Change in Heparin Potency and Effects on the Activated Clotting Time in Children Undergoing Cardiopulmonary Bypass

Abstract

Heparin is the anticoagulant most commonly used for cardiopulmonary bypass (CPB), and the activated clotting time (ACT) is its primary monitor. In October 2009, the Food and Drug Administration changed the United States Pharmacopeia (USP) monograph for unfractionated heparin to incorporate new quality tests and a new potency assay and reference standard. This latter change was anticipated by in vitro tests to reduce heparin potency by 10% in each USP unit dose. After integration of the "new" heparin into our practice, we subjectively noticed less prolongation of the ACT with our routine heparin bolus before the initiation of CPB. We performed this investigation to provide objective evidence of a reduction in the level of anticoagulation achieved with use of the new heparin as assessed by ACT values and to document the occurrence of having an ACT below our institutional threshold before the initiation of CPB. A retrospective chart review was performed on all children who underwent CPB at Children's Healthcare of Atlanta between July 1, 2008, and June 30, 2009, before the release of the new heparin ("old heparin" [OH] group) and between June 1, 2010, and May 31, 2011, after complete integration of the new heparin ("new heparin" [NH] group). Baseline ACTs and ACTs after the administration of 400 U/kg of heparin were recorded for both the OH and NH groups. We determined the number of patients in each group having an ACT <480 seconds after the initial heparin bolus but before the initiation of CPB. Additionally, patients were divided into 3 age groups (<1 month, 1 to 12 months, and >1 year) to analyze similar ACT changes. Postheparin ACTs were significantly lower in the NH group than in the OH group. There were significantly more patients having an ACT <480 seconds after the initial heparin bolus in the NH group (OH: 68 of 557 [12.2%] versus NH: 140 of 491 patients [28.5%]; P < 0.0001). The change remained significant when assessed across the age groups. In this investigation we provide objective evidence that the level of anticoagulation after the initial pre-CPB heparin bolus as assessed by the ACT is significantly less with use of the new heparin. This reduction remained consistent across 3 age groups and was associated with a more frequent occurrence of ACTs below our institutional threshold for the initiation of CPB. Consideration should be given to increasing the initial weight-based heparin dose administered before CPB.