Journal of Gastroenterology and Hepatology (1992) I, 363-366
ALIMENTARY T R A C T A N D PANCREAS
C-reactive protein and lactate dehydrogenase isoenzymes in the assessment of the prognosis of acute pancreatitis C - C . C H E N , S - S . W A N G , Y. C H A O , C-W. L U , S-D. L E E , Y - T . T S A I A N D K-J. LO
Division of Gastroenterology, Department of Medicine, Veterans General Hospital & National Yang-Ming Medical College Taipei, Taiwan
Abstract The value of serum C-reactive protein, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate in predicting the outcome of acute pancreatitis was evaluated for 57 episodes in 54 patients. Serum C-reactive protein levels on day 2, 4 and 7 after admission were significantly higher in 19 episodes of severe attacks than in 38 episodes of mild attacks (13.71 k 9.68, 9.00 k 7.54, 6.02 k 3.83 zrs 4.78 f 3.91, 3.30 k 3.61, 1.43 f 2.08 mg/dL; P < 0.0001, P < 0.005, P < 0.0001, respectively). The sensitivity, specificity and accuracy of predicting a severe attack were 94, 76 and 82% using C-reactive protein 2 8 mg/dL on day 2; 67, 92 and 84% using C-reactive protein 2 5 mg/dL on day 7; and 59, 76 and 70% using Ranson’s criteria 2 3. Increases in LDH-4 and LDH-5 isoenzymes were found in both groups, with LDH-4 being slightly higher in severe attacks than in mild attacks. There was no significant difference of erythrocyte sedimentation rate between both groups. When compared with Ranson’s criteria, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate, C-reactive protein is more valuable in the early assessment of the severity of acute pancreatitis. Key words: acute pancreatitis, C-reactive protein, L D H isoenzymes, Ranson’s criteria.
INTRODUCTION
METHODS
Between June and December 1990, 54 consecutive Acute pancreatitis varies from a mild, spontaneously patients with 57 attacks (two episodes in three patients) of healing condition to a severe disease leading to death. acute pancreatitis admitted to the Gastroenterology SecAlthough Ranson’s scoring system has been widely used, tion of Veterans General Hospital, Taipei were included there is no single indicator to predict the outcome of in this study. T h e diagnosis of acute pancreatitis was acute pancreatitis.’ The serum level of C-reactive protein based on serum amylase levels in excess of 450 U/L (CRP), an acute phase reactant, is elevated in many acute (mean + 10 s.d. the author’s institution) combined with inflammatory disorders,2 including acute p a n ~ r e a t i t i s . ~ - ~ abdominal pain. 12,1 Abdominal disorders with similar A serum CRP above 10mg/dL has been reported to clinical manifestations including perforated peptic ulcer, predict a severe attack of acute pan~reatitis,~-”although intestinal obstruction and abdominal malignancy were its usefulness is debated.*-” Lactate dehydrogenase excluded. Patients with hyperlipidaemia and turbid (LDH) is one of the eleven criteria of Ranson’s scoring serum were excluded because of possible errors in the system. There are five isoenzymes of LDH, and estimameasurement of CRP. Serum CRP was measured on the tion of isoenzymes may aid in the differential diagnosis of morning of day 2, 4 and 7 after admission with a myocardial infarction and acute pancreatitis. l 1 However, commercial kit by Behring Nephelometer-Ana1y~er.I~ there is no reference in the medical literature about LDH LDH isoenzymes and ESR were checked on day 2. LDH isoenzymes in acute pancreatitis. Erythrocyte sedimentaisoenzymes were determined by electrophoresis and ESR tion rate (ESR) is found to be elevated in many inflammawas measured by the Wintrobe method. Data were tory diseases. The present study was prospectively collected on admission and 48 h later to calculate the conducted to assess the relative value of serum CRP, score of Ranson’s criteria. Abdominal ultrasonography LDH isoenzymes, ESR and Ranson’s scoring system at was performed within 4 days after admission in every case. Computerized tomography scan of the abdomen was the early stage of acute pancreatitis in identifying patients done within 1 week in 28 patients when pancreatic likely to develop complications. Correspondence: Sun-Sang Wang, M.D., Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, 1121 7, R.O.C. Accepted for publication 31 March 1992.
