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Table of Contents
COMMENTARY  
Year : 2015  |  Volume : 18  |  Issue : 1  |  Page : 27-28
Comparison of tranexamic acid with aprotinin in pediatric cardiac surgery


Department of Cardiac Anaesthesia, Cardio Neuro Centre, AIIMS, New Delhi, India

Click here for correspondence address and email

Date of Web Publication1-Jan-2015
 

How to cite this article:
Chauhan S. Comparison of tranexamic acid with aprotinin in pediatric cardiac surgery. Ann Card Anaesth 2015;18:27-8

How to cite this URL:
Chauhan S. Comparison of tranexamic acid with aprotinin in pediatric cardiac surgery. Ann Card Anaesth [serial online] 2015 [cited 2019 Dec 15];18:27-8. Available from: http://www.annals.in/text.asp?2015/18/1/27/148317


Pediatric patients are at risk for bleeding after cardiac surgery on cardiopulmonary bypass (CPB), because of various factors such as a small blood volume compared to the CPB prime causing hemodilution, low levels of coagulation factors, and qualitative differences in fibrinogen and plasminogen. Congenital heart disease in addition is associated with platelet and coagulation abnormalities.

Use of lysine analogs such as epsilon amino caproic acid (EACA), tranexamic acid (TA) and aprotinin in children undergoing cardiac surgery on CPB have been well described, [1],[2],[3],[4],[5] however the data available is still far from complete.

Epsilon aamino caproic acid and TA are analogs of the amino acid lysine. They exert their antifibrinolytic effect by interfering with the binding of plasminogen to fibrin, which is necessary for activation of plasminogen to plasmin. Both EACA and TA have less anti-inflammatory properties than the aprotinin. TA is ten times more potent (and also ten times more expensive) than EACA. Comparable doses of both agents are used clinically. Aprotinin is a nonspecific serine protease inhibitor derived from bovine lung. It is a peptide that acts by inhibiting kallikrein and plasmin leading to inhibition of fibrinolysis and improving platelet preservation. Kallikrein is an enzyme involved in contact activation that accelerates activation of hemostatic, fibrinolytic and inflammatory systems during CPB. All the three antifibrinolytic agents are primarily excreted by the kidneys.

All the various studies on use of the three antifibrinolytic agents in pediatric cardiac surgery have left no doubt that all these three agents, reduce postoperative blood loss and transfusion requirements in the postoperative period, however the concerns with the use of these three agents are not related to bleeding, but to (1) dosing (2) side-effects (3) complications.

The main problem relating to the use of antifibrinolytics in children is the fact that there are very few studies if any which have studied the pharmacokinetics of these drugs in children. Most of the doses used (and there are as many doses as there are publications), are extrapolated from adult studies and have no basis on pharmacokinetics specially in neonates and children, where the volume of drug distribution and drug elimination may vary significantly in neonates, infants and older children compared with adults.

Chauhan et al. [1] compared 4 clinically published doses available in literature on TA and found a loading dose of 10 mg/kg, 10 mg/kg in prime and 10 mg/kg of TA after protamine reversal to be the best of the 4 doses they compared.

In the case of aprotinin, doses used must produce a plasma level of 250 KIU/ml is required for kallikrein inhibition and 125 KIU/ml to inhibit plasmin keeping in mind that the CPB in neonates and infants and children forms a large source of hemodilution and decrease in plasma antifibrinolytic levels. [6] If adequate CPB prime loading with the antifibrinolytic agent is not done to compensate for this large CPB prime volume and dosing is based only on the patient weight adequate plasma levels may not be achieved. Studies on safety have been lacking, with none of the large series reporting any adverse events, although theoretically micro vascular thrombosis, renal failure are possible. Stroke and convulsions have been reported especially with TA and anecdotal reports or case reports are available regarding these complications. Antifibrinolytics are helpful in reducing postoperative blood loss in children, but concerns of correct pharmacokinetic based dosing and possible side-effects, or complications remain.

 
   References Top

1.
Chauhan S, Bisoi A, Kumar N, Mittal D, Kale S, Kiran U, et al. Dose comparison of tranexamic acid in pediatric cardiac surgery. Asian Cardiovasc Thorac Ann 2004;12:121-4.  Back to cited text no. 1
    
2.
Chauhan S, Das SN, Bisoi A, Kale S, Kiran U. Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J Cardiothorac Vasc Anesth 2004;18:141-3.  Back to cited text no. 2
    
3.
Chauhan S, Kumar BA, Rao BH, Rao MS, Dubey B, Saxena N, et al. Efficacy of aprotinin, epsilon aminocaproic acid, or combination in cyanotic heart disease. Ann Thorac Surg 2000;70:1308-12.  Back to cited text no. 3
    
4.
Chauhan S, Bisoi A, Modi R, Gharde P, Rajesh MR. Tranexamic acid in paediatric cardiac surgery. Indian J Med Res 2003;118:86-9.  Back to cited text no. 4
    
5.
Chauhan S, Bisoi AK. EACA in pediatric cardiac surgery to decrease blood loss. Indian J Med Res 2000;111:57-61.  Back to cited text no. 5
    
6.
Beath SM, Nuttall GA, Fass DN, Oliver WC Jr, Ereth MH, Oyen LJ. Plasma aprotinin concentrations during cardiac surgery: Full-versus half-dose regimens. Anesth Analg 2000;91:257-64.  Back to cited text no. 6
    

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Correspondence Address:
Sandeep Chauhan
Department of Cardiac Anaesthesia, Cardio Neuro Centre, AIIMS, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.148317

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