Rapid Determination of Maintenance Heparin Infusion Rates with the Use of Non-Steady-State Heparin Concentrations

OBJECTIVE: To compare heparin dosage adjustment using only activated partial thromboplastin time (APTT) with a method using non-steady-state heparin concentrations (HCs) to rapidly achieve and maintain an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of therapy. DESIGN: Randomized, blind, parallel comparison of an empiric dosing method based only on APTT with a dosing method based on the calculation of heparin clearance using non-steady-state HCs. SETTING: A private community teaching hospital. The patient, physician, nurses, and investigators were blinded to the dosing method. Only the clinical staff pharmacist, who received the consult and made all dosage adjustments, was not blinded. PATIENTS: All patients requiring heparin for the treatment of thromboembolic disease were evaluated for potential inclusion in the study. Patients were enrolled in the study if they had a clinical diagnosis of deep venous thrombosis confirmed by objective means such as venography or ultrasonography. Patients were excluded if they had active bleeding, platelet dysfunction, thrombocytopenia, severe hepatic disease (total bilirubin >25.7 μmol/L), renal disease, or evidence of stroke. Patients were also excluded if they were receiving heparin prior to enrollment. MAIN OUTCOME MEASURE: Maintenance of an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of heparin therapy. RESULTS: Thirty-four patients were enrolled in the study; 17 in each group. The groups were not significantly different with regard to gender, age, baseline APTT, or mean loading dose (p>0.5). Mean initial infusion rates for the control and HC groups were 1042 ± 194 and 1071 ± 143 units/h, respectively (p>0.5). After the first rate adjustment at 4 hours, the difference achieved significance at 1032 ± 232 and 1367 ± 317 units/h for the control and HC groups, respectively (p<0.01). At 12 hours, 18.8 percent of the patients in the control group were subtherapeutic; by 24 hours, 33.3 percent were subtherapeutic. No patients became subtherapeutic in the HCs group during the first 24 hours. CONCLUSIONS: This study demonstrates that, in contrast to standard heparin dosing methods, the use of non-steady-state HCs allows patients with deep venous thrombosis to rapidly achieve and maintain therapeutic APTT ratios throughout the critical first 24 hours of therapy.