C-C. Chen et al.
364 collection was suspected by ultrasonography or when gas blockade interfered with the examination. Three patients underwent laparotomy due to a deteriorating clinical course with necrotizing pancreatitis or pancreatic abscess. For the purposes of this study, a severe attack was defined as one that was complicated by: (i) pancreatic collection (pseudocyst, phlegmon or abscess); (ii) a systemic complication (acute respiratory insufficiency, renal failure, left ventricular failure, septicaemia); or (iii) death. l 5 All results are expressed as mean f s.d. MannWhitney U test was used to calculate the statistical significance. T h e correlation between serum CRP levels and Ranson's score was evaluated by linear regression analysis.
RESULTS Forty men and 14 women with a mean age 60.0 years (range 28-86 years) were studied. Nineteen patients (33%) developed a significant complication (including three pancreatic pseudocyst, eight phlegmon, four abscess, three systemic complications and one death) and were classified as severe, while 38 (67%) recovered without complications and were classified as having had mild attacks. T h e clinical characteristics of these patients are shown in Table 1. The serum CRP levels on day 2,4 and 7 after admission were 13.71 & 9.68,9.00 & 7.54, 6.02 k 3.83 mg/dL in severe attacks, significantly higher than the figures of 4.78 k 3.91, 3.30 +- 3.61, 1.43 f 2.08 mg/dL in mild attacks (P< 0.0001, P < 0.005, P < 0.0001, respectively; Fig. 1). To predict a severe attack, a cut-off value of CRP 2 8 mg/dL on day 2 gave a sensitivity of 94%, a specificity of 76% and an accuracy of 82%, and CRP 2 5 mg/dL on day 7 gave 67% sensitivity, 92% specificity and 84% accuracy. The sensitivity, specificity and accuracy were 42, 89 and 74% respectively, using the cut-off level of CRP on day 2 2 10 mg/dL (Table 2). Serum CRP was higher on day 2 than on day 4 in all but three patients. The mean duration of abdominal pain from the onset to admission was 1.4 days. The score of Ranson's criteria was 3.7 f 2.3 mg/dL in the severe group and 1.7 & 1.5 mg/dL in the mild group (P< 0.0005).T h e correlation coefficient between CRP and Ranson's score was 0.433 (P< 0.001).Those with a Table 1 Characteristics of patients with acute pancreatitis
Men : Women Mean age (years)
Aetiology Gallstone Alcohol
Post-ERCP* Unknown
Severe
Mild
(n = 19)
(n = 38)
Total (n = 57)
14: 5 59.9
2 8 : 10 60.1
42 : 15 60.0
11 4 1 3
24 4
35 8
3
4
7
10
* ERCP: endoscopic retrograde cholangiopancreatography.
