Nafamostat Mesilate, As a Treatment for Heparin Resistance, Is not Associated with Perioperative Ischemic Stroke in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

OBJECTIVE:

Nafamostat mesilate, a short-acting protease inhibitor, treats heparin resistance during cardiopulmonary bypass. This study tested whether nafamostat mesilate is associated with perioperative ischemic stroke.

DESIGN:

A retrospective observational study.

PARTICIPANTS:

A total of 870 adult cardiac surgery patients.

INTERVENTION:

The authors retrospectively identified the patients who received nafamostat mesilate and who suffered symptomatic ischemic stroke within 30 postoperative days.

MEASUREMENTS AND MAIN RESULTS:

The authors evaluated perioperative patient characteristics in association with perioperative ischemic stroke and death. The patients were identified as heparin resistant if they had an activated coagulation time of <480 seconds after the administration of heparin at 400 to 500 U/kg. Heparin-resistant patients received a 10- to 20-mg bolus plus 25 to 50 mg/h of nafamostat mesilate and heparin at 100 U/kg intravenously every 1.5 to 2.0 hours to maintain an activated coagulation time over 480 seconds. Of the 870 patients, 11 (1.3%) suffered a perioperative ischemic stroke. Of the 190 (21.8%) patients who received nafamostat mesilate, 1 (0.5%) suffered ischemic stroke compared with 10 (1.5%) in 680 patients without nafamostat mesilate (Fisher exact test; p = 0.47; regression analysis; odds ratio, 0.35; 95% confidence interval, 0.45-2.8; p = 0.32); 3 (1.6%) patients with nafamostat mesilate died postoperatively within 30 days compared with 11 (1.6%) without nafamostat mesilate (Fisher exact test; p > 0.99, regression analysis; odds ratio, 0.98; 95% confidence interval, 0.27-3.5; p = 0.97).

CONCLUSIONS:

No evidence was found that nafamostat mesilate was associated with perioperative ischemic stroke in heparin-resistant patients undergoing cardiac surgery with cardiopulmonary bypass.