OBJECTIVES:To describe our use and experience with an "in-series" approach for patients requiring both continuous renal replacement therapy (CRRT) as well as therapeutic plasma exchange (TPE).DESIGN:Retrospective review of case notes.SETTING:General and cardiac PICUs at the Royal Children's Hospital in Melbourne, VIC, Australia.PATIENTS:Children (0-18 yr old) requiring both CRRT and TPE between 2018 and 2022.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Twelve children were successfully and safely treated with 32 TPE sessions and 38 CRRT sessions with our in-series CRRT and TPE setup using a total of 20 extracorporeal circuits and 11 additional plasma filters or hemofilters. This represents a reduction of 71% in standard circuit usage.CONCLUSIONS:Our approach to providing "in-series" CRRT and TPE used existing access and circuits, a single device, and resulted in efficient treatments, reduced infection risk, reduced exposure to circuits, less hemodilution, and less blood product use. Small potential cost and waste reductions were also achieved. This approach was performed safely with no unexpected adverse events.

Objectives:To describe the contemporary practice of analgesia and sedation in children in intensive care units (ICU) in Australia and New Zealand (ANZ). Design:A unit level survey. Setting:ICUs in Australia and New Zealand between December 2024 and May 2025. Participants:ICUs that admit more than 150 children annually and report data to the Australian and New Zealand Paediatric Intensive Care Registry. Main outcome measures:Protocols for analgesia, sedation, delirium and iatrogenic withdrawal syndrome (IWS) as well as medication preferences and quality initiatives related to analgesia and sedation. Results:Fourteen of the 16 eligible ICUs completed the survey. Analgesia and sedation protocols were reported by seven tertiary paediatric ICUs (7/9) compared to two general units (adult/paediatric and combined neonatal/paediatric ICUs) (2/5). The preferred first line analgesic was morphine, and first line sedative was dexmedetomidine, however reported sedative preferences varied. Protocolised pain assessment tools were universally reported, sedation assessments were reported in 13/14 units, iatrogenic withdrawal assessments in 12/14 units and less than half (6/14) reported protocolised delirium assessment. Protocols for neuromuscular blocking agent use were also reported in 6/14 ICUs. Multidisciplinary quality assurance groups were infrequent (4/14 ICUs). Conclusions:Paediatric analgesia and sedation protocols were reported in nearly two-thirds of ICUs in ANZ that care for children and more commonly in tertiary PICUs. Analgesia, sedation and drug withdrawal protocolisation were common however, less so for delirium. Despite the multiple components of analgesia and sedation management, governance and quality assurance programs were uncommon.

STUDY QUESTION:To describe the blood product utilization during neonatal and pediatric extracorporeal membrane oxygenation (ECMO) and to determine whether its usage correlates with clinical outcomes of bleeding, thrombosis or mortality. DESIGN:Prospective observational study of neonatal and pediatric ECMO patients from September 2016, until January 2022. SETTING:Tertiary center for pediatric and neonatal ECMO. PATIENTS:One hundred and ten runs of ECMO, nine patients had two runs of ECMO during the same hospital admission. RESULTS:All patients received at least one red blood cell (RBC) transfusion. RBCs, as well as fresh frozen plasma (FFP), platelets and cryoprecipitate transfusion, as well as total donor exposure did not predict increased mortality in ECMO patients. Increased volume of platelets was associated with patients who bled, but not those who had a thrombosis or died. DISCUSSION:This prospective cohort study failed to demonstrate that the volume of red blood cells, FFP and platelets or total donor exposure was predictive of increased mortality. Of particular importance is the lack of increased volume of red blood cells transfused to patients who experienced major bleeding events compared to those who did not, suggesting that the trigger for transfusions may not be based on the clinical status of bleeding and resultant Hb in isolation.

