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Item Characteristics and Operative Outcomes for Children Undergoing Repair of Truncus Arteriosus: A Contemporary Multicenter Analysis(Elsevier, 2019) Mastropietro, Christopher W.; Amula, Venu; Sassalos, Peter; Buckley, Jason R.; Smerling, Arthur J.; Iliopoulos, Illias; Riley, Christine M.; Jennings, Aimee; Cashen, Katherine; Narasimhulu, Sukumar Suguna; Gowda, Keshava Murty Narayana; Bakar, Adnan M.; Wilhelm, Michael; Badheka, Aditya; Moser, Elizabeth A. S.; Costello, John M.; Pediatrics, School of MedicineObjective We sought to describe characteristics and operative outcomes of children who underwent repair of truncus arteriosus and identify risk factors for the occurrence of major adverse cardiac events (MACE) in the immediate postoperative period in a contemporary multicenter cohort. Methods We conducted a retrospective review of children who underwent repair of truncus arteriosus between 2009 and 2016 at 15 centers within the United States. Patients with associated interrupted or obstructed aortic arch were excluded. MACE was defined as the need for postoperative extracorporeal membrane oxygenation (ECMO), cardiopulmonary resuscitation (CPR), or operative mortality. Risk factors for MACE were identified using multivariable logistic regression analysis and reported as odds ratios (OR) with 95% confidence intervals (CI). Results We reviewed 216 patients. MACE occurred in 44 patients (20%) and did not vary significantly over time. Twenty-two patients (10%) received postoperative ECMO, 26 (12%) received CPR, and 15 (7%) suffered operative mortality. With multivariable logistic regression analysis (which included adjustment for center effect), factors independently associated with MACE were failure to diagnose truncus arteriosus prior to discharge from the nursery (OR:3.1; 95%CI:1.3,7.4), cardiopulmonary bypass duration greater than 150 minutes (OR:3.5; 95%CI:1.5,8.5), and right ventricle-to-pulmonary artery conduit diameter greater than 50mm/m2 (OR:4.7; 95%CI:2.0,11.1). Conclusions In a contemporary multicenter analysis, 20% of children undergoing repair of truncus arteriosus experienced MACE. Early diagnosis, shorter duration of cardiopulmonary bypass, and use of smaller diameter right ventricle-to-pulmonary artery conduits represent potentially modifiable factors that could decrease morbidity and mortality in this fragile patient population.Item Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment(Wiley, 2015-07) Yang, Qi; Jerath, Angela; Bies, Robert R.; Wąsowicz, Marcin; Pang, K. Sandy; Department of Medicine, IU School of MedicineTranexamic acid (TXA), an effective anti-fibrinolytic agent that is cleared by glomerular filtration, is used widely for cardiopulmonary bypass (CPB) surgery. However, an effective dosing regimen has not been fully developed in patients with renal impairment. The aims of this study were to characterize the inter-patient variability associated with pharmacokinetic parameters and to recommend a new dosing adjustment based on the BART dosing regimen for CPB patients with chronic renal dysfunction (CRD). Recently published data on CPB patients with normal renal function (n = 15) were re-examined with a two-compartment model using the ADAPT5® and NONMEMVII® to identify covariates that explain inter-patient variability and to ascertain whether sampling strategies might affect parameter estimation. A series of simulations was performed to adjust the BART dosing regimen for CPB patients with renal impairment. Based on the two-compartmental model, the number of samples obtained after discontinuation of TXA infusion was found not to be critical in parameter estimation (p > 0.05). Both body weight and creatinine clearance were identified as significant covariates (p < 0.005). Simulations showed significantly higher than normal TXA concentrations in CRD patients who received the standard dosing regimen in the BART trial. Adjustment of the maintenance infusion rate based on the percent reduction in renal clearance resulted in predicted plasma TXA concentrations that were safe and therapeutic (~100 mg·L(-1) ). Our proposed dosing regimen, with consideration of renal function, is predicted to maintain effective target plasma concentrations below those associated with toxicity for patients with renal failure for CPB.