Author Affiliations: Department of Intensive Care Unit (Huang J, Qu HP, Li L and Chen EZ); Department of Radiology (Zheng YF); Department of Surgery (Song XW and Xu ZW) and Department of Emergency (Mao EQ), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

Corresponding Author: En-Qiang Mao, MD, PhD, Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China (Tel/Fax: +86-21-64370045ext665528; Email: maoeq@yeah.net)

 

© 2016, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(15)60040-6

Published online December 30, 2015.

 

 

Contributors: HJ, QHP and CEZ proposed this study, drafted the paper, collected and analyzed the data. All authors contributed in design of the study, interpretation of data and drafting the final manuscript. HJ and CEZ contributed equally to this article. MEQ is the guarantor.

Funding: This project was supported by a grant from Shanghai Science and Technology Committee (12411950500).

Ethical approval: The study protocol was approved by the Institutional Review Board of Ruijin Hospital, Shanghai, China.

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.

 

 

BACKGROUND: The Atlanta criteria for acute pancreatitis (AP) has been revised recently. This study was to evaluate its practical value in classification of AP, the severity assessment and management.

 

METHODS: The clinical features, severity classification, outcome and risk factors for mortality of 3212 AP patients who had been admitted in Ruijin Hospital from 2004 to 2011 were analyzed based on the revised Atlanta criteria (RAC) and the original Atlanta criteria (OAC).

 

RESULTS: Compared to the OAC group, the incidence of severe acute pancreatitis (SAP) was decreased by approximately one half (13.9% vs 28.2%) in the RAC group. The RAC presented a lower sensitivity but higher specificity, and its predictive value for severity and poor outcome was higher than those of the OAC. The proportion of SAP diagnosis and ICU admission in the early phase in the RAC group was significantly lower than that in the OAC group (P<0.05). Based on the RAC, the risk factors for death among SAP patients were older age, high CT severity index (CTSI), renal failure, cardiovascular failure, acute necrotic collection and walled-off necrosis. Compared to the OAC, the acute physiology and chronic health evaluation II (APACHE II) score, Ranson score, idiopathic etiology, respiratory failure and laparotomy debridement were not risk factors of death in contrast to walled-off necrosis. Interestingly, hypertriglyceridemia-related SAP had good outcomes in both groups.

 

CONCLUSIONS: The RAC showed a higher predictive value for severity and poorer outcome than the OAC. However, the RAC resulted in fewer ICU admissions in the early phase due to its lower sensitivity for diagnosis of SAP. Among SAP cases, older age, high CTSI, renal and cardiovascular failure, complications of acute necrotic collection and walled-off necrosis were independent risk factors for mortality.

 

(Hepatobiliary Pancreat Dis Int 2016;15:310-315)

 

KEY WORDS: acute pancreatitis; Atlanta criteria; classification; outcome

Acute pancreatitis (AP) varies in clinical manifestations, etiologies, and severity. Upper abdominal pain, nausea and vomiting are typical symptoms at onset, with the spectrum of the disease ranging from a mild self-limiting to a severe complicated course with multiple organ dysfunction and death.^[1] The original Atlanta criteria (OAC) for AP classification and definition have been universally applied since 1992.^[2] This system aimed to gain uniformity in the assessment of clinical severity and various complications of AP. For the past 20 years, this was the only widely accepted classification system used by clinicians and radiologists. However, many clinicians noticed the limitation of OAC and they realized that the OAC needs to be revised.^[3-7] Questions were mainly focused on the nonconformity between the diagnostic criteria of severe acute pancreatitis (SAP) and real severity and outcome.^{[8, 9]} The revised Atlanta criteria-2012 (RAC) was published recently.^[10] The severity of AP was classified as mild (MAP), moderately severe (MSAP) or severe (SAP). Local complications were also defined as acute peripancreatic fluid collections (APFC), acute pancreatic and peripancreatic necrosis (ANC), pancreatic pseudocyst (PPC) and walled-off necrosis (WON). These revisions received favorable responses from clinicians and radiologists. However, further evaluation is still needed before it is universally accepted.

 

Here, we analyzed the etiologies, clinical features and outcomes of patients with first-attack AP using the RAC system. In addition, we also compared the advantages and disadvantages between the RAC and OAC system.

 

 

We retrospectively analyzed the data from 3212 patients with AP who had been admitted within 72 hours after onset of symptoms in Departments of Emergency, Gastroenterology, Surgery and Intensive Care Unit (ICU) in Ruijin Hospital (Shanghai, China) from January 2004 to December 2011. To ensure the inclusion of only eligible patients with first-attack of AP, patients with recurrent AP, chronic pancreatitis or pancreatic cancer were excluded. Patients with incomplete data (e.g., deceased within 24 hours after admission, missing Ranson scores, missing computed tomography (CT) diagnosis, or termination of treatment on halfway) were also excluded. Demographic and clinical characteristics of the patients were collected at the time of admission.