Objective:Peritoneal dialysis (PD) commenced early in the postoperative period has the potential to mitigate the postcardiopulmonary bypass inflammatory response. We evaluated the role of early PD on postoperative outcomes after the arterial switch operation (ASO). Methods:Newborns (≤30 days, n = 318) undergoing ASO were classified into those who did (early PD, n = 90) or did not (control, n = 228) receive PD within 6 hours of admission to intensive care unit after surgery. Using observational data and imitating a preplanned clinical trial (target trial framework), we evaluated the role of early PD on postoperative outcomes. Results:Infants in the early PD group had greater serum lactate (median [interquartile range]: 2.6 [2.1, 4.1] vs 2.2 [1.8, 2.9]) and lower central venous saturation (median [interquartile range]: 45.2 [39.3, 51.4] vs 51.3 [42.2, 59.9]) at admission. Early PD was associated with a shorter duration of mechanical ventilation, but this effect was restricted to the subgroup receiving extracorporeal membrane oxygenation (ECMO) in the perioperative period (incidence rate ratio [95% confidence interval]: for early PD/control: 0.28 [0.17-0.47] for those requiring ECMO and 1.14 [0.93-1.39] for those not requiring ECMO, P interaction <.001). Similar results were seen for intensive care unit length of stay. Conclusions:Early PD after ASO was associated with a reduction in duration of mechanical ventilation and intensive care stay for infants who required ECMO in the perioperative period. Future studies of early PD, ideally clinical trials, in high-risk infants (such as those requiring ECMO after cardiac surgery) will be of benefit to either confirm or refute these findings.

Objectives: Pediatric sepsis results in significant morbidity and mortality worldwide. There is an urgent need to investigate adjunctive therapies that can be administered early. We hypothesize that using vitamin C combined with hydrocortisone increases survival free of inotropes/vasopressors support until day 7 compared with standard care. Here we describe the Resuscitation in Paediatric Septic Shock using Vitamin C and Hydrocortisone (RESPOND) trial protocol, which aims to address this hypothesis. Design: Randomized, open label, controlled, parallel-group, three-arm trial with integrated economic evaluation. Setting: Nine Australia and New Zealand PICUs, with interest from additional international sites. Patients: Children between 7 days and younger than 18 years old who are treated for suspected or confirmed sepsis and receiving inotropes/vasopressors for greater than 1 hour. Interventions: IV vitamin C (100 mg/kg [maximum 5 g] every 6 hr) and hydrocortisone (1 mg/kg [maximum 50 mg] every 6 hr), or IV hydrocortisone alone (1 mg/kg [maximum 50 mg] every 6 hr) or standard care. Measurements and Main Results: Three hundred eighty-four children will be randomly assigned to receive the interventions, or standard care in a 1:1:1 ratio with stratification by steroid administration pre-randomization and hospital site. The primary outcome is time alive and free of inotropes/vasopressors, censored at 7 days. Secondary outcomes include 28-day mortality, survival free of organ support, PICU length of stay, quality of life, functional status and neurodevelopmental vulnerability at 6 months post-enrollment, and hospitalization-related costs. Statistical analysis will be based on an intention-to-treat principle. The study has ethical approval (HREC/20/QCHQ/69922, dated December 21, 2020), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12621000247875), commenced recruitment on December 8, 2021, and is expected to finish recruitment by mid-2026. Conclusions: Dissemination of the results will occur through publication in peer-reviewed journals, presentations at international conferences, and additional consumer-informed pathways.