I
2
7
4
Days
Figure 1 Sequential serum C-reactive protein levels in severe (W)and mild (0) pancreatitis. Results are expressed as mean t s.e.m. Dotted line represents the upper limit of normal range. Day 2: P < 0.0001; day 4: P < 0.005;day 7: P < 0.0001. Table 2 Comparison of C-reactive protein and Ranson's criteria for early prediction of severe pancreatitis
Cut-off Sensitivity Specificity Accuracy value
C-reactive protein (mg/dL) Day 2 2 8 Day 2 2 10 Day 7 2 5 Ranson's score 2 3
(YO)
(ON
94 42 67 59
76 89 92 76
("0)
82 74 84 70
score of 3 or more had significantly higher levels of CRP than those with a score less than 3 on day 2 (12.57f 11.45 vs 5.66 f 4.36mg/dL; P < 0.005)and on day 7 (3.99rt 3.21 ws 2.01 f 3.27mg/dL; P < 0.005).With a cut-off score 2 3, the sensitivity, specificity and accuracy were 59, 76 and 70% respectively. The serum C R P also had a higher prognostic sensitivity and accuracy in those with only gallstone-related pancreatitis (Table 3). The results of serum LDH and its isoenzyme profiles based on 42 patients (14severe and 28 mild attacks) are shown in Table 4.Serum LDH activity was significantly higher in severe attacks than in mild attacks (476 f 285 vs 287 f 206 U/L; P < 0.0005).Increase of the distribu-
Table 3 Comparison of C-reactive protein and Ranson's criteria in gallstone-related pancreatitis Cut-off Sensitivity Specificity Accuracy value (YO) ("0)
C-reactive protein (mg/dL) Day 2 2 8 Day 7 2.5 Kanson's score
2 3
100 71 56
74 89 74
81 84 69
CRP in acute pancreatitis
365
Table 4 LDH and its isoenzyme profiles in 14 severe and 28 mild attacks of acute pancreatitis Severity of acute pancreatitis
Severe Mild Normal Range*
LDH (U/L)
476 k 285* 287 t 206* 95-2 13
Isoenzyme distribution (YO) LDH-3 LDH-4
LDH-1
LDH-2
17.0 f 4.8 19.1 f 3.8 19-31
25.7 f 4.7 27.1 f 3.7 30-39
19.0 f 3.1 19.5 f 2.5 17-27
14.6 k 2.5t 13.2 f 2.2+ 5-13
LDH-5 23.6 f 8.0 21.7 f 7.0 5-12
* P < 0.0005 P < 0.05
* Data obtained in our institution Data expressed as mean f s.d. LDH: lactate dehydrogenase.
tion of LDH-4 and LDH-5 isoenzymes was found in both groups, but only- LDH-4 was found to have significant difference between severe and mild attacks (14.6 k 2.5 vs 13.2 k 2.2%; P < 0.05). With the cut-off value of LDH4 2 14%, the sensitivity, specificity and accuracy were 64, 7 1 and 69%. There was no significant difference of serum amylase (2204 k 1806 vs 2057 + 1257U/L) or ESR 31.5 f 17.4 vs 40.6 k 68.5 mm/h) between severe and mild attacks.
DISCUSSION Early prediction of the severity of acute pancreatitis may be important for adequate treatment. Although Ranson’s scoring system has been widely applied, its complexity limits its use in clinical practice. Other biochemical indicators, such as, CRP, phospholipase A,, and antiproteases have been proposed in recent year^.^-" In the present study, CRP done on day 2 or day 4 was confirmed to be a useful predictor of complications in acute pancreatitis. Mayer et al. reported that the risk of developing pancreatic collections is high when the CRP values remain high (210 mg/dL) at the end of the first week of i l l n e ~ s .Puolakkainen ~ et al. demonstrated that CRP > 14mg/dL on the second day after admission is significantly higher in patients with haemorrhagic pancreatitis than in those with mild attack^.^ Wilson et al. found that peak CRP (on day 2, 3 or 4) 2 21 mg/dL provides the best discrimination of complicated attacks with 83% sensitivity and 85% specificity.6 Buchler et al. reported that CRP is 95% predictive of pancreatic necrosis with a level greater than 10 mg/dL. For the best discrimination, the cut-off level of CRP on day 2 was 8 mg/dL. The reason why the cut-off value in this study was lower than other series is unknown, but variation in the definition of severe pancreatitis may contribute to this difference. The CRP level reached its peak around the second to fourth day of the i l l n e ~ s . ~T~h ~e mean , ~ ~ ’duration ~ of abdominal pain before admission was 1.4 days in this series. Thus the CRP levels on day 2 after admission were near the peak levels. The CRP value on day 7 was also useful in monitoring the clinical course. The fall of CRP level towards normal was delayed in severe cases in this series, as previously r e p ~ r t e d . ~ , ~ , ~ . ’ ~
