Advancing the frontiers of clinical management in acute pancreatitis

Abstract

Acute pancreatitis has been known as a distinct clinical entity for more than a century, but the frontiers of its clinical management have not yet advanced enough to curb the high morbidity, mortality and cost of treatment in this disease. The management may principally be advanced either by detecting a specific therapeutic modality for acute pancreatitis or making better use of established non-specific modalities. This thesis aims to advance two frontiers of clinical management: classification of acute pancreatitis severity (which is an essential prerequisite for assessing the efficacy of a new therapeutic modality) and optimisation of enteral nutrition (the most promising non-specific modality in acute pancreatitis to date). Past severity classifications were based on empirical description of events deemed to be associated with severity. There has been little progress in regards to a sound scientific foundation on which to base classification of acute pancreatitis severity. In this thesis, the concept of causal inference is applied to classifying the severity of acute pancreatitis, and the best available evidence suggests that classification of severity should be based on local and systemic determinants. Local determinants relate to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. Systemic determinants relate to whether there is organ failure or not, and if present whether it is transient or persistent. Derivation of a classification based on available evidence for determinants of severity and the possibility of their interaction results in four categories of severity, i.e., 'mild', 'moderate', 'severe', and 'critical'. Enteral nutrition is a rapidly evolving frontier in the management of acute pancreatitis. This thesis demonstrates that enteral nutrition given via the nasogastric route is safe and well tolerated in most patients with acute pancreatitis. Further, when given within 24 hours of admission to patients with mild to moderate acute pancreatitis, it results in significantly reduced intensity and duration of initial abdominal pain, need for opiates, and risk of oral refeeding intolerance. Lastly, use of a relatively inexpensive polymeric formulation is as safe and effective as a more costly elemental formulation.