OBJECTIVES:To determine if a priori standardization of outcome hemostatic definitions alone was adequate to enable useful comparison between two cohorts of pediatric extracorporeal membrane oxygenation (ECMO) patients, managed according to local practice and protocol. DESIGN:Comparison of two separate prospective cohort studies performed at different centers with standardized outcome definitions agreed upon a priori. SETTING:General and cardiac PICUs at the Royal Children's Hospital (RCH) in Melbourne, Australia, and the Sophia Children's Hospital (SCH) in Rotterdam, The Netherlands. PATIENTS:Children (0-18 yr old) undergoing ECMO. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Although outcome definitions were standardized a priori, the interpretation of surgical interventions varied. The SCH study included 47 ECMO runs (September 2019 to April 2023), and the RCH study included 97 ECMO runs (September 2016 to Jan 2022). Significant differences in patient populations were noted. RCH patients biased toward frequent cardiac ECMO indications, central cannulation, and cardiopulmonary bypass before ECMO. The frequency of outcome ascertainment was not standardized. CONCLUSIONS:This international comparison shows that standardizing hemostatic outcome definitions alone is insufficient for sensible comparison. Uniform interpretation of definitions, consistent frequency of outcome ascertainment, and stratification based on patient populations and ECMO practices are required. Our results highlight the granularity of detail needed for cross-center comparison of hemostatic outcomes in pediatric ECMO. Further work is needed as we move toward potential multicenter trials of pediatric ECMO.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations.

OBJECTIVES:The aim of this study was to (i) evaluate follow-up services in Australia and New Zealand for children surviving paediatric intensive care; (ii) assess clinician and service-wide knowledge of post-intensive care syndrome-paediatrics; and (iii) identify barriers to long-term follow-up services post paediatric intensive care unit admission. METHODS:Two cross-sectional, web-based REDCap surveys were designed for organisational leadership and individual clinician respondents. All paediatric intensive care units with staffed paediatric beds in Australia and New Zealand were invited to participate. RESULTS:Eleven paediatric intensive care units and 345 clinicians responded to the two surveys. None of the 11 paediatric intensive care units reported having any dedicated outpatient follow-up services. Only 53% of clinicians had heard of the term post-intensive care syndrome-paediatrics prior to the survey. However, most clinicians believed that follow-up care should be provided to children following a paediatric intensive care unit admission (96%) via a combination of modalities (49%) (e.g., telehealth and face-to-face) conducted by a multidisciplinary team (32%). Both the individual clinicians and the organisational leadership respondents identified staffing and budget restraints as the biggest barriers to follow-up care. CONCLUSIONS:Despite growing international evidence to support the implementation of paediatric intensive care unit follow-up services, Australian and New Zealand paediatric intensive care units do not currently offer such services. In implementing paediatric intensive care unit follow-up practices, staffing and budgetary restraints need to be addressed. Improving clinician- and organisation-wide awareness and understanding of post-intensive care syndrome-paediatrics and its impacts may also help to reduce barriers to implementing follow-up services in Australian and New Zealand paediatric intensive care units.

Despite the challenges posed by vast geographical distances and relatively small populations (Australia: 26 million, New Zealand: 5 million), Australia and New Zealand (ANZ) are renowned for their high quality innovative pediatric intensive care research. A strong culture of partnership across units led to the formation of the ANZ Intensive Care Society Paediatric Study Group (ANZICS PSG) in 2003, which has evolved since its formation into one of the leading international pediatric intensive care trial networks, along with two in the United States (1, 2) and one in the United Kingdom (3). Here, we describe the factors leading to the growth of the ANZICS PSG, explore the current established research ecosystem, along with future plans to sustain success.

