A Pilot Study Comparing Anti-Inflammatory Effects Of TXA Versus EACA In Pediatric Congenital Heart Surgery

Bleeding under cardiopulmonary bypass (CPB) is one of the most common complications in
patients undergoing pediatric cardiac surgery. The inflammatory response produced during and
after CPB is a factor that adds significantly to the morbidity after cardiac surgery. A
number of factors have been shown to be involved inducing the inflammatory response. These
include complement system activation3 and activation of inflammatory cytokines, especially
IL-1 IL-64, IL-8 and TNF alpha.

Tranexamic Acid (TXA) and Epsilon-Aminocaproic Acid (EACA) are lysine analogues frequently
used as anti-fibrinolytic agents in patients undergoing CPB. Many authors have highlighted
the role of TXA in reducing blood loss and blood transfusion during and after CPB. Role of
EACA and aprotinin in decreasing pro-inflammatory response during and after CPB has been
well documented in adult literature. Patients undergoing redo sternotomy have higher
inflammatory response as compared to patients undergoing first cardiac surgery. It has also
been shown that the TXA can reduce the inflammatory response after CPB by acting directly or
indirectly on the inflammatory cytokines.

There are no studies directly comparing the anti-inflammatory properties of EACA and TXA in
the pediatric population undergoing CPB. In our institution, EACA is used as the standard of
practice to reduce the blood loss during pediatric cardiac surgeries, but the investigators
have now started using TXA more recently.

The aim of this study is to compare the anti-inflammatory and anti-fibrinolytic properties
of these two anti-fibrinolytic agents in pediatric patients undergoing CBP for cardiac
surgery.

Hypothesis: Tranexamic acid (TXA) has better anti-inflammatory profile as compared to
€-Amino Caproic Acid (EACA) which may help in reducing blood loss, renal injury, hepatic
injury and blood transfusion during and after CPB

Specific Objectives: During redo sternotomy procedures there is significant
anti-inflammatory response which occurs and plays a role in increasing amount chest tube
output, blood loss, renal injury, hepatic injury and ultimately patient morbidity and/or
mortality. The proposed study will help to know if antifibrinolytic agents are beneficial in
reducing the anti-inflammatory response produced and which of the two drugs (EACA or TXA),
has a better anti-inflammatory profile when used in a similar setting for patients
undergoing pediatric cardiothoracic surgery.

Specific Aims:

Evaluate whether TXA or EACA can decrease inflammatory response produced during redo
sternotomy procedures in pediatric patients and which drug decreases the injury and/or
cardiac dysfunction more as reflected by fluid balances, inotropic support, diuretic
requirement, length of ventilator support, length of ICU stay, and length of hospital stay.

Inclusion Criteria:

- Patients undergoing pediatric cardiac surgery, with redo sternotomy needing
cardiopulmonary bypass

Exclusion Criteria:

- Patients undergoing Fontan or Glenn procedures

- Allergy to EACA or TXA

- Baseline coagulation profile abnormality * (The coagulation profile will be used as
an exclusion criteria, if results available. Occasionally the results of coagulation
profile may be unavailable prior to surgery due to a clotted sample. For such
patients, as per the current clinical practice, we would not be redrawing the lab
solely for a research purpose)

- Prothrombin time [PT] >50% of High Normal value

- Partial Thromboplastin Time [PTT] > 50% of High Normal value

- Platelets < 50,000/mm3

- International normalized ratio (INR) >2

- Acute or chronic renal failure (creatinine > 2x high normal for age)

- Chronic hepatopathy (any transaminase > 2x high normal for age)

- Use of immunosuppressant drugs (within last 1 month)

- History of seizures (currently on antiepileptic drugs for epilepsy or history of
seizure within last 6 months)