Bret A. Mettler

Acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass.

Objective: Hemolysis, occurring during cardiopulmonary bypass, is associated with lipid peroxidation and postoperative acute kidney injury. Acetaminophen inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced acute kidney injury. This pilot study tests the hypothesis that acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass. Design: Single-center prospective randomized double-blinded study. Setting: University-affiliated pediatric hospital. Patients: Thirty children undergoing elective surgical correction of a congenital heart defect. Interventions: Patients were randomized to acetaminophen (OFIRMEV [acetaminophen] injection; Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for four doses starting before the onset of cardiopulmonary bypass. Measurement and Main Results: Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes), and acute kidney injury were measured throughout the perioperative period. Cardiopulmonary bypass was associated with a significant increase in free hemoglobin (from a prebypass level of 9.8 ± 6.2 mg/dL to a peak of 201.5 ± 42.6 mg/dL postbypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. Acetaminophen attenuated the increase in plasma isofurans compared with placebo (p = 0.02 for effect of study drug). There was no significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers of lipid peroxidation. Acetaminophen did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin, or prevalence of acute kidney injury. Conclusion: Cardiopulmonary bypass in children is associated with hemolysis and lipid peroxidation. Acetaminophen attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients undergoing cardiopulmonary bypass.

Identifying Predictors of Hospital Readmission Following Congenital Heart Surgery through Analysis of a Multiinstitutional Administrative Database

BACKGROUND Despite resource burdens associated with hospital readmission, there remains little multiinstitutional data available to identify children at risk for readmission following congenital heart surgery. METHODS AND RESULTS Children undergoing congenital heart surgery and discharged home between January of 2011 and December 2012 were identified within the Pediatric Health Information System database, a multiinstitutional collection of clinical and administrative data. Patient discharges were assigned to derivation and validation cohorts for the purposes of predictive model design, with 17 871 discharges meeting inclusion criteria. Readmission within 30 days was noted following 956 (11%) of discharges within the derivation cohort (n = 9104), with a median time to readmission of 9 days (interquartile range [IQR] 5-18 days). Readmissions resulted in a rehospitalization length of stay of 4 days (IQR 2-8 days) and were associated with an intensive care unit (ICU) admission in 36% of cases. Independent perioperative predictors of readmission included Risk Adjustment in Congenital Heart Surgery score of 6 (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.8-3.7, P < .001) and ICU length of stay of at least 7 days (OR 1.9 95% CI 1.6-2.2, P < .001). Demographic predictors included Hispanic ethnicity (OR 1.2, 95% CI 1.1-1.4, P = .014) and government payor status (OR 1.2, 95% CI 1.1-1.4, P = .007). Predictive model performance was modest among validation cohort (c statistic 0.68, 95% CI 0.66-0.69, P < .001). CONCLUSIONS Readmissions following congenital heart surgery are common and associated with significant resource consumption. While we describe independent predictors that may identify patients at risk for readmission prior to hospital discharge, there likely remains other unreported factors that may contribute to readmission following congenital heart surgery.

Three-Region Perfusion Strategy for Aortic Arch Reconstruction in the Norwood

We describe a new method of selective regional perfusion during arch reconstruction in the Norwood procedure. The strategy involves direct sequential perfusion of the coronary and splanchnic circulations coupled with continuous cerebral perfusion, while repairing the arch in a distal to proximal fashion. This technique provides the potential for decreased coronary and splanchnic ischemic times, which in combination with continuous selective cerebral perfusion may further allow for warmer operating temperatures and decreased overall bypass times.

A Clinical Commentary on the Article “EMT-Inducing Biomaterials for Heart Valve Engineering: Taking Cues from Developmental Biology”

Attempts to engineer a heart valve substitute have been performed over the last two decades with significant progress achieved in cell biology, biomaterial composition, and biomechanical stimulation. Application of tissueengineering techniques has become clinically relevant in urology, orthopedics, plastic surgery, and otolaryngology, treating defined pathologic entities which improve patients quality of life and clinical practice [1]. From an epidemiologic standpoint, clinical relevance of tissue-engineered valves could affect millions of patients annually and alter the treatment algorithm for patients with both acquired and congenital valvar disease [2]. This manuscript offers insight into future biomaterials development utilizing techniques and advancements individually investigated. Combining the optimal mechanical properties achieved with electrospinning with biologic properties that support endothelial cell to mesenchymal cell transformation, a directed, possibly programmed, construct is plausible and the forefront of biomaterial design. Tissue-engineered constructs have a formidable task to meet and surpass current valve technology. While many cite the need for anticoagulation, the risk of calcification, limited durability, and the lack of growth potential as limitations, industry has made significant progress in mitigating these barriers. The stented bioprosthesis is the most utilized valve in clinical practice and has a low risk of thrombosis and thromboembolism. In most positions, the American Heart Association recommends an antiplatelet agent for anticoagulation, most often in the form of aspirin [3]. Anticalcification agents are proprietary for each valve and have improved with each generation of production. While data are being accrued, current shortand long-term follow-ups using both pericardial and porcine tissue valves show improved rates of calcification. Bioprosthetic valve durability has improved with each generation of valve design. Recent studies have shown maintenance of hemodynamics and bioprosthetic function up to 20 years in older patient cohorts [4]. The possibility of tissue-engineered heart valve growth with patient maturation could dramatically impact patient care. Valve companies have directed design and development effort to create catheter delivery systems with implantation in the pulmonary and aortic positions in the early stages of becoming accepted practice [5, 6]. By creating a stented valve that is expanded to conform to multiple defined size ranges, industry has created the first adjustable implant. As initial implants evaluate technique and efficacy, future investigation will include continued stent dilation and valve expansion as would be required for developing stenosis in the setting of somatic growth. Additionally, the less invasive techniques will impact reoperative open valve surgery. Clinical trials are being designed using catheter-inserted valves to replace previously placed valves in both the aortic and pulmonary positions (valve-in-a-valve concept) [7]. Current industry standards are elevating the benchmark required for clinical application of tissue-engineered heart valves as we continue to understand biologic principles This article is a commentary on the following article: 10.1007/s12265011-9300-4.