Low-Volume Continuous Hemodiafiltration With Nafamostat Mesilate Increases Trypsin Clearance Without Decreasing Plasma Trypsin Concentration in Severe Acute Pancreatitis

Abstract

Continuous hemodiafiltration (CHDF) has recently been used for treatment of severe acute pancreatitis. CHDF is capable of eliminating small molecules from blood, but whether trypsin can be eliminated by CHDF is not clear. In this study, elimination of trypsin-like enzyme activity (TLE) and cationic trypsin-like immunoreactivity (TLI) using low-volume CHDF was examined at the first CHDF session in eight patients with severe acute pancreatitis. CHDF was performed with a polysulfone hemofilter (membrane area, 0.7 m2) and nafamostat mesilate, a protease inhibitor and anticoagulant, at a blood flow rate of 100 ml/min and a filtration and dialysis flow rate of 10 ml/min each. Before beginning CHDF, plasma TLE was 3.41 +/- 2.86 nmol/(ml.min), and TLI was 5,900 +/- 9,008 ng/ml. The average plasma clearances of TLE and TLI achieved by the circuit during the 12-hour therapy were 56.7 +/- 4.9 ml/min and 8.0 +/- 7.2 ml/min, respectively. The average plasma clearance of TLI into the waste fluid was 2.4 +/- 1.6 ml/min whereas TLE was below the measurable sensitivity. The plasma concentration of TLE and TLI remained unchanged. These results indicate that low-volume CHDF using nafamostat mesilate as an anticoagulant can increase trypsin plasma clearance. However, low-volume CHDF is not effective to eliminate the plasma trypsin concentration.

Nafamostat Mesilate is not Appropriate as an Anticoagulant during Continuous Renal Replacement Therapy in Dogs

“…However, we suspect that NM or its metabolites stimulate the chemoreceptor trigger zone in the area postrema and cause vomiting, because we administered NM intravenously and subsequently observed acute onset of vomiting. CRRT has been utilized for patients with severe conditions such as acute pancreatitis, sepsis, and multiple organ failure [8,12,15]. Therefore, it is essential to avoid vomiting associated with NM because it can cause aspiration pneumonia and other deleterious effects.…”

Is Continuous Venovenous Hemofiltration Effective Against Severe Acute Pancreatitis?

“…Four comparative studies and seven case series were included . Two case series that analyzed the same populations were combined . The characteristics of the included studies are described in Table .…”

“…To interrupt the inflammatory cascade, continuous venovenous hemofiltration (CVVH) has been proposed to eliminate the excessive release of cytokines and the abnormal release of enzymes. Several studies have indicated that CVVH may be effective in treating SAP . CVVH has been correlated with decreased levels of serum cytokines , decreased serum levels, increased clearance rates of serum enzymes , decreased intra‐abdominal pressure (IAP), and even decreased mortality rates .…”

Early Continuous Veno-Venous Hemofiltration Is Effective in Decreasing Intra-Abdominal Pressure and Serum Interleukin-8 Level in Severe Acute Pancreatitis Patients with Abdominal Compartment Syndrome

“…Despite all these evidence-based advances in the evaluation and treatment of SAP patients with ACS, ACS remains a life-threatening complication. In previous studies [7,8], continuous veno-venous hemofiltration (CVVH) was found to efficiently remove various humoral mediators to prevent the deterioration of SIRS to the MODS in SAP, and have reported its efficacy in SAP patients [9,10]. But, there are a few reports regarding ACS therapy with CVVH.…”

“…The pathophysiology of ACS is considered to be directly associated with the pancreas inflammation, which initiates a cascade of acute peripancreatic fluid collections (APFC), capillary leakage syndrome (CLS), and paralytic ileus leading to an elevated IAP [4,5]. Several studies describing the effect of various interventions to lower IAP in SAP patients with both medical and surgical measures have been published in recent years [6,7]. Despite all these evidence-based advances in the evaluation and treatment of SAP patients with ACS, ACS remains a life-threatening complication.…”