Most previous reports on the application of serum CRP in acute pancreatitis have related mainly to patients with alcoholic p a n ~ r e a t i t i s . ~ ~Serum ~ . ’ . ~ CRP also gave a good prognostic value in gallstone-related pancreatitis in the current series. Whether serum CRP can be used as an indicator of surgery is c o n t r ~ v e r s i a l . ~ ”In ” ~ this study, only three patients with severe attacks underwent laparotomy. So the usefulness of serum CRP as an indicator of surgery could not be confirmed. A high level of serum L D H reflects non-specific tissue or organ darnage.l8 Alterations in serum L D H isoenzyme pattern can pinpoint the site of pathological involvement.” There has been no previous report documenting pattern change of LDH isoenzymes in acute pancreatitis. This study found that the percentage of LDH-4 and LDH-5 was higher than normal in acute pancreatitis. Only LDH-4 isoenzyme was significantly higher in severe attacks than in mild attacks. Because the predominant LDH isoenzymes in the pancreas are LDH-2 and LDH3,18 this implies that the pancreas is not the major origin of the increase of LDH. Damage to the liver, skeletal muscle or lung in severe attacks may contribute to the higher LDH level.” With the cut-off level of 14%, it was found that the prognostic value of LDH-4 was not as good as CRP in this study. In contrast to CRP, ESR or serum amylase failed to discriminate severe attacks from mild attacks. In summary, serum CRP as a single parameter can be used to predict the development of complications in acute pancreatitis. It is more useful in this respect than Ranson’s criteria, serum L D H isoenzymes or ESR. A high CRP level calls for an intensive search for pancreatic collection or other complications especially in those with mild initial clinical course.
REFERENCES 1. RANSONJ. H. C., RIFKINDK. M., ROSESD. F., et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg. Gynecol. Obstet. 1974; 139: 69-81. 2. PEPYSM. B. C-reactive protein fifty years on. Lancet 1981; i: 653-7. 3. MAYER A. D., MCMAHON M. J., BOWENM. et al. C-reactive protein: an aid to assessment and monitoring of acute pancreatitis. J. Clin. Pathol. 1984; 37: 207-1 1.
366
C-C. Chen et al.
4. PUOLAKKAINEN P., VALTONENV., PAANANEN A. et al.
C-reactive protein and serum phospholipase A, in the assessment of the severity of acute pancreatitis. Gut 1987; 28: 764-71. 5. PUOLAKKAINEN P. A. Early assessment of acute pancreatitis a comparative study of computed tomography and laboratory tests. Acra Chir. Scand. 1989; 155: 25-30. 6. WILSONC., HEADSA., SHENKIN A. et al. C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis. Br. 3. Surg. 1989; 76: 177-81. 7. BUCHLER M., MALFERTHEINER P., SCHOETENSACK C., UHLW. & BEGERH. G. Sensitivity of antiproteases, complement
infarct, thromboembolism of the pulmonary artery and acute pancreatitis. Kardiologiia 1975; 15 85-90. 12. WANGS. S., LINX. Z., TSAI Y. T. et al. Objective prognostic criteria of acute pancreatitis. Chin. 3. Gasrroenterol. 1987; 4: 63-7. 13. LIN X. Z., WANGS. S., TSAIY. T. et al. Serum amylase,
isoamylase and lipase in the acute abdomen. Their diagnostic value for acute pancreatitis. 3. Clin. Gastroenterol. 1989; 11: 47-52. A., PERKOM. & GRONROOS P. Rapid quantita14. HARMOINEN tive determination of C-reactive protein using LKB 8600 reaction rate analyzer. Clin. Chim. Acta 1981; 111: 117-20. 15. WILSONC., HEATHD. I. & IMRIEC. W. Prediction of
fac.ors and C-reactive protein in detecting pancreatic necrosis. Result of a prospective clinical study. Int. 3. Pancrearol. 1986; 1: 227-35.
