Comparison of Different Doses of  -Aminocaproic Acid in Children for Tetralogy of Fallot Surgery: Clinical Efficacy and Safety Anju Sarupria, DM, MD,* Neeti Makhija, MD,* Ramakrishnan Lakshmy, PhD,† and Usha Kiran, MD* Objective: The purpose of this study was to compare 2 different doses of -aminocaproic acid (EACA) and assess their relative efficacy and safety in children undergoing cor- rective surgery for tetralogy of Fallot (TOF). Design: A prospective, randomized, controlled study. Setting: A tertiary care center. Participants: One hundred twenty children undergoing corrective surgery for TOF using cardiopulmonary bypass (CPB). Interventions: Group 1 received 100 mg/kg of EACA after induction, upon initiation of CPB, and after protamine. Group 2 received 75 mg/kg of EACA after induction, fol- lowed by a maintenance infusion of 75 mg/kg/h until chest closure, and an additional 75 mg/kg upon initiation of CPB. Group 3 did not receive any antifibrinolytic agent or placebo. Measurement and Main Results: Cumulative mean blood loss, total packed red blood cells, and fresh frozen plasma requirements were significantly less in group 2 (p < 0.01). There were no significant differences in the total platelet concentrate transfused, re-exploration rate, incidence of re- nal failure, arrhythmias, neurologic complications, mortal- ity, or length of intensive care unit stay among the 3 groups. The incidences of perioperative ST/T changes and chest closure time were significantly less in group 1 and group 2 (p < 0.01). The duration of mechanical ventilation was sig- nificantly less in group 2 (p < 0.01). Conclusions: EACA was effective in reducing the postop- erative blood loss and transfusion requirements in children undergoing corrective cardiac surgery on CPB for TOF. The dose regimen of 75 mg/kg after induction, followed by a maintenance infusion of 75 mg/kg/h until chest closure, and an additional 75 mg/kg upon initiation of CPB were more effective. © 2012 Elsevier Inc. All rights reserved. KEY WORDS: -aminocaproic acid, tetralogy of Fallot, car- diopulmonary bypass C ARDIOVASCULAR SURGERY with cardiopulmonary bypass (CPB) activates coagulation, inflammation, and fibrinolysis, which may have deleterious effects on patient outcome. 1-3 Pediatric patients especially are at an increased risk for postoperative bleeding because of the immaturity of the hepatic and immune systems. 4-6 Children have a smaller blood volume compared with the prime in the CPB circuit, leading to hemodilution, which produces impaired hemostasis. 6 Children with congenital cyanotic heart disease (CCHD) also have qual- itative and quantitative abnormalities in coagulation proteins plasminogen and fibrinogen, 7 platelet abnormalities, 8-10 and enhanced fibrinolysis. 7,11-13 Various pharmacologic agents such as lysine analogs and aprotinin have been used to decrease perioperative bleeding. After the worldwide withdrawal of aprotinin (Bayer Healthcare Pharmaceuticals Communication, Leverkusen, CT), only lysine analogs, namely -aminocaproic acid (EACA) and tranexamic acid (TXA), remain available to reduce perioperative bleeding. A strong correlation exists between the perioperative use of TXA and the occurrence of seizures after cardiac surgery, 14-17 but no reports of such a potentially detrimental side effect could be found using EACA. In addition, the substantial difference in cost between EACA and the more expensive TXA led the authors to change their institutional blood-conservation protocol to EACA as their routine prophylactic antifibrinolytic therapy. There is a reasonable amount of literature examining the use of EACA 13,18 to reduce postoperative bleeding after congenital heart surgery. All these studies had large variability in patient population, procedures, methods, and dosing schemes with variable efficacy. Most of the dosing schemes used for EACA have been empiric and not based on sound pharmacologic principles. 19,20 Literature on the pediatric use of EACA is significantly less complete, and issues of efficacy, safety, and dosing persist. In view of the large variation in the dosage of EACA, the authors compared a commonly used dose 21,22 with a dose suggested by pharmacokinetic modeling. 23 A specific patient group of children undergoing corrective cardiac surgery for tetralogy of Fallot (TOF) on CPB was selected to avoid the effects of changing clinical practices, such as surgical tech- nique, perfusion, or anesthesia. This prospective controlled study was conducted to evaluate the efficacy and safety of EACA in a specific patient group and to define an effective dosing scheme. METHODS After approval from the institute’s ethics committee and informed consent from the parents of the children, this study was conducted over a 24-month period from September 2009 on 120 consecutive children weighing 5 to 20 kg and undergoing corrective surgery on CPB for TOF. Children with renal dysfunction, a previous neurologic event, or a congenital bleeding disorder were excluded from the study. Using a computer-generated randomization list, children were assigned to 1 of 3 groups (n = 40 in each group). Group 1 received 100 mg/kg of EACA soon after induction over 10 to 15 minutes, a 100-mg/kg bolus of EACA upon the initiation of CPB, and 100 mg/kg of EACA after protamine administration over 10 to 15 minutes. 21,22 Group 2 received 75 mg/kg of EACA soon after induction over 10 to 15 minutes followed by a maintenance infusion of EACA at 75 mg/kg/h until chest closure and an additional EACA dose of 75 mg/kg upon the initiation of CPB as suggested by Ririe et al. 23 Group 3 did not receive any antifibrinolytic agents or placebo. Anesthesiologists managing the case were not blinded to the dosing regimen. From the Departments of *Cardiac Anaesthesia and †Cardiac Bio- chemistry, Cardiothoracic Centre, All India Institute of Medical Sci- ences, New Delhi, India. Address reprint requests to Neeti Makhija, MD, Department of Cardiac Anaesthesia, Cardiothoracic Centre, All India Institute of Medical Sciences, Room 9, 7th Floor, Ansari, Nagar, New Delhi 110029, India. E-mail: neetimakhija@hotmail.com © 2012 Elsevier Inc. All rights reserved. 1053-0770/2701-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2012.07.001 23 Journal of Cardiothoracic and Vascular Anesthesia, Vol 27, No 1 (February), 2013: pp 23-29