 

According to the RAC system, the diagnosis of AP requires two of these features: onset of upper abdominal pain, serum lipase or amylase level at least three times higher than the normal upper limit, diagnosed by imaging techniques such as contrast-enhanced CT, ultrasonography (US) and/or magnetic resonance imaging scan.^[10] Severity of AP was classified as MAP, MSAP or SAP in the RAC system. MAP is the most common form of AP which involves no organ failure, local or systemic complications and usually resolves in the first week. MSAP is defined as the presence of transient organ failure, local complications or exacerbation of co-morbid disease. SAP is defined as persistent organ failure (> 48 hours) affecting respiration, renal function or the cardiovascular system. Local complications were defined as APFC, ANC, PPC and WON. In the OAC system, the severity of AP was classified as MAP and SAP.^[2] The SAP diagnosis requires at least one of the following criteria: (a) APACHE II score ≥8; (b) Ranson score ≥3; (c) organ failure (i.e., transient and persistent); and (d) local complications (i.e., necrosis, abscess or pseudocyst).

 

The etiology was considered to be of biliary origin when biliary tract stones were detected by US, CT or magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or operation without other probable causes. Alcohol was considered to be an etiological factor if there was either consumption of more than 80 g/d for more than 5 years or presence of social or weekend abuse. For pancreatitis due to hypertriglyceridemia (HTG), a serum triglyceride (TG) level of more than 1000 mg/dL or 500-1000 mg/dL with a history of HTG was necessary, in addition to exclusion of other triggers.^{[2, 11, 12]} Lacking any of the above evidence or other direct causes, any unexplained pancreatitis was defined as idiopathic AP. Other etiologies, such as alcoholic, sphincter of Oddi dysfunction, pregnancy associated, iatrogenic injury, abdominal trauma, pancreatic duct obstruction, pancreas divisum, ampullary obstruction, hyper-calcemia, drugs related and autoimmune, were defined as “others” in this study.

 

SPSS 17.0 software (SPSS Inc., Chicago, IL, USA) was used for data analysis. The distributions of quantitative variables were tested. Normally and non-normally distributed quantitative variables were presented as the mean±standard deviation and mean, respectively. Continuous variables were compared between the groups using an unpaired t-test and a paired t-test within each group. Categorical variables were compared using the Chi-square test. For small samples, analysis of variance and Fisher’s exact test were used to analyze continuous and categorical variables as appropriate. Statistical significance was set at P<0.05.

 

 

A total of 3212 patients (1825 males and 1387 females) with first-attack AP were included in this study. The median age of the patients was 54 years (range 41-67). The causes of first-attack AP were biliary diseases (2012/3212, 62.6%), HTG (431/3212, 13.4%), idiopathic (393/3212, 12.2%) and others (376/3212, 11.7%). Overall, 1577 (49.1%) of these patients underwent operations, 1317 (41.0%) followed by ERCP/cholecystectomy and 267 (8.3%) by laparotomy debridement. One hundred and forty-nine (4.6%) patients were deceased. The average length of hospital stay was 24±19 days.

 

The variations of severity classification of AP were shown in Table 1. Compared to the OAC group, the incidence of SAP decreased by approximately one half (13.9% vs 28.2% ) in the RAC group. Additionally, the incidence of MAP decreased from 71.8% to 44.4%, and the new definition of MSAP showed an incidence of 41.8% in the RAC group.

 

Among 149 deaths, two were due to sudden cardiac arrest, one due to cerebral hemorrhage within 48 hours after disease onset, and the remaining 146 all had persistent organ failure. Thus, the 149 dead patients were classified as having SAP in the OAC group, and 146 in the RAC group. The predictive values of the two systems for prediction of mortality are shown in Table 2. Within the OAC system, APACHE II score ≥8, Ranson score ≥3 and organ failure had similar sensitivities, specificities and positive predictive values, while local complications had a much lower specificity (0.036) and a positive predictive value (0.167). And in the RAC system, persistent renal failure and cardiovascular failure had lower sensitivities (0.446 and 0.774, respectively) but higher specificities (0.756 and 0.793, respectively) and positive predictive values (0.482 and 0.646, respectively) than persistent respiratory failure (a sensitivity of 0.938, a specificity of 0.114 and a positive predictive value of 0.341). The negative predictive value of both of the systems ranged from 0.967 to 1.000.

 

The clinical features of SAP in the two groups were analyzed (Table 3). In the RAC group, APACHE II score, Ranson score, incidence of idiopathic etiology, laparotomy debridement, and duration of hospital stay were higher than those in the OAC group (P<0.05), whereas HTG-induced SAP was significantly decreased (P<0.05). There were no significant differences in age, gender, CTSI and biliary etiology between the two groups.

 

Patients with SAP usually need ICU observation and treatment. Their outcomes are affected by the severity and time of diagnosis. Of the deaths 42.3% (63/149) occurred in the early phase, and 57.7% (86/149) in the late phase. Among 906 patients with SAP in the OAC group, 73.3% were diagnosed and 68.3% were admitted into the ICU in the early phase (Table 4). The rates of later diagnosis and admission were 26.7% and 31.7%, respectively. Among 445 patients with SAP in the RAC group, 62.0% were diagnosed and 49.0% were admitted into ICU in the early phase, and the later diagnosis and admission rates were 38.0% and 51.0%, respectively. The rates of SAP diagnosis and ICU admission in the early phase showed a significant difference between the OAC and RAC groups (P<0.05).

