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Introduction: Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol., Methods and Analysis: The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery., Ethics and Dissemination: The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal., Trial Registration Number: ACTRN12617000821392., Competing Interests: Competing interests: YdU is a consultant for MSD and Actelion., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In 2011 we reported unfavourable outcomes of second-run extracorporeal life support (ECLS) in children. We wanted to investigate whether this previous report affected our strategy and modified our long-term outcomes., Methods: Between 1988 and 2015, 31 patients underwent a second-run ECLS. Median age at the time of first support was 9days (0-16 years). Median length of support for the first and second runs were 4.7days (0.1-10) and 3.6days (0.5-8.7) respectively, with an interval of 1.8days (0.1-66) between supports., Results: There was an increasing trend in the number of patients undergoing second-run ECLS after our report: 21 patients between 1988 and mid-2010 (0.9 patients/year) and 10 between mid-2010 and 2015 (two patients/year) (p=0.06). However, among all the patients who underwent ECLS, the proportion of second-run ECLS was not different before and after 2010 (4% vs. 4.2% respectively, p=0.92). While 58% of patients (18/31) survived weaning of support, only 23% (7/31) survived to hospital discharge and 14% (5/31) were still alive after hospital discharge at a median of 6.5 years (1.2-11.6). The three patients who had positive long-term outcomes had the second-run ECLS instituted to allow for major cardiac operations., Conclusions: Compassionate use of second-run ECLS is difficult to refuse but one should be aware that its outcomes are dismal. In our centre, benefits seem to be limited to cases where the second-run ECLS allows for a major cardiac intervention., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: The myocardial protective effect of remote ischemic preconditioning has been demonstrated in heterogeneous groups of patients undergoing cardiac surgery. No studies have examined this technique in neonates. The present study was performed to examine the remote ischemic preconditioning efficacy in this high-risk patient group., Methods: A preliminary, randomized, controlled trial was conducted to investigate whether remote ischemic preconditioning in cyanosed neonates undergoing cardiac surgery confers protection against cardiopulmonary bypass. Two groups of neonates undergoing cardiac surgery were recruited for the present study: patients with transposition of the great arteries undergoing the arterial switch procedure and patients with hypoplastic left heart syndrome undergoing the Norwood procedure. The subjects were randomized to the remote ischemic preconditioning or sham control groups. Remote ischemic preconditioning was induced by four 5-minute cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Troponin I and the biomarkers for renal and cerebral injury were measured pre- and postoperatively., Results: A total of 39 neonates were recruited-20 with transposition of the great arteries and 19 with hypoplastic left heart syndrome. Of the 39 neonates, 20 were randomized to remote ischemic preconditioning and 19 to the sham control group. The baseline demographics appeared similar between the randomized groups. The cardiopulmonary bypass and crossclamp times were not significantly different between the 2 groups. The troponin I levels were not significantly different at 6 hours after cardiopulmonary bypass nor were the postoperative inotrope requirements. Markers of renal (neutrophil gelatinase-associated lipocalin) and cerebral injury (S100b, neuron-specific enolase) were not significantly different between the 2 groups., Conclusions: Our data suggest that remote ischemic preconditioning in hypoxic neonates undergoing cardiopulmonary bypass surgery does not provide myocardial, renal, or neuronal protection. Additional studies are needed to examine the relationships among developmental age, hypoxia, and the molecular mechanisms of ischemic preconditioning., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Systemic cooling for cardiopulmonary bypass is widely used to attenuate the systemic inflammatory response syndrome and organ injury in children after open surgery. We compared the effects of moderate (24 °C) and mild (34 °C) hypothermia during bypass on markers of the systemic inflammatory response syndrome and organ injury, and on clinical outcome after corrective surgery for congenital heart disease., Methods: Sixty-six children (mean age, 6.8 ± 5.7 months; mean weight, 6.2 ± 2.3 kg) were randomized to 24 °C or 34 °C bypass temperature during cardiac surgery. Perfusion strategies were otherwise strictly identical. Clinical data and blood samples were collected before bypass, 5 minutes after aortic crossclamp release, and 4, 24, and 48 hours after bypass. Patients were followed up until discharge from the hospital., Results: In the 54 children with outcome data, bypass temperature did not influence the duration of mechanical ventilation between the 24 °C group and the 34 °C group (median [interquartile range] 22 [13-40] hours vs 14 [8-40] hours, P = .14), intensive care unit stay (43 [24-49] hours vs 29 [23-47] hours, P = .79), blood loss (29 [20-38] mL/kg vs 23 [13-38] mL/kg, P = .36), or incidence of postoperative infection (9% vs 11%, P = 1.0). There was no evidence of an influence of bypass temperature on the markers of acute inflammation, innate immune response, organ injury, coagulation, or hemodynamics., Conclusions: There is no evidence that the systemic inflammatory response syndrome and organ injury after pediatric open surgery are influenced by bypass temperature. The routine use of hypothermic bypass may not be warranted in the pediatric population., (Copyright © 2011 The American Association for Thoracic Surgery. All rights reserved.)

Centrifugal pump left ventricular assist device is a useful adjunct in pediatric cardiac surgery, as a bridge to recovery, or in some cases, to transplantation. This form of circulatory support may not have the universal applicability of extracorporeal membrane oxygenation, but it is equally or more effective in properly selected patients. The technology for centrifugal pump support is now quite standardized, and the advantages well documented. In this chapter we discuss the problems of indications, case selection, technical aspects of the circuit, and general clinical management. Results since 1989 are also presented.