Importance Children with congenital heart defects who undergo cardiopulmonary bypass (CPB) surgery are at risk for delayed or impaired neurodevelopmental outcomes. Nitric oxide (NO) added to the CPB oxygenator may reduce systemic inflammation due to CPB and improve recovery from surgery, including improved neurodevelopmental outcomes. Objective To investigate neurodevelopment, health-related quality of life (HRQOL), and factors associated with impaired neurodevelopment at 12 months post surgery in infants who received CPB with NO or standard CPB. Design, Setting, and Participants This double-masked randomized clinical trial was conducted in 6 centers in Australia, New Zealand, and the Netherlands between July 19, 2017, and April 28, 2021, with a preplanned prospective follow-up 12 months postrandomization completed on August 5, 2022. The cohort included 1364 infants younger than 2 years who underwent open heart surgery with CPB for congenital heart disease. Interventions The intervention group received NO 20 ppm into the CPB oxygenator. The control group received standard CPB. Main Outcomes and Measures The primary outcome was neurodevelopment, defined as the Ages and Stages Questionnaire, Third Edition (ASQ-3) total score. Secondary outcomes were HRQOL and functional status as measured by Pediatric Quality of Life Inventory and modified Pediatric Overall Performance Category scores, respectively. Sensitivity analyses modeled the outcome for patients lost to follow-up. Results Of 1318 infants alive 12 months after randomization, follow-up was performed in 927, with 462 patients in the NO group and 465 in the standard care group (median [IQR] age at follow-up, 16.6 [13.7-19.8] months; median [IQR] time since randomization, 12.7 [12.1-13.9] months; 516 male [55.7%]). There were no differences between the NO and standard care groups in ASQ-3 total score (mean [SD], 196.6 [75.4] vs 198.7 [73.8], respectively; adjusted mean difference, −2.24; 95% CI, −11.84 to 7.36). There were no differences in secondary outcomes. Prematurity (gestational age <37 weeks), univentricular lesions, congenital syndromes, and longer intensive care unit length of stay were associated with lower ASQ-3 total scores in adjusted multivariable analyses. Conclusions and Relevance In this randomized clinical trial of infants with congenital heart disease, NO administered via the CPB oxygenator did not improve neurodevelopmental outcomes or HRQOL 12 months after open heart surgery. Further research should explore homogenous cohorts with higher surgical risk and higher-dose or alternative therapies. Trial Registration ANZCTR Identifier: ACTRN12617000821392

BackgroundRed cell transufion in veno-arterial membrane oxygenation (VA ECMO) has been widely debated.PurposeThis narrative review aims to examine the historical and current approaches of red cell transfusion in veno-arterial extracorporeal membrane oxygenation (VA ECMO) to enhance oxygen delivery. It will explore the potential benefits and pitfalls of red blood cell (RBC) transfusion in VA ECMO, including relationship between haemoglobin (Hb) concentration, tissue oxygenation and patient outcomes associated with transfusion. Following it will review the impact of cardiogenic shock on the microcirculation, performance of transfused RBC and effects of the ECMO circuit on RBC function. It will conclude with an introduction to potential mechanisms by which we might manipulate red cells to improve tissue oxygenation, without augmentation of Hb concentration.ConclusionFurther research is needed to provide insight into optimal RBC transfusion thresholds and strategies to augment red cell function to optimise tissue oxygenation in VA ECMO.

Importance:Children with congenital heart defects who undergo cardiopulmonary bypass (CPB) surgery are at risk for delayed or impaired neurodevelopmental outcomes. Nitric oxide (NO) added to the CPB oxygenator may reduce systemic inflammation due to CPB and improve recovery from surgery, including improved neurodevelopmental outcomes. Objective:To investigate neurodevelopment, health-related quality of life (HRQOL), and factors associated with impaired neurodevelopment at 12 months post surgery in infants who received CPB with NO or standard CPB. Design, Setting, and Participants:This double-masked randomized clinical trial was conducted in 6 centers in Australia, New Zealand, and the Netherlands between July 19, 2017, and April 28, 2021, with a preplanned prospective follow-up 12 months postrandomization completed on August 5, 2022. The cohort included 1364 infants younger than 2 years who underwent open heart surgery with CPB for congenital heart disease. Interventions:The intervention group received NO 20 ppm into the CPB oxygenator. The control group received standard CPB. Main Outcomes and Measures:The primary outcome was neurodevelopment, defined as the Ages and Stages Questionnaire, Third Edition (ASQ-3) total score. Secondary outcomes were HRQOL and functional status as measured by Pediatric Quality of Life Inventory and modified Pediatric Overall Performance Category scores, respectively. Sensitivity analyses modeled the outcome for patients lost to follow-up. Results:Of 1318 infants alive 12 months after randomization, follow-up was performed in 927, with 462 patients in the NO group and 465 in the standard care group (median [IQR] age at follow-up, 16.6 [13.7-19.8] months; median [IQR] time since randomization, 12.7 [12.1-13.9] months; 516 male [55.7%]). There were no differences between the NO and standard care groups in ASQ-3 total score (mean [SD], 196.6 [75.4] vs 198.7 [73.8], respectively; adjusted mean difference, -2.24; 95% CI, -11.84 to 7.36). There were no differences in secondary outcomes. Prematurity (gestational age <37 weeks), univentricular lesions, congenital syndromes, and longer intensive care unit length of stay were associated with lower ASQ-3 total scores in adjusted multivariable analyses. Conclusions and Relevance:In this randomized clinical trial of infants with congenital heart disease, NO administered via the CPB oxygenator did not improve neurodevelopmental outcomes or HRQOL 12 months after open heart surgery. Further research should explore homogenous cohorts with higher surgical risk and higher-dose or alternative therapies. Trial Registration:ANZCTR Identifier: ACTRN12617000821392.

