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Peripheral veno-artertial extracorporeal membrane oxygenation (VA-ECMO) is commonly used in the paediatric population for intractable respiratory and cardiac failure. One of the devastating complications of VA-ECMO is severe brain damage due to ischemia or haemorrhage. We describe a case of peripheral cervical VA-ECMO complicated by evolving right cerebral ischemia which was rescued with rapid conversion from peripheral to central VA-ECMO support. Notably, the patient had a complete circle of Willis. Following conversion, we observed complete resolution of neurological symptoms with full functional recovery. [ABSTRACT FROM AUTHOR]

Purpose Cardiopulmonary bypass induces an ischaemia-reperfusion injury and systemic inflammatory response, which contributes to low cardiac output syndrome following cardiac surgery. Exogenous nitric oxide during cardiopulmonary bypass has shown potential to ameliorate such injury. We undertook a large randomised controlled trial to investigate the clinical effects of administering nitric oxide to the cardiopulmonary bypass circuit in children. Methods After written informed consent, children were randomised to receive 20 ppm nitric oxide to the gas inflow of the cardiopulmonary bypass oxygenator, or standard conduct of bypass. Results 101 children received nitric oxide and developed low cardiac output syndrome less frequently (15 vs. 31 %, p = 0.007) than the 97 children who did not receive nitric oxide. This effect was most marked in children aged less than 6 weeks of age (20 vs. 52 %, p = 0.012) and in those aged 6 weeks to 2 years (6 vs. 24 %, p = 0.026), who also had significantly reduced ICU length of stay (43 vs. 84 h, p = 0.031). Low cardiac output syndrome was less frequent following more complex surgeries if nitric oxide was administered (17 vs. 48 %, p = 0.018). ECMO was used less often in the nitric oxide group (1 vs. 8 %, p = 0.014). Conclusions Delivery of nitric oxide to the oxygenator gas flow during paediatric cardiopulmonary bypass reduced the incidence of low cardiac output syndrome by varying degrees, according to age group and surgery complexity. Clinical Trial Registration: ACTRN12615001376538., Author(s): Christopher James [sup.1] [sup.2], Johnny Millar [sup.1] [sup.2], Stephen Horton [sup.2] [sup.3], Christian Brizard [sup.4], Charlotte Molesworth [sup.2], Warwick Butt [sup.1] [sup.2] [sup.5] Author Affiliations: (1) grid.416107.5, 0000000406140346, Department [...]

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease.Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021.Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685).Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels.Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups.Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery.Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392. [ABSTRACT FROM AUTHOR]

Objective: The aim of this review is to highlight an emerging problem with anticoagulation-related complications in neonatal and paediatric ECMO, to explore for flaws in the currently recommended anticoagulation management responsible for these problems and to discuss possible strategies mitigating further escalation of the issue. Data Sources: Pertinent neonatal and paediatric literature on the topic of interest and international Extracorporeal Life Support Organisation (ELSO) registry data request. Conclusions: The international ELSO registry data reveals increasing rates of anticoagulation-related complications during neonatal and paediatric ECMO worldwide. The causes are multifactorial and the proposed solution to the problem is to match anticoagulation management to the pathophysiological complexity of haemostasis on ECMO. [ABSTRACT FROM AUTHOR]

The horizontal-to-vertical (H/V) technique by Nakamura (1989) was applied to data from 30 new field stations and 64 other broadband temporary and permanent seismic stations within the Mississippi Embayment of the central United States to develop a 3D model of unconsolidated sediment shear-wave velocity structure. Using the Dart (1992) map of sediment thickness as a basis, two selfconsistent models of average shear-wave velocity versus sediment thickness were developed by utilizing the theoretical linear relationship between the frequency of the H/V peak and shear-wave velocity. One model was based on the observation that the H/V peak period Tp (s) versus sediment thickness h (m) was seen to be approximately linear with the relationship T p = 0.003266h + 1.084. The second model was developed by considering peak frequency f p versus sediment thickness parameterized to follow In /p = 8.325 × 10-7h² - 0.00232h - 0.01796. Overall, the models show low-average shear-wave velocity near the edge of the Mississippi Embayment with velocities increasing with increasing sediment thickness, consistent with increased sediment compaction. These models will be useful in studies of site resonance and amplification for earthquake-shaking hazards and for wave propagation computations for the region. [ABSTRACT FROM AUTHOR]

