Asian Cardiovasc Thorac Ann 2000;8:15-18
© 2000 Asia Publishing EXchange Pte Ltd
Dosage of Epsilon-Aminocaproic Acid to Reduce Postoperative Blood Loss
Sandeep Chauhan, MD,
Akshay Kumar Bisoi, MCh,
Beeraka Heramba Rao, MD,
M Sanjeeva Rao, MCh,
Nita Saxena, MD,
Panangipalli Venugopal, MCh
Department of Cardiothoracic and Vascular Surgery
Cardiothoracic Sciences Centre
All India Institute of Medical Sciences
New Delhi, India
|
|
For reprint information contact: Akshay Kumar Bisoi, MCh Tel: 91 11 686 4851 Fax: 91 11 686 2663 Department of Cardiothoracic and Vascular Surgery, Cardiothoracic Sciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
|
 |
Abstract
|
|---|
Postoperative blood loss, blood and blood-product requirements, and complications were compared for 3 commonly used doses of epsilon-aminocaproic acid in 150 patients undergoing first-time coronary artery bypass surgery. The patients were randomly assigned to one of 4 groups. Group 1 (n = 30) served as a control, group 2 (n = 30) received a single dose of 150 mg•kg–1 of epsilon-aminocaproic acid after anesthetic induction, group 3 (n = 30) received a loading dose of 150 mg•kg–1 followed by infusion of 1 g•h–1 for 6 hours, and group 4 (n = 60) received doses of 150 mg•kg–1 at induction, on bypass, and after protamine. No patients, including those who had endarterectomies, experienced any complications attributable to epsilon-aminocaproic acid administration. All patients who received epsilon-aminocaproic acid had significantly less bleeding compared to controls. Groups 3 and 4 had the least blood loss and packed-cell requirements.
|
Introduction
|
|---|
Epsilon-aminocaproic acid (EACA) has been shown to be effective in reducing blood loss after cardiac surgery in several studies.1–3 However, the doses of EACA used in these studies have varied widely. Daily and colleagues4 used 10 g of EACA before surgical incision, 10 g in the cardiopulmonary bypass (CPB) pump, and 10 g after protamine reversal of heparin. Hardy and colleagues5 gave a 15-g bolus over 20 minutes, followed by a l-g•h–1 infusion. Arom and Emery6 administered a 5-g bolus just before the patient was put on CPB and 0.03 µg•kg–1 desmopressin after CPB. Vander Salm and colleagues7 used a 5-g loading dose after coming off CPB but before protamine administration, followed by infusion of l g•h–1 for 6 hours. A single 15-g dose of EACA was given with tranexamic acid at anesthetic induction by Yau and colleagues.8 In order to compare the relative efficacy of various doses of EACA, 3 dosing regimens of EACA commonly used in patients undergoing primary coronary artery bypass grafting (CABG) were tested.
|
Patients and Methods
|
|---|
After approval by the Research Ethics Committee of the All India Institute of Medical Sciences, this prospective study was conducted on 150 consecutive adult patients scheduled for first-time CABG. Informed consent was obtained from all patients. Those undergoing reoperation, emergency surgery, or with known coagulation disorders were excluded from the study. Patients with hepatic or renal disease were also excluded. However, patients given preoperative aspirin or heparin infusions were included.
Anesthetic management and CPB was standardized throughout the study and all operations were performed by the same surgical team, ruling out differences in surgical technique as a cause of variations in blood loss post-operatively. Anesthesia was induced with diazepam, morphine, and thiopentone sodium, along with vecuronium for muscle relaxation, and supplemented with isoflurane in air and oxygen, if required. CPB was conducted in all patients using a membrane oxygenator (Maxima Plus; Medtronic, Anaheim, CA, USA) under moderate hypothermia (28°C). The bypass circuit was primed with Ringer's lactate solution 20 mL•kg–1, sodium bicarbonate 7.5% (w/v) 1 mL•kg–1, mannitol 20% (w/v) 0.5 g•kg–1, and heparin 100 IU•kg–1. The patients were randomly assigned to one of 4 groups. Group l (n = 30) received no EACA and acted as the control group. Group 2 (n = 30) received 150 mg•kg–1 of EACA as a single dose after induction of anesthesia. Group 3 (n = 30) received 150 mg•kg–1 of EACA on induction of anesthesia, followed by an infusion from the start of CPB of 1 g•kg–1•h–1 for 6 hours. Group 4 (n = 60) received a 150 mg•kg–1 dose after anesthetic induction, 150 mg•kg–1 during CPB, and 150 mg•kg–1 after protamine ad-ministration. Blood remaining in the CPB circuit was processed through a cell saver (Dideco, Mirandola, Italy) and returned to the patient. Time taken for chest closure (from protamine administration to sternal closure) was recorded in all patients as an indirect assessment of coagulation status.
Postoperatively, cumulative chest tube drainage was recorded at 6, 12, and 24 hours. Packed red blood cells were transfused if the hematocrit was less than 30%, fresh frozen plasma and platelet concentrate were transfused when indicated, at the discretion of the intensive care resident. Reexploration rates, perioperative myo-cardial infarction, and any renal or thrombotic compli-cations were noted.
Results were expressed as mean ± standard deviation and were assessed by analysis of variance, followed by Student-Newman-Keul multiple range tests. Values of p < 0.05 were considered significant.
|
Results
|
|---|
The 4 groups were comparable in respect of age, sex, weight, body surface area, number of grafts, number of patients receiving internal mammary artery grafts, and CPB time (Table 1
). Chest closure time after protamine administration was longest in group 1 compared to the 3 groups given EACA.
