Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery

Abstract

Objective Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. Methods This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. Results Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7–5.1 days) versus 4.2 days (2.9–5.2days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. Conclusions Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes.

Intraoperative tranexamic acid in pediatric bloodless cardiac surgery

“…In this study, we used a bolus of 100 mgÁkg À1 after induction of general anesthesia and before skin incision, followed by continuous infusion of 10 mgÁkg À1 Áh À1 intraoperatively, as advocated in previous reports. [6][7][8] TXA administration has generally not been associated with severe adverse events such as myocardial infarction, stroke, or renal failure. 17 We also experienced no postoperative neurological deficits, thromboembolic complications, or renal dysfunction in this study.…”

“…From January 2012, TXA was routinely given in bloodless cardiac surgery as a bolus of 100 mgÁkg À1 after induction of general anesthesia and before skin incision, followed by continuous infusion of 10 mgÁkg À1 Áh À1 intraoperatively, as advocated in previous reports. [6][7][8] The TXA group (n ¼ 31) included patients who underwent surgery with TXA (Transamin; Daiichi-Sankyo Co., Tokyo, Japan) between January 2012 and June 2013. The control group (n ¼ 40) included patients who underwent surgery without intraoperative TXA administration between January 2011 and December 2011.…”

Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: Results from a randomized trial

“…7-9 Glucocorticoid administration is among the most common methods to attenuate the clinical and biochemical features of the post-CPB inflammatory response, although the technique of steroid administration in neonatal cardiac surgery is highly variable. 8,9 To further confound matters, the limited number of studies investigating clinical outcomes associated with the use of corticosteroids in children requiring CPB yield contradictory results.…”

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

“…457 Aprotinin was used in >7000 patients, and compared with no antifibrinolytic therapy, aprotinin was associated with decreased bleeding and mortality without an increase in dialysis. In addition, in the recent report by Graham et al, 459 aprotinin was associated with reduced perioperative blood product use, improved early indexes of postoperative recovery, and attenuated indexes of cytokine activation. In 2007, the FDA limited the use of aprotinin to high-risk adult cardiac surgical patients.…”

“…458 An additional recent retrospective review compared 34 neonates who received aprotinin (before May 2008) and 42 neonates who received TXA (after May 2008). 459 Aprotinin was associated with reduced perioperative blood product use, improved early indexes of postoperative recovery, and attenuated indexes of cytokine activation.…”