8. FERGUSON C. M. & BRADLEY E. L. Can markers for pancreatic necrosis be used as indicators for surgery? Am. 3. G r g . 1990; 160: 459-61. 9. GUDGEON A. M., HEATHD. I., HURLEY P. et al. Trypsinogen activation peptides assay in the early prediction of severity of acute pancreatitis. Lancet 1990; 335: 4-8. 10. GROSSV., SCHOLMERICH J., LESERH. G. er al. Granulocyte elastase in assessment of severity of acute pancreatitis. Dig. Dis. Sci. 1990; 35: 97-105. G. G. Importance of determination 11. BARTB. I. & SEROCHKIN of the activity of lactate dehydrogenase and its isoenzymes in blood serum for differential diagnosis of myocardial
16.
17.
18. 19.
outcome in acute pancreatitis: a comparative study of APACHE 11, clinical assessment and multiple factor scoring systems. Br. J. Surg. 1990; 77: 1260-4. WANGS. S., LINX. Z., TSAI Y. T. et al. Clinical significance of ultrasonography, computed tomography and biochemical tests in the rapid diagnosis of gallstone- related pancreatitis: a prospective study. Pancreas 1988; 2: 153-8. TEERENHOVI O., NORDBACK I. C-reactive protein and pancreatic necrosis in acute necrotising pancreatitis. Ann. Chir. Gynaecol. 1988; 77: 61-3. MAEKAWA M. Lactate dehydrogenase isoenzymes. 3. Chromarogr. 1988; 429: 373-98. CHANCJ. S. & CHENG. H. Creatine kinase as a prognostic parameter in acute pancreatitis. Chin. J. Gasrroenterol. 1988; 5: 86-93.
ALIMENTARY T R A C T A N D PANCREAS
C-reactive protein and lactate dehydrogenase isoenzymes in the assessment of the prognosis of acute pancreatitis C - C . C H E N , S - S . W A N G , Y. C H A O , C-W. L U , S-D. L E E , Y - T . T S A I A N D K-J. LO
Division of Gastroenterology, Department of Medicine, Veterans General Hospital & National Yang-Ming Medical College Taipei, Taiwan
Abstract The value of serum C-reactive protein, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate in predicting the outcome of acute pancreatitis was evaluated for 57 episodes in 54 patients. Serum C-reactive protein levels on day 2, 4 and 7 after admission were significantly higher in 19 episodes of severe attacks than in 38 episodes of mild attacks (13.71 k 9.68, 9.00 k 7.54, 6.02 k 3.83 zrs 4.78 f 3.91, 3.30 k 3.61, 1.43 f 2.08 mg/dL; P < 0.0001, P < 0.005, P < 0.0001, respectively). The sensitivity, specificity and accuracy of predicting a severe attack were 94, 76 and 82% using C-reactive protein 2 8 mg/dL on day 2; 67, 92 and 84% using C-reactive protein 2 5 mg/dL on day 7; and 59, 76 and 70% using Ranson’s criteria 2 3. Increases in LDH-4 and LDH-5 isoenzymes were found in both groups, with LDH-4 being slightly higher in severe attacks than in mild attacks. There was no significant difference of erythrocyte sedimentation rate between both groups. When compared with Ranson’s criteria, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate, C-reactive protein is more valuable in the early assessment of the severity of acute pancreatitis. Key words: acute pancreatitis, C-reactive protein, L D H isoenzymes, Ranson’s criteria.