Postoperative data are shown in Table 2. Blood loss at 6 hours in group 1 was significantly greater than in the other groups. At 12 hours, mean cumulative blood loss in the control group was still significantly greater than in the 3 EACA groups. Total blood loss in group 1 at 24 hours was also significantly greater in than the other groups. Packed red blood cell use was greatest in group 1 but use of blood components (fresh frozen plasma and platelet concentrate) was not significantly different among the 4 groups. Reexploration rates were highest in group 1. A total of 15 endarterectomies were performed in the 120 patients given EACA. No patient had a perioperative myocardial infarction or evidence of graft occlusion on the basis of ST segment changes in the corresponding electrocardiographic leads. None of the 150 patients had any renal or other complications such as thrombotic events.
|
Discussion
|
|---|
The antifibrinolytic agents aprotinin, tranexamic acid, and EACA, have been used clinically to reduce fibrino-lysis-induced postoperative blood loss after cardiac surgery. Because of its low cost and efficacy, EACA is quite popular. It is a monocarboxylic acid, structurally related to lysine. EACA is a competitive inhibitor of plasminogen and plasmin that digest fibrin, so EACA inhibits fibrinolysis associated with CPB. Clinically significant effects are seen with a plasma EACA concentration of 130 µg•mL–1, which is produced by a dose of 100 mg•kg–1 given every 4 hours as the half-life is about 3 hours.9 A study by Elliot and colleagues10 showed plasma EACA values during CPB were consistently greater than in-vitro fibrinolysis-inhibiting levels of 130 µg•mL–1 (by a factor of at least 2) during a mean CPB time of 149 ± 50 minutes. They used an EACA dose of 150 mg•kg–1 at induction and an infusion of 30 mg•kg–1•h–1 for 4 hours on starting CPB.
Our study compared the effects of 3 commonly used doses of EACA and although plasma EACA levels were not assessed, the clinical results are self-evident. All 3 groups of patients given EACA had less blood loss at 24 hours compared to the control group. Blood loss in the group given a single dose of EACA was not as effectively reduced as in the group given a loading dose followed by infusion for 6 hours or in the group given 3 doses. This difference was obviously due to the reduction in plasma EACA levels once bypass was established, so although EACA decreased fibrinolysis and blood loss compared to the control group, it was not sustained for as long as in the groups given additional doses. There was no significant difference between the group given EACA as a loading dose followed by infusion and the group given 3 sequential doses, either in respect of cumulative blood loss or blood-product requirements. Although some concern has been expressed over the use of EACA in patients undergoing endarterectomy, with regard to the occurrence of myocardial infarction from graft occlusion in the endarterectomized vessels, this was not seen in the 15 patients with endarterectomies who received EACA.8
Reexploration rates in the EACA groups were lower than in the control group but not statistically significant. None of the patients had any complication attributable to EACA administration. It was concluded that EACA in any of the 3 dosing regimens studied reduced postoperative blood loss. However, significant reductions in blood require-ments were seen only when EACA was given as a loading dose followed by infusion or as 3 sequential doses, rather than as a single dose. There was no difference in blood loss or blood requirements when EACA was given either as a loading dose followed by 6-hour infusion or as 3 sequential doses, and no evidence that EACA was contraindicated in patients undergoing endarterectomy.
|
References
|
|---|
-
Jordan D, Delphine E, Rose E. Prophylactic
-aminocaproic acid (EACA) administration minimizes blood replacement therapy during cardiac surgery. Anesth Analg 1995;80:827–9.[Medline]
-
Del Rossi AJ, Cernaianu AC, Botros S. Prophylactic treatment of post perfusion bleeding using -aminocaproic acid. Chest 1989;96:27–32.[Abstract/Free Full Text]
-
Karski JM, Teasdale SJ, Norman PH, Caroll JA. Prevention of post bypass bleeding with tranexamic acid and aminocaproic acid. J Thorac Cardiovasc Anesth 1993; 7:431–5.
-
Daily PO, Lamphere JA, Dembitsky WP, Adamson RM, Dans NF. Effect of prophylactic epsilon aminocaproic acid on blood loss and transfusion requirements in patients undergoing first time coronary artery bypass grafting. J Thorac Cardiovasc Surg 1997;108:99–108.[Abstract/Free Full Text]
-
Hardy JF, Belisle S, Dupont C, Havel F, Robitaille D, Roy M, et al. Prophylactic tranexamic acid and E aminocaproic acid for primary myocardial revascularization. Ann Thorac Surg 1998;65:371–8.[Abstract/Free Full Text]
-
Arom KV, Emery RW. Decreased postoperative drainage with addition of -aminocaproic acid before cardio-pulmonary bypass. Ann Thorac Surg 1994;57:1108–13.[Abstract]
-
Vander Salm TJ, Ansell JE, Okike ON, Marcicano TH. The role of epsilon aminocaproic acid in reducing bleeding after cardiac operations: a double blind randomised study. J Thorac Cardiovasc Surg 1988;95:538–40.[Abstract]
-
Yau TM, Carson S, Weisel RD, Ivanof J. The effect of warm heart surgery on postoperative bleeding. J Thorac Cardiovasc Surg 1992;103:1155–63.[Abstract]
-
Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs 1985;29:236–61.[Medline]
-
Elliot BG, Jonathan GS, Canada AT, Ayuso L, Newman MF, Reves GJ, et al. -aminocaproic acid plasma levels during cardiopulmonary bypass. Anesth Analg 1997; 85:248–51.[Abstract]
TOP
Abstract
Introduction
