Combination therapy of continuous arterial infusion of nafamostat mesilate and arterial injection of human urinary trypsin inhibitor (ulinastatin) for severe acute pancreatitis

Background: We propose a treatment for severe acute pancreatitis that combines continuous arterial infusion (CAI) of nafamostat mesilate and arterial injection of the human urinary trypsin inhibitor, ulinastatin (UTI) to inhibit the activity of neutrophil elastase (PMN elastase) in the pancreas during the early stage of pancreatitis. The present study investigated effectiveness of this combination therapy in improving symptoms associated with pancreatitis. Methods: The diagnosis of severe acute pancreatitis followed the diagnostic criteria established by the Japanese Ministry of Health and Welfare in 1990. The present combination therapy was performed on a total of six patients with severe acute pancreatitis and shifts in the levels of different cytokines were measured. Results: The results showed that even a single injection of UTI administered during the placement of a continuous arterial infusion catheter was sufficient to eliminate pain. Shifts in the levels of different cytokines (PMN elastase, interleukin-6, and TNF α) were compared between patients with severe acute pancreatitis and the control group. No significant differences were observed in the pre-therapy levels of PMN elastase, interleukin-6 and TNFα between the two groups. However, after the start of therapy, the levels of these cytokines increased in some patients with severe pancreatitis. Conclusions: Our study suggests that the suppression of neutrophil activation in the pancreas by arterial injection of UTI during the early stage of pancreatitis is important in preventing its progression and the onset of multiple organ failure. And our study also suggests that the combination therapy must be applied to the treatment of severe pancreatitis.