INTRODUCTION
METHODS
Between June and December 1990, 54 consecutive Acute pancreatitis varies from a mild, spontaneously patients with 57 attacks (two episodes in three patients) of healing condition to a severe disease leading to death. acute pancreatitis admitted to the Gastroenterology SecAlthough Ranson’s scoring system has been widely used, tion of Veterans General Hospital, Taipei were included there is no single indicator to predict the outcome of in this study. T h e diagnosis of acute pancreatitis was acute pancreatitis.’ The serum level of C-reactive protein based on serum amylase levels in excess of 450 U/L (CRP), an acute phase reactant, is elevated in many acute (mean + 10 s.d. the author’s institution) combined with inflammatory disorders,2 including acute p a n ~ r e a t i t i s . ~ - ~ abdominal pain. 12,1 Abdominal disorders with similar A serum CRP above 10mg/dL has been reported to clinical manifestations including perforated peptic ulcer, predict a severe attack of acute pan~reatitis,~-”although intestinal obstruction and abdominal malignancy were its usefulness is debated.*-” Lactate dehydrogenase excluded. Patients with hyperlipidaemia and turbid (LDH) is one of the eleven criteria of Ranson’s scoring serum were excluded because of possible errors in the system. There are five isoenzymes of LDH, and estimameasurement of CRP. Serum CRP was measured on the tion of isoenzymes may aid in the differential diagnosis of morning of day 2, 4 and 7 after admission with a myocardial infarction and acute pancreatitis. l 1 However, commercial kit by Behring Nephelometer-Ana1y~er.I~ there is no reference in the medical literature about LDH LDH isoenzymes and ESR were checked on day 2. LDH isoenzymes in acute pancreatitis. Erythrocyte sedimentaisoenzymes were determined by electrophoresis and ESR tion rate (ESR) is found to be elevated in many inflammawas measured by the Wintrobe method. Data were tory diseases. The present study was prospectively collected on admission and 48 h later to calculate the conducted to assess the relative value of serum CRP, score of Ranson’s criteria. Abdominal ultrasonography LDH isoenzymes, ESR and Ranson’s scoring system at was performed within 4 days after admission in every case. Computerized tomography scan of the abdomen was the early stage of acute pancreatitis in identifying patients done within 1 week in 28 patients when pancreatic likely to develop complications. Correspondence: Sun-Sang Wang, M.D., Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, 1121 7, R.O.C. Accepted for publication 31 March 1992.
C-C. Chen et al.
364 collection was suspected by ultrasonography or when gas blockade interfered with the examination. Three patients underwent laparotomy due to a deteriorating clinical course with necrotizing pancreatitis or pancreatic abscess. For the purposes of this study, a severe attack was defined as one that was complicated by: (i) pancreatic collection (pseudocyst, phlegmon or abscess); (ii) a systemic complication (acute respiratory insufficiency, renal failure, left ventricular failure, septicaemia); or (iii) death. l 5 All results are expressed as mean f s.d. MannWhitney U test was used to calculate the statistical significance. T h e correlation between serum CRP levels and Ranson's score was evaluated by linear regression analysis.
RESULTS Forty men and 14 women with a mean age 60.0 years (range 28-86 years) were studied. Nineteen patients (33%) developed a significant complication (including three pancreatic pseudocyst, eight phlegmon, four abscess, three systemic complications and one death) and were classified as severe, while 38 (67%) recovered without complications and were classified as having had mild attacks. T h e clinical characteristics of these patients are shown in Table 1. The serum CRP levels on day 2,4 and 7 after admission were 13.71 & 9.68,9.00 & 7.54, 6.02 k 3.83 mg/dL in severe attacks, significantly higher than the figures of 4.78 k 3.91, 3.30 +- 3.61, 1.43 f 2.08 mg/dL in mild attacks (P< 0.0001, P < 0.005, P < 0.0001, respectively; Fig. 1). To predict a severe attack, a cut-off value of CRP 2 8 mg/dL on day 2 gave a sensitivity of 94%, a specificity of 76% and an accuracy of 82%, and CRP 2 5 mg/dL on day 7 gave 67% sensitivity, 92% specificity and 84% accuracy. The sensitivity, specificity and accuracy were 42, 89 and 74% respectively, using the cut-off level of CRP on day 2 2 10 mg/dL (Table 2). Serum CRP was higher on day 2 than on day 4 in all but three patients. The mean duration of abdominal pain from the onset to admission was 1.4 days. The score of Ranson's criteria was 3.7 f 2.3 mg/dL in the severe group and 1.7 & 1.5 mg/dL in the mild group (P< 0.0005).T h e correlation coefficient between CRP and Ranson's score was 0.433 (P< 0.001).Those with a Table 1 Characteristics of patients with acute pancreatitis
Men : Women Mean age (years)
Aetiology Gallstone Alcohol
Post-ERCP* Unknown
Severe
Mild
(n = 19)
(n = 38)
Total (n = 57)
14: 5 59.9
2 8 : 10 60.1
42 : 15 60.0
11 4 1 3
24 4
35 8
3
4
7
10
* ERCP: endoscopic retrograde cholangiopancreatography.