Background:Vasoactive agents are a critical supportive therapy for children with sepsis. We describe the choice and use patterns of vasoactive agents in children with sepsis. Methods:Prospective observational study conducted in 11 hospitals in Australia and New Zealand through the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network from April 2021 to December 2023. Children aged 0-<18 years with suspected sepsis were included. Children admitted to hospital and treated with parenteral antibiotics and either 1) a provisional diagnosis of sepsis, and/or 2) treatment for suspected sepsis (fluid bolus to treat poor perfusion). The frequency and sequence of use of vasoactive agents, and contributors to the choice of initial vasoactive were collected. Findings:6232 children with suspected sepsis were included; median age of 2.1 years (IQR 0.3-7.1 years), in-hospital mortality of 60 (1.0%), in whom a subset of 306 (4.9%) met Phoenix sepsis criteria. Vasoactive agents were used in 179 (2.9%) children overall and in 144 (45.8%) of those meeting Phoenix sepsis criteria. The most used first, second, and third-line vasoactive agents were adrenaline (90/179; 50.3%), noradrenaline (49/91; 53.8%), and vasopressin (16/40; 40.0%). When comparing noradrenaline vs adrenaline as first line agents, increasing age was associated with preferential use of noradrenaline (RR 1.06, 95% CI 1.03-1.09; p < 0.001). Interpretation:Children with suspected community acquired sepsis rarely received treatment with vasoactive agents. Adrenaline and noradrenaline were the most used agents, though there was substantial variation in their use and sequencing. Funding:This study is funded in part by a National Health and Medical Research Council (NHMRC) Medical Research Future Fund grant (GNT1190814). The full list of funders is presented at the end of the paper.