Objective: To characterize surface-bound proteins and to measure the thickness of fibrin fibers bound to extracorporeal membrane oxygenation (ECMO) circuits used in children., Design: Single-center observational prospective study, April to November 2021., Setting: PICU, Royal Children's Hospital, Melbourne, Australia., Patients: Patients aged less than 18 years on venoarterial ECMO and without preexisting disorder., Interventions: None., Measurements and Main Results: ECMO circuits were collected from six patients. Circuit samples were collected from five different sites, and subsequently processed for proteomic and scanning electron microscopy (SEM) studies. The concentration of proteins bound to ECMO circuit samples was measured using a bicinchoninic acid protein assay, whereas characterization of the bound proteome was performed using data-independent acquisition mass spectrometry. The Reactome Over-representation Pathway Analyses tool was used to identify functional pathways related to bound proteins. For the SEM studies, ECMO circuit samples were prepared and imaged, and the thickness of bound fibrin fibers was measured using the Fiji ImageJ software, version 1.53c (https://imagej.net/software/fiji/). Protein binding to ECMO circuit samples and fibrin networks showed significant intra-circuit and interpatient variation. The median (range) total protein concentration was 19.0 (0-76.9) μg/mL, and the median total number of proteins was 2011 (1435-2777). A total of 933 proteins were commonly bound to ECMO circuit samples from all patients and were functionally involved in 212 pathways, with signal transduction, cell cycle, and metabolism of proteins being the top three pathway categories. The median intra-circuit fibrin fiber thickness was 0.20 (0.15-0.24) μm, whereas the median interpatient fibrin fiber thickness was 0.18 (0.15-0.21) μm., Conclusions: In this report, we have characterized proteins and fiber fibrin thickness bound to ECMO circuits in six children. The techniques and approaches may be useful for investigating interactions between blood, coagulation, and the ECMO circuit and have the potential for circuit design., Competing Interests: Drs. McCafferty and Monagle’s institution received funding from the National Health and Medical Research Council (NHMRC) grant APP1129317. Dr. Attard’s institution received funding from the National Blood Authority, Bayer, and Janssen; he received funding from Anthos; he received support for article research from the NHMRC. Dr. MacLaren reported that he serves on the board of directors of the Extracorporeal Life Support Organization (unpaid). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Competing Interests: Disclosure: G.M. is the President of the Extracorporeal Life Support Organization (ELSO) (unpaid). The other authors have no conflicts of interest to report. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending royalties.

The continuous contact between blood and the foreign surface of the extracorporeal membrane oxygenation (ECMO) circuit contributes to hemostatic, inflammatory, and other physiological disturbances observed during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, cell adsorption to the ECMO circuit as an additional factor that could potentially influence clinical outcomes, has largely been overlooked. Here we provide a detailed immunofluorescence (IF) protocol designed to characterize cellular binding on ECMO circuits collected from patients. Extracorporeal membrane oxygenation circuits were collected from three pediatric patients and an albumin primed-only ECMO circuit was used as control. Circuit samples from five different sites within each ECMO circuit were collected and processed for the IF protocol. CD14 and CD42a antibodies were used to identify platelets and leukocytes bound to each ECMO circuit sample and images captured using inverted fluorescence microscopy. The protocol enables the comprehensive characterization of platelet and leukocyte binding to ECMO circuits collected from patients, which could in turn extend our knowledge of the characteristics of circuit binding and may provide guidance for improved ECMO circuit design., Competing Interests: G.M. is the president of the Extracorporeal Life Support Organization (ELSO). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392., Competing Interests: Yves d’Udekem receives consultancy fees from Actelion (Janssen) and travel fees from Berlin Heart., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)