I
2
7
4
Days
Figure 1 Sequential serum C-reactive protein levels in severe (W)and mild (0) pancreatitis. Results are expressed as mean t s.e.m. Dotted line represents the upper limit of normal range. Day 2: P < 0.0001; day 4: P < 0.005;day 7: P < 0.0001. Table 2 Comparison of C-reactive protein and Ranson's criteria for early prediction of severe pancreatitis
Cut-off Sensitivity Specificity Accuracy value
C-reactive protein (mg/dL) Day 2 2 8 Day 2 2 10 Day 7 2 5 Ranson's score 2 3
(YO)
(ON
94 42 67 59
76 89 92 76
("0)
82 74 84 70
score of 3 or more had significantly higher levels of CRP than those with a score less than 3 on day 2 (12.57f 11.45 vs 5.66 f 4.36mg/dL; P < 0.005)and on day 7 (3.99rt 3.21 ws 2.01 f 3.27mg/dL; P < 0.005).With a cut-off score 2 3, the sensitivity, specificity and accuracy were 59, 76 and 70% respectively. The serum C R P also had a higher prognostic sensitivity and accuracy in those with only gallstone-related pancreatitis (Table 3). The results of serum LDH and its isoenzyme profiles based on 42 patients (14severe and 28 mild attacks) are shown in Table 4.Serum LDH activity was significantly higher in severe attacks than in mild attacks (476 f 285 vs 287 f 206 U/L; P < 0.0005).Increase of the distribu-
Table 3 Comparison of C-reactive protein and Ranson's criteria in gallstone-related pancreatitis Cut-off Sensitivity Specificity Accuracy value (YO) ("0)
C-reactive protein (mg/dL) Day 2 2 8 Day 7 2.5 Kanson's score
2 3
100 71 56
74 89 74
81 84 69
CRP in acute pancreatitis
365
Table 4 LDH and its isoenzyme profiles in 14 severe and 28 mild attacks of acute pancreatitis Severity of acute pancreatitis
Severe Mild Normal Range*
LDH (U/L)
476 k 285* 287 t 206* 95-2 13
Isoenzyme distribution (YO) LDH-3 LDH-4
LDH-1
LDH-2
17.0 f 4.8 19.1 f 3.8 19-31
25.7 f 4.7 27.1 f 3.7 30-39
19.0 f 3.1 19.5 f 2.5 17-27
14.6 k 2.5t 13.2 f 2.2+ 5-13
LDH-5 23.6 f 8.0 21.7 f 7.0 5-12
* P < 0.0005 P < 0.05
* Data obtained in our institution Data expressed as mean f s.d. LDH: lactate dehydrogenase.
tion of LDH-4 and LDH-5 isoenzymes was found in both groups, but only- LDH-4 was found to have significant difference between severe and mild attacks (14.6 k 2.5 vs 13.2 k 2.2%; P < 0.05). With the cut-off value of LDH4 2 14%, the sensitivity, specificity and accuracy were 64, 7 1 and 69%. There was no significant difference of serum amylase (2204 k 1806 vs 2057 + 1257U/L) or ESR 31.5 f 17.4 vs 40.6 k 68.5 mm/h) between severe and mild attacks.
