Is high-dose nafamostat mesilate effective for the prevention of post-ERCP pancreatitis, especially in high-risk patients?

Department of Internal Medicine, Pusan National University School of Medicine, Yangsan-si, Gyeongsangnam-do, South Korea.
Pancreas (Impact Factor: 3.01). 07/2011; 40(8):1215-9. DOI: 10.1097/MPA.0b013e31822116d5
Source: PubMed

ABSTRACT Infusion of the protease inhibitor nafamostat mesilate (20 mg) effectively prevents post-ERCP pancreatitis, but only in low-risk groups. This study was performed to evaluate the use of high-dose nafamostat mesilate (50 mg) for prevention of post-ERCP pancreatitis (PEP), especially in high-risk groups.
A total of 608 patients who underwent ERCP were included; 13 patients were excluded. Patients were divided into 3 groups: controls (group A), infusion with 20 mg of nafamostat mesilate (group B), or infusion with 50 mg of nafamostat mesilate (group C). The incidence of PEP was analyzed.
The overall incidence of acute pancreatitis was 7.4% (44/595). There was a significant difference in the incidence of PEP with or without nafamostat mesilate (13.0% vs 4.0% and 5.1%, respectively; P < 0.0001). Subgroup analysis showed that in low-risk patients, the rate of PEP was significantly different with nafamostat (11.9% vs 2.7% and 4.0%, respectively; P = 0.007). In high-risk patients, the rate of PEP was not significantly different among treatment groups (14.6% vs 5.9% vs 6.9%, respectively; P = 0.108).
Nafamostat mesilate prophylaxis (20 or 50 mg) is effective in preventing post-ERCP pancreatitis. However, the preventive effect of high-dose nafamostat mesilate (50 mg) is not significant in high-risk patients.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this prospective trial was to compare the effect of ulinastatin and nafamostat on the prophylaxis of post-ERCP complications. Methods A total of 159 patients who underwent ERCP were divided into ulinastatin (n = 53), nafamostat (n = 53) and control (n = 53) groups. Each patient received ulinastatin (150,000 units), nafamostat (20 mg), or placebo from 2 to 4 h before ERCP to 6–8 h after ERCP. The primary endpoint was the incidence of PEP, and the secondary endpoints were the incidence of post-ERCP hyperamylasemia, hyperlipasemia and abdominal pain. Results The overall incidence of PEP was 6.3% (10/159) and no significant differences were observed between ulinastatin and nafamostat groups in terms of the incidences of PEP (1.9% and 3.8%, P = 0.560), hyperamylasemia, hyperlipasemia, and abdominal pain, although these were significantly lower than those of the control group (P < 0.001). Conclusions There was no significant difference for preventing PEP between ulinastatin and nafamostat and both drugs were efficacious for preventing post-ERCP complications.
    Pancreatology 07/2014; · 2.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O-positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate-induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction.
    American Journal Of Pathology 06/2014; 184(6):1773-84. · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Data regarding the incidence, severity and mortality of post-ERCP pancreatitis (PEP) have largely come from retrospective observational studies as opposed to randomized control trials (RCTs) Aim: To determine the incidence, severity and mortality of PEP in consecutive and high risk patients based on a systemic review of the placebo arms of RCTs. Methods: The MEDLINE, EMBASE and Cochrane databases were searched from the inception of each database to June 2012 to identify RCTs evaluating the efficacy of drugs and pancreatic duct stents in preventing PEP. Only full text publications which reported the incidence of PEP were chosen for analysis. The incidence, severity and mortality of PEP from the placebo or no intervention arms of RCTs were extracted for consecutive and high risk patients to avoid the influence of an intervention on the development of PEP. The severity of PEP was defined according to the Cotton criteria. Results: There were a total of 101 RCTs with 12,921 patients in the placebo or no stent groups. The cumulative incidence of PEP was 9.5%. There were 54 RCTs with 8,791 patients which reported the severity of PEP, in which 5.8%, 3.3% and 0.7% of cases were mild, moderate and severe, respectively. The cumulative mortality was 0.18%. There were 20 RCTs with 2,216 patients at high risk of PEP. The cumulative incidence of PEP among high risk patients was 12.5%. The severity of PEP in high risk patients was classified as mild, moderate and severe in 7.9%, 3.9% and 0.9% respectively. The cumulative mortality among high risk patients was 0.17%. Among high risk patients, 27% of cases were performed for suspected sphincter of Oddi dysfunction (SOD) versus 15.7% in the total cohort. The incidence of PEP was 12.3% in North American centers compared to 8.7% in European or 8.3% in Asian centers. The proportion of ERCPs performed in North America for SOD was 38.2% compared to 6% in Europe and 2.5% in Asia. Conclusion: Based on the placebo arm of 101 RCTs evaluating pharmacologic agents and pancreatic stents for the prevention of PEP, the cumulative incidence of PEP was 9.5% with severe disease in 0.7% and 0.18% mortality. Among high risk patients, the cumulative incidence of PEP was 12.5% with severe disease in 0.9% and 0.17% mortality. The higher rates of PEP in North America versus Europe and Asia are likely due to higher proportion of ERCPs being performed for patients with suspected SOD. (Table presented).
    Gastrointestinal Endoscopy 05/2013; 77(5):AB392. · 4.90 Impact Factor