Figure 50-33 A, The pioneering work of Bull and colleagues showing a dose-response curve wherein a patient's baseline activated coagulation time (ACT) is demonstrated at point A. Initial heparin dosing of 200 IU produced an ACT of greater than 350 seconds, and the dose-response curve was drawn with an intersection at 400 (A) and 480 seconds (B). From these intersects one can determine what further dose to administer to patients. Although this represents the classic method described by Bull and colleagues, few centers have the time or patience to wait for multiple doses of heparin to slowly creep up to the acceptable ACT for bypass. B, The right side of the illustration demonstrates the response of a population to a two-stage dosing planned to give an ACT of 480 seconds. Note some significant scatter around the 480-second number. (From Bull BS, Huse WM, Brauer FS, Korpman RA: Heparin therapy during extracorporeal circulation: II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 69:685–689, 1975.)