title: Efficacy of nafamostat mesilate as anticoagulation during cardiopulmonary bypass for early surgery in patients with active infective endocarditis complicated by stroke.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Toshihito
authors: T
authors: Sakamoto
authors: Hiroya
authors: H
authors: Kano
authors: Shunsuke
authors: S
authors: Miyahara
authors: Takeshi
authors: T
authors: Inoue
authors: Naoto
authors: N
authors: Izawa
authors: Yasuko
authors: Y
authors: Gotake
authors: Masamichi
authors: M
authors: Matsumori
authors: Kenji
authors: K
authors: Okada
authors: Yutaka
authors: Y
authors: Okita
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001550:Benzamidines; D001780:Blood Coagulation Tests; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000379:methods; D002315:Cardiopulmonary Bypass / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004696:Endocarditis / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000601:surgery; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D020300:Intracranial Hemorrhages / Q000000981:diagnostic imaging / Q000209:etiology / Q000401:mortality; D007431:Intraoperative Complications / Q000517:prevention & control*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care / Q000379:methods; D011859:Radiography; D012189:Retrospective Studies; D020379:Risk Adjustment; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D001550:Benzamidines; D006146:Guanidines; C032855:nafamostat