Has the New USP Assay for Heparin Affected Dosage for Patients Undergoing Cardiopulmonary Bypass?

Abstract

In October 2009, the U.S. Pharmacopoeia (USP) changed the monograph for heparin to bring USP units in line with international units for heparin. The result was a 10% decrease in potency as measured by in vitro laboratory tests. This decrease led to questions regarding dosing guidelines. There existed a need for an in vivo study to determine the practical changes that may need to be implemented in regard to heparin administration for cardiopulmonary bypass in the clinical setting. A retrospective study was conducted to determine the heparin dose administered and the corresponding effect on patients undergoing coronary artery bypass grafting surgery using cardiopulmonary bypass. The study compared the heparin dose requirements and activated clotting time (ACT) results using the heparin before and after the USP changes. An analysis of the data was performed to determine the increased heparin dose required to achieve the same effect as before the USP change. This new heparin dosing protocol was instituted at Concord Hospital, Concord, NH. A prospective study was then preformed to verify the effects of the dosing change. In the new heparin group, the postheparin ACT fell by 9.1% (p = .028) and the patients achieving an ACT > 479 seconds fell by 12.8% as compared with the old heparin group. After adjustment of the loading dose calculation for heparin, the prospective study demonstrated the postheparin ACT (p = .684) and the percentage of patients achieving an ACT > 479 seconds (p = 1.000) to be similar to the values obtained before the USP change. An increase of the loading dose of approximately 12% is needed to achieve the patient effects seen before the UPS change.