DISCUSSION Early prediction of the severity of acute pancreatitis may be important for adequate treatment. Although Ranson’s scoring system has been widely applied, its complexity limits its use in clinical practice. Other biochemical indicators, such as, CRP, phospholipase A,, and antiproteases have been proposed in recent year^.^-" In the present study, CRP done on day 2 or day 4 was confirmed to be a useful predictor of complications in acute pancreatitis. Mayer et al. reported that the risk of developing pancreatic collections is high when the CRP values remain high (210 mg/dL) at the end of the first week of i l l n e ~ s .Puolakkainen ~ et al. demonstrated that CRP > 14mg/dL on the second day after admission is significantly higher in patients with haemorrhagic pancreatitis than in those with mild attack^.^ Wilson et al. found that peak CRP (on day 2, 3 or 4) 2 21 mg/dL provides the best discrimination of complicated attacks with 83% sensitivity and 85% specificity.6 Buchler et al. reported that CRP is 95% predictive of pancreatic necrosis with a level greater than 10 mg/dL. For the best discrimination, the cut-off level of CRP on day 2 was 8 mg/dL. The reason why the cut-off value in this study was lower than other series is unknown, but variation in the definition of severe pancreatitis may contribute to this difference. The CRP level reached its peak around the second to fourth day of the i l l n e ~ s . ~T~h ~e mean , ~ ~ ’duration ~ of abdominal pain before admission was 1.4 days in this series. Thus the CRP levels on day 2 after admission were near the peak levels. The CRP value on day 7 was also useful in monitoring the clinical course. The fall of CRP level towards normal was delayed in severe cases in this series, as previously r e p ~ r t e d . ~ , ~ , ~ . ’ ~
Most previous reports on the application of serum CRP in acute pancreatitis have related mainly to patients with alcoholic p a n ~ r e a t i t i s . ~ ~Serum ~ . ’ . ~ CRP also gave a good prognostic value in gallstone-related pancreatitis in the current series. Whether serum CRP can be used as an indicator of surgery is c o n t r ~ v e r s i a l . ~ ”In ” ~ this study, only three patients with severe attacks underwent laparotomy. So the usefulness of serum CRP as an indicator of surgery could not be confirmed. A high level of serum L D H reflects non-specific tissue or organ darnage.l8 Alterations in serum L D H isoenzyme pattern can pinpoint the site of pathological involvement.” There has been no previous report documenting pattern change of LDH isoenzymes in acute pancreatitis. This study found that the percentage of LDH-4 and LDH-5 was higher than normal in acute pancreatitis. Only LDH-4 isoenzyme was significantly higher in severe attacks than in mild attacks. Because the predominant LDH isoenzymes in the pancreas are LDH-2 and LDH3,18 this implies that the pancreas is not the major origin of the increase of LDH. Damage to the liver, skeletal muscle or lung in severe attacks may contribute to the higher LDH level.” With the cut-off level of 14%, it was found that the prognostic value of LDH-4 was not as good as CRP in this study. In contrast to CRP, ESR or serum amylase failed to discriminate severe attacks from mild attacks. In summary, serum CRP as a single parameter can be used to predict the development of complications in acute pancreatitis. It is more useful in this respect than Ranson’s criteria, serum L D H isoenzymes or ESR. A high CRP level calls for an intensive search for pancreatic collection or other complications especially in those with mild initial clinical course.
REFERENCES 1. RANSONJ. H. C., RIFKINDK. M., ROSESD. F., et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg. Gynecol. Obstet. 1974; 139: 69-81. 2. PEPYSM. B. C-reactive protein fifty years on. Lancet 1981; i: 653-7. 3. MAYER A. D., MCMAHON M. J., BOWENM. et al. C-reactive protein: an aid to assessment and monitoring of acute pancreatitis. J. Clin. Pathol. 1984; 37: 207-1 1.
366
C-C. Chen et al.
4. PUOLAKKAINEN P., VALTONENV., PAANANEN A. et al.
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