CRRT, the continuous renal replacement therapy, is widely applied in the field of intensive
care medicine. This technology is known as an alternative therapy to save injured kidney with
advantages of the accurate volume control, stable acid-alkali electrolyte equilibrium
maintenance and hemodynamic stability.
Anticoagulation is an important part of this therapy. An ideal anticoagulant and a reasonable
anticoagulation process would help CRRT function well. Therefor an insufficient
anticoagulation would cause a poor curative effect of CRRT.
Heparins, reginal citrate anticoagulant (RCA) and anticoagulant-free are the most common
methods applied in CRRT. However, heparins would lead to hemorrhage and heparin-induced
thrombocytopenia (HIT). And RCA is the absolute contraindication of liver failure and shock
status, which would easily cause citrate accumulation and acidosis. While anticoagulant-free
method is often suitable for patients with acute hepatic failure, citrate metabolic disorder,
sever acidosis and coagulation dysfunction. According to aforementioned reasons, a new
effective anticoagulation of CRRT needs to be carried out.
Nafamostat Mesylate (NM) is a late-model anticoagulant. This serine protease inhibitor with
broad spectrum can inhibit kinds of enzymes on the process of coagulation. It has strong
inhibitory effects on thrombin, coagulation factors Ⅻ a, Xa, VIIa, kallikrein, fibrinolytic
enzyme, complement system C1r, C1s and trypsin. NM is mainly rapidly decomposed by
carboxylesterase in the liver and also removed by dialysis or filtration. The elimination
half life of is only 8 minutes. If NM is applied as a reginal anticoagulant, approximate 40%
NM is removed by dialysis and / or convection in cardiopulmonary bypass circuit, and then
rapidly degraded by esterase in liver and blood, which ensures security in patients with
bleeding tendency.
Based on the information above, the investigators designed an observational clinical study
aimed to testify that NM would have equivalent anticoagulant results compared with those
traditional ways and might even have a better effect than traditional anticoagulant therapy.
In this study, the average filter life-span will be calculated and compared in groups to
assess effectiveness of NM. And the safety of NM will be assessed by comparing the incidence
rate of the bleeding and/or massive hemorrhage between groups. Besides, the best dose of NM
will be titrated during the trial along with targeting a best monitoring value of NM.
Either in the observational or in the control group, the continuous renal replacement therapy
should be implemented as indications. The investigators need to record trial details into an
eCRF as protocol required. The details include main diagnosis, clinical status before first
CRRT, the primary indications for first CRRT, the coagulation function, laboratory indexes,
the frequency and site of hemorrhage, the incidence of hyper-coagulable state, the average
life-span of filters during first CRRT, the number of filters caused by clotting, and times
of transfusion.
The anticoagulation in observational arm will be implemented as follows.
Admixture: to fully dissolve 50mg NM into 5% glucose solution.
Pipeline pre-flushing: to dissolve 50mg NM into 1000ml 5% glucose solution. to prime the
filters and extracorporeal circuits with the mixtures above. Then to use 5% glucose
solution and 0.9% saline solution sequentially flushing the pipe-line and filters for a
complete elution and to ensure the drug residue would be as less as possible.
Drug infusion: The maintaining dose of NM is 10-20mg/hr.
Monitoring: APTT will be tested every 30min to 2h initially. The goal of APTT is settled
as 80s-100s in circuits and as 40s-50s in body. Once the steady state is reached, the
monitoring interval will be adjusted to 1224h. To reach the target monitoring goal, the
NM will be added or reduced by 24mg each time.
While in control group, the CRRT steps will be implemented by Standard operating procedures
for blood purification(version2021, China).
Data collection and safety: in this study, an independent offline eCRF will be applied in
collecting data. Specific staff will be trained to use eCRF correctly and collect data
regularly. The details are displayed in CRF.
