OF NORTH AMERICA
Risk and Markers of Severe Acute Pancreatitis
Georgios I. Papachristou, MDa,b,*, Gilles Clermont, MD, MScc, Arun Sharma, BAa, Dhiraj Yadav, MD, MPHa, David C. Whitcomb, MD, PhDa
Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA bDivision of Gastroenterology, Pittsburgh VA Health Care System, Pittsburgh, PA, USA c Center for Inﬂammation and Regenerative Modeling, CRISMA Laboratory and Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
cute pancreatitis (AP) is a common acute inﬂammatory process of the pancreas that affects approximately 100,000 individuals in theUnited States annually . The clinical course of AP varies signiﬁcantly between individuals. In most patients, the condition is mild and self-limiting, but approximately 20% of patients suffer severe attacks associated with prolonged hospitalization, signiﬁcant morbidity, and mortality ranging between 30% and 50% . The process is initiated by activation of pancreatic zymogens, resulting inpancreatic autodigestion and an inﬂammatory response mediated by the innate immune system. The inﬂammatory reaction is initiated at the site of injury and, if marked, can lead to systemic inﬂammation. The immune response is independent of the event or process that initiates activation of the digestive enzymes and pancreatic injury in AP, but accounts for much of the subsequent damage. Cytokines play acritical role in the pathogenesis of pancreatitis by driving the subsequent inﬂammatory response. Knowledge of the inﬂammatory cascade is important in recognizing when the peak response occurs for various cytokines and inﬂammatory mediators. A number of studies provide information of the proﬁle of inﬂammatory markers that peak on the day AP occurs, at 24 hours, 48 hours, and later. These studiesalso examine the potential of inﬂammatory markers to discriminate patients into high-risk and low-risk groups based on their physiologic measurements and clinical outcome. Early prognosis of severity in AP subjects remains unsatisfactory, however, and an extensive
*Corresponding author. GI Administration, Mezzanine Level 2, C Wing, UPMC Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA15213. E-mail address: papachristoug@ dom.pitt.edu (G.I. Papachristou).
0889-8553/07/$ – see front matter doi:10.1016/j.gtc.2007.03.003
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PAPACHRISTOU, CLERMONT, SHARMA, ET AL
search for objective tools that predict severity and outcome at the time of hospital admission remains a major challenge. MULTISYSTEM ORGANFAILURE AND PANCREATIC NECROSIS Eighty percent of patients with AP develop abdominal pain and elevated pancreatic enzyme levels in the blood and urine for a few days. Twenty percent of patients progress to a more severe course with a prolonged hospitalization or death. About 50% of deaths in subjects with severe AP occur within the ﬁrst week. An exaggerated inﬂammatory response and the resultantmultisystem organ failure are the primary causes of death when early mortality occurs . The ﬁrst sign of multisystem organ failure in AP subjects is commonly impaired lung function caused by adult respiratory distress syndrome. Systemic inﬂammation also affects the cardiovascular system, kidneys, and liver. Severe AP can be deﬁned in several ways. The Atlanta classiﬁcation system  deﬁnes severeAP based on organ dysfunction, including systolic blood pressure less than 90 mm Hg, PaO2 less than 60, serum creatinine greater than 2 mg/dL after rehydration, and gastrointestinal bleeding greater than 500 mL/24 hours. Furthermore, severe AP is deﬁned using the Ranson’s criteria with a score greater than or equal to 3  and the Acute Physiology and Chronic Health Evaluation (APACHE)-II...