Lepirudin was initially used to manage CPB patients in the HAT studies (Riess et al., 1995, 1996) and has also been used successfully by other investigators for CPB (Warkentin and Greinacher, 2003). It is now accepted that lepirudin is a suitable alternative for anticoagulation during CPB in patients with acute HIT, provided that ECT monitoring is performed (Koster et al., 1998, 2000a,b; Johnston et al., 1999; Follis and Schmidt, 2000; Latham et al., 2000; Longrois et al., 2000). Neither the activated clotting time (ACT) nor the aPTT is appropriate for monitoring r-hirudin plasma levels in such high-dose situations (see Chapter 19).
Koster and colleagues (2000b) used lepirudin instead of heparin in 57 patients who had clinically diagnosed HIT and required CPB. The primary diagnoses included coronary artery disease (n = 27, including eight cases of MI), valvular heart disease (n = 14), combined coronary artery and valvular disease (n = 9), thoracic aortic aneurysms (n = 4), ventricular septal defect resulting from MI (n = 2), and atrial tumor (n = 1). In that study, anticoagulation was monitored with ECT, and lepirudin was maintained in the range of 3-4 mg/mL. The dose requirement for CPB was 0.016-0.035 mg/kg/min (1.0-2.1 mg/kg/h), with concurrent 24-h blood drainage of 50-2200 mL. Elimination of the drug at the conclusion of CPB was augmented through modified zero-balanced ultrafiltration and forced diuresis. However, drug removal was dependent on the prevailing renal function. Four patients with impaired renal function showed prolonged elimination and bleeding. Of the 57 patients, 54 achieved full recovery and showed no signs of thromboembolism over a 6-mo follow-up. Three patient deaths were unrelated to perioperative management.
For patients undergoing vascular surgery, the dosage of lepirudin should be adjusted for the risk for reocclusion (Hach-Wunderle, 2001). In patients with a low risk of reocclusion (e.g., in the aortic, iliac, and carotid arteries), a bolus of 0.4 mg/ kg (reduced in case of renal insufficiency) is given just before the vessel is clamped and is followed postoperatively by either an aPTT-adjusted infusion starting at 0.1 mg/kg/h or 15 mg injected sc b.i.d. (assuming normal renal function). In patients with an increased risk for reocclusion (e.g., undergoing calf-vessel reconstruction or bypass), a preoperative bolus of lepirudin (0.4 mg/kg [less in case of renal impairment]) should be administered, followed by a postoperative infusion of 0.1 mg/kg/h, aPTT-adjusted, for at least 3-4 days. For intraoperative flushing of the vessel during vascular surgery, up to 250 mL (0.1 mg/mL solution) of lepirudin can be used. As patients with acute HIT are at high risk for new TECs, therapeutic levels of anticoagulation should be achieved before surgery and maintained after surgery, at least until platelet counts are normalized.
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