Efficacy of nafamostat mesilate as anticoagulation during cardiopulmonary bypass for early surgery in patients with active infective endocarditis complicated by stroke

Abstract

Background and aim of the study: Recent brain complications (e.g., bleeding or infarction) in patients with active infective endocarditis (AIE) are recognized as a contraindication for early surgery. Nafamostat mesilate (NM) is a synthetic protease-inhibiting agent that has not only potent inhibitory activity against coagulation factors (Xlla, Xa) but also an anti-inflammatory action. Herein is reported the authors' successful surgical experience using NM with low-dose heparinization in patients with AIE complicated by recent cerebral complications.

Methods: Twenty-eight patients (mean age 54.9 +/- 18.7 years) who had undergone surgery for AIE of the native valve (n = 21) or prosthetic valve (n = 7) were reviewed retrospectively. AIE was present in the aortic (n = 8), mitral (n = 16), aortic/mitral (n = 4) and tricuspid (n = 1) valves. Twenty-two of 28 patients had preoperative stroke, and six had active brain bleeding. Surgery was performed at a mean of 2.4 +/- 2.1 days after the onset of stroke. NM (209 +/- 152 mg) with low-dose heparin (3796 +/- 1218 IU; 67.4 +/- 20.3 IU/kg) was used for anticoagulation during cardiopulmonary bypass (CPB). The activated clotting time (ACT) was maintained at 350-450 s by the precise administration of NM into a cardiotomy reservoir (0.5 mg/kg/h) and a venous reservoir (sliding controlled dose at 1.5 mg/kg/h).

Results: The CPB time was 181.3 +/- 92.6 min. Five patients (17.8%) died during hospitalization due to persistent sepsis (n = 3), brain death caused by massive brain embolism before CPB establishment (n = 1), and pneumonia (n = 1). There was no further aggravation of intracranial bleeding, and no new hemorrhagic stroke.

Conclusion: Nafamostat mesilate, administered in conjunction with low-dose heparinization, served as an effective anticoagulant for early surgery in patients with AIE complicated by stroke, and caused no further deterioration of the cerebral lesions.