 

We further analyzed the independent risk factors related to death in SAP patients (Table 5). In the OAC group, older age, high APACHE II score, Ranson score, CTSI, idiopathic etiology, organ failures (respiratory, renal and cardiovascular), ANC and laparotomy debridement were risk factors for death. In the RAC group, older age, high CTSI, organ failures (renal and cardiovascular), complications of ANC and WON were risk factors for death. Interestingly, an etiology of HTG was well correlated with good outcome in both groups, whereas complication of infected necrosis and laparotomy debridement showed negative relations to the poor outcome only in the RAC group.

 

 

The incidence of first-attack AP has large regional differences with rates ranging from 4 to 45 per 100 000 annually in the population.^[13-18] The cause of AP is predominantly associated with gallstones and alcohol consumption, the proportion of which varies in different countries and the geographical areas within a country.^[14] The epidemiological distribution of 3212 AP patients in this study was similar to the same regional reports.^[19-21]

 

The RAC system was considered to be superior to the OAC for severity estimates and outcome predictions. We found that RAC-directed classification of SAP decreased by approximately one-half, while case fatality doubled as compared to the OAC system. It is worth to mention that the persistent organ failures also reflected as higher APACHE II and Ranson scores, higher incidence of laparotomy debridement and longer hospital stay. Meanwhile, the persistent organ failures had higher specificities and positive predictive values in predicting mortality. Patients who developed persistent organ failure in early phase were at increased risk of death.^{[22, 23]}

 

It is important to identify patients with potentially SAP who require early aggressive treatment. Our data showed that 42.3% of the deaths happened in the early phase. Meanwhile, the SAP diagnosed according to the OAC and ICU admission rate were 73.3% and 68.3%, respectively, and both were significantly higher than those assessed by the RAC (62.0% and 49.0%, respectively). Thus, the advantage of the RAC is that the revised classification had a higher predictive value for severity and poor outcome. However, the disadvantage of the RAC is the lower sensitivity of SAP diagnosis, particularly in the early phase, which may cause fewer ICU admissions and more mortalities.

 

Most studies indicated a trend of decrease in mortality rates of AP over the decades, while high mortality (15%-36%) still existed in severe cases requiring intensive care.^{[1, 14, 24-26]} We further analyzed the risk factors of death in SAP patients. The data based on the RAC system showed that older age, high CTSI, organ failures (renal and cardiovascular), complications of ANC and WON were positively correlated to the poor outcomes. Compared to the OAC system, the variables such as APACHE II score, Ranson score, idiopathic etiology, respiratory failure and frequent laparotomy debridement were not risk factors of death, while WON was added in the risk factors of death in the RAC.

 

The increasing mortality was associated with increasing age in AP patients, which was also mentioned in the present study.^[14] The APACHE II and Ranson score systems were practical in the prediction of the severity of pancreatitis.^{[27, 28]} Here we demonstrated their sensitivities in the prediction of mortality, but their specificities and positive predictive values for mortality were far lower than persistent renal and cardiovascular failures. Persistent organ failure was a key factor in severity classification and outcome prediction.^{[16, 25]} We found that persistent renal and cardiovascular failures were good predictors of mortality with high specificities and positive predictive values. However, the persistent respiratory failure presented a much lower specificity and a positive predictive value, and there was no significant difference between the survival and nonsurvival groups. Its high incidence and frequent involvement in multiple organ failure might reduce its independent predictive value.^[29] Idiopathic pancreatitis is a special group with uncertain etiology, which might contribute to a high mortality.^[30] Its severity is related to multiple organ failures. The revised classification of SAP reduces its predictive value for mortality. The CTSI and local complications of ANC and WON focus on pancreatic and peripancreatic necrosis, which is consistent with the importance of revised definitions of local complications.

 

 Interestingly, the factors of HTG, infectious necrosis and laparotomy debridement have shown negative relations to the poor outcome. In our study, HTG-related AP often presented with APFC, intra-abdominal hypertension and respiratory failure, but fewer patients presented with pancreatic necrosis. Blood lipid adsorption and fluid resuscitation in the early phase could effectively alleviate these conditions and improve outcomes. Infectious necrosis was frequently seen in severe cases of the RAC system and it was not related to poor outcome. In addition, the operation itself was not relevant to the deterioration of the disease, and effective debridement was able to control infection, reduce organ failure, and improve the prognosis.

 

In conclusion, the RAC system uses easily identified clinical and radiologic criteria to unify the classification of AP and the definition of local complications, which hopefully facilitates treatment planning and improves outcomes. This retrospective study may help us to understand the advantages and disadvantages of the RAC. However, additional multicenter prospective studies are needed to further validate and improve this system.

 

 

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