Treatment of Severe Acute Pancreatitis - Current Standards and Future Trends

Today, severe acute pancreatitis remains a therapeutic challenge. Although the treatment concepts have changed during the past decades, mortality remains high. Severe acute pancreatitis is defined as acute pancreatitis complicated by either local (pancreatic necrosis) or systemic (pulmonary, renal, or cardiocirculatory failure, systemic inflammatory response syndrome) complications.¹ This definition has been in use since the early 1990s. Since then, our understanding of the classification of severe acute pancreatitis has improved. It appears to be important to stress that, although the terms ‘necrotizing pancreatitis’ and ‘severe acute pancreatitis’ are still used as synonyms, there are cases of a severe attack of acute pancreatitis without the presence of pancreatic necrosis, but with life-threatening systemic organ failure. On the other hand, in some selected cases, the course of necrotising pancreatitis might be self-limiting and without systemic complications.

Prognosis of Severe Acute Pancreatitis
The overwhelming majority of deaths are observed in patients with necrotizing pancreatitis. Most of the fatalities occur during the latter phase of the disease and are attributed to septic complications. Major progress has been made in recognizing that enteric bacteria play an important role in the course and outcome of necrotizing pancreatitis.² When necrotic areas become infected by enteric germs, the prognosis of a patient deteriorates. Mortality rates in infected necrosis are reported to be between 15 and 25%. The rate of infected pancreatic necrosis correlates closely with the amount of necrotic parenchyma in the retroperitoneum and therefore patients with subtotal to total necrosis of the gland have the highest risk of experiencing a fatal course.³ In contrast, sterile pancreatic necrosis has a better prognosis with lower mortality rates (between 5 and 10%). As a consequence, the discrimination between sterile pancreatic necrosis and infected pancreatic necrosis is one of the main staging principles of the current treatment guidelines.⁴ Nevertheless, there are apparently special subgroups of patients experiencing a fulminant early course of the disease with severe and progressive systemic complications during the initial phase of acute pancreatitis without having a pancreatic septic focus. These subgroups have been described recently and are characterised by high mortality rates. These entities are currently referred to as early severe acute pancreatitis.⁵

Pharmacological Treatment
Acute pancreatitis is a disease with multiple pathophysiological mechanisms and many of them are still only poorly understood. Nevertheless, with the increasing knowledge about the pathophysiological mechanisms, there have been numerous experimental and clinical trials with drugs interfering in these pathways. Attempts to inhibit pancreatic exocrine secretion either with atropine, somatostatin, ocreotide, glucagon, or calcitonin have not proven to be successful. The use of antiproteases (aprotinin, gabexate-mesilate) failed to have beneficial effects as well. The understanding that neutrophil activation, accompanied by a systemic inflammatory response syndrome (SIRS), with activation of the inflammatory mediator cascade as a basic pathophysiological principle has led to alternative treatment strategies interrupting inflammatory mediator response. As platelet-activating factor (PAF) is regarded as a key cellular mediator involved in SIRS, PAF inhibition appeared to be a promising approach to ameliorate the course of acute pancreatitis. The first clinical studies with the PAF-antagonist lexipafant were promising; however, these favorable results could not be confirmed in a large, double-blind, randomized trial.⁶

Consequently, the current common therapies of severe acute pancreatitis are not specific to the pancreas but follow the rules of general intensive care treatment.⁷ Pain reduction, fluid resuscitation and treatment of pancreatitis-associated organ dysfunctions are the standards of pharmacological therapy of the disease.