value of BISAP is much better than that of CTSI or Ranson score.

 

CRP, Hct and BMI are widely used independent prognostic factors for severe acute pancreatitis.^{[3, 12-17]} Serum CRP level serves as a nonspecific inflammation marker. A serum CRP level greater than 150 mg/L within 48 hours after the onset of symptoms is a proven predictor of severe acute pancreatitis.^{[13, 15]} In our study, however, CRP at presentation and after 48 hours had low predictive values for severe pancreatitis, necrosis, organ failure and death. There was no statistically significant difference between CRP at presentation and CRP after 48 hours with regard to predicting severity and death. Initial CRP was more accurate in predicting organ failure than it was after 48 hours. Interactions with CRP and other cytokines formed in the hepatocytes may have influenced these results. Several studies^[3,12,14] have suggested that hemoconcentration is an early predictor of pancreatic necrosis or organ failure.However, one study^[18] examining hemoconcentration in acute pancreatitis have failed to confirm this. We have shown that elevated, at admission and after 48 hours, had low predictive values for severe pancreatitis, organ failure, and death, but Hct had more predictive value for necrosis than CRP, BMI and even BISAP. Prior studies have reported that obesity, i.e., BMI ≥30, is an independent prognostic factor for poor outcome in patients with acute pancreatitis.^[16,17,19] However, obesity was not a powerful predictive factor for acute pancreatitis in our study. It may be that our sample reflected the relatively low prevalence of obesity in Asians compared with Caucasians. In any case, the remarkable finding was that BISAP had higher predictive value for severe pancreatitis, organ failure, and death than did CRP, Hct and BMI, which are routinely assessed, well-known prognostic factors. We propose that, compared with CRP, Hct and BMI, BISAP is superior in accuracy and accessibility as a prognostic factor for severe acute pancreatitis.

 

In summary, BISAP is as useful as APACHE-II and more useful than Ranson criteria, CTSI, CRP, Hct and BMI in predicting severity, organ failure, and death in patients with acute pancreatitis. BISAP scores are calculated from data that are clinically relevant and easy to obtain. The accuracy of BISAP in predicting organ failure is especially greater than its accuracy in predicting severe acute pancreatitis and death. Using BISAP score to identify patients at risk of organ failure within 24 hours of admission will help to guide decision-making of treatment and therefore, to improve patient outcomes.

 

 

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