One study suggests that 10% to 15% of patients receiving usual heparin doses for CPB will have detectable heparin levels 2 hours after prot- amine reversal [97]. Another study nds that detectable heparin levels, using both anti-Xa and viscoelastic mea- surements, are present immediately after, 2 hours after, and 4 hours after protamine administration [22]. Usual methods of monitoring heparin reversal and measuring postoperative coagulation (eg, ACT and acti- vated partial thromboplastin time) do not detect residual heparin levels [84, 98]. A randomized trial involving 300 patients showed that a continuous infusion of protamine after initial protamine reversal (25 mg/h for 6 hours) abolishes heparin rebound and results in modest, but signi cant, reductions in chest tube blood loss but not transfusion requirements [99]. Class I Recommendation  Complications associated with protamine reversal of heparin after CPB: For patients at high risk for anaphylactic response to protamine who have pul- monary hypertension and circulatory collapse shortly after protamine administration, discontinu- ation of protamine and implementation of resusci- tative measures including reinstitution of CPB with adequate anticoagulation may be lifesaving. (Level of Evidence C) As one might expect with any drug, there are side ef- fects and complications associated with the use of prot- amine to reverse the effects of heparin after CPB. A unique feature of these complications associated with CPB is that they occur at a crucial time of the operative procedure. Life-threatening complications associated with protamine include anaphylaxis, pulmonary edema, and pulmonary hypertension [100]. Life-threatening car- diovascular compromise after intravenous protamine can occur even in young infants [101]. These complications are associated with operative mortality and serious organ dysfunction [102, 103]. It is likely that protamine compli- cations are underreported [100, 104]. 