Over the last 40 years, extracorporeal organ support therapy (ECOST) has become a routine therapy for many critically ill children, cared for in a PICU. The types of modalities used include renal replacement therapy (RRT), hemadsorption, molecular adsorbent recirculating system (MARS), total plasma exchange (TPE), extracorporeal membrane oxygenation (ECMO), and mechanical circulatory support (MCS). All of these technologies have similar issues associated with their use in clinical medicine, namely: 1) vascular access, 2) equipment failure, 3) infection, 4) thromboembolism, and 5) hemorrhage. Anticoagulation of these circuits is essential to maintain their functionality, but as ECOST has been increasingly applied to children with more complex clinical diseases, such as septic shock, liver failure, etc (and these patients will have very complex hematological problems with both increased risks of thrombosis and increased risks of bleeding), the management of circuit anticoagulation has had to be modified to deal safely with these situations. The choices include: 1) systemic heparin (targeted to an activated clotting time [ACT], activated partial thromboplastin time [APTT], or anti-Xa); 2) regional citrate anticoagulation (targeted to an ionized calcium); 3) bivalirudin (targeted to an APTT); or 4) antiplatelet drugs (which may be monitored by modern thromboelastography). Decisions about which type of anticoagulation should or could be used require consideration about patient factors (primary disease and relevant comorbidities, severity of illness and most importantly coagulation status of the patient, both thrombotic and bleeding risks) and effectiveness and complications of the various anticoagulants (as well as the ability to monitor and target medication to a safe therapeutic level). However, before we consider these issues, let us remind ourselves of the blood-foreign surface interaction. When blood comes in to contact with a foreign surface, an unbalanced activation of coagulation is initiated with plasma proteins, predominantly fibrinogen, which is adsorbed to the surface, which then leads to platelet entrapment, aggregation and activation with an ensuing complement activation, inflammatory response with cytokines and chemokines attracting leucocytes (1,2). Without anticoagulation, this process would continue and lead to clotting of the circuit. Currently, there are a number of strategies used to modify the surface of the tubing and devices to minimize the blood-surface interaction (3). These include a range of substances and methods, such as polymers that reduce surface tension and thus reduce cellular and protein adhesion (polycaprolactone-polydimethylsiloxane-polycaprolactone phosphorylcholine) or ionic or covalently bonded heparin (4) (anticoagulant) polyethylene oxide (hydrophilic), sulphate and sulfonate groups (negative charge), albumin (5) (decreases fibrinogen binding), or nitric oxide (6) (anticoagulant). Despite these improvements, which do lengthen filter/circuit survival, some form of anticoagulation is still required. There are pros and cons of each method of anticoagulation. Heparin can be given as a systemic targeted therapy (to ACT or APTT) or as a regional therapy with protamine reversal, but both carry risks of increased bleeding (heparin-protamine complex itself is an anticoagulant) and possible heparin-induced thrombocytopenia (with severe intravascular thrombosis). Regional citrate anticoagulation is very effective but potentially has substantial risks, especially in acute liver failure, with the development of metabolic alkalosis and rarely citrate toxicity (with hypocalcemia, hypomagnesemia, hypotension, cardiac arrhythmias, and lactic acidosis). Bivalirudin is increasingly being used for ECMO and MCS but only rarely in RRT or TPE. A cocktail of drugs targeting different players in the complex blood-foreign surface interaction might represent a future strategy for managing children on ECOST. By administering epoprostenol with standard UFH, similar ACT targets can be achieved with a lower heparin dose and potentially less bleeding driven by excessive inhibition of the clotting cascade. A recent review of the use of prostacyclin in adults confirmed its effectiveness and safety as an anticoagulant in RRT, MARS, and ECMO (7). One important reason that antiplatelet drugs have had limited use as an anticoagulant in PICU is the difficulty in “point of care” monitoring of platelet function. Laboratory tests of platelet function have also been difficult to integrate into routine clinical practice with therapeutic targets (degree of platelet inhibition) being unclear. However, over the last 15 years, there has been increasing use of thromboelastography and platelet mapping, which have improved the management of complex clinical situations in which major bleeding and transfusion can occur (such as cardiac surgery, trauma, and liver failure). Thromboelastography is a viscoelastic hemostatic assay that measures various aspects of whole blood clot formation. The thromboelastography shows the interaction of platelets with the coagulation cascade by showing the time to clot formation (R time), the rate of clot formation, that is., coagulability of blood (K time and alpha angle in degrees), the strength of the clot (maximum amplitude in mm), and the stability of clot (presence or absence of fibrinolysis over time). In more detail, the: 1) R value is the reaction time (s), this is the time of latency from start of test to initial fibrin formation (amplitude of 2 mm) and is dependent on clotting factors; 2) K is the kinetics (s) which is the time taken to achieve a clot strength of 20 mm amplitude and is dependent on fibrinogen; 3) alpha is the angle (slope of line between R and K) and measures the speed at which fibrin build up and cross-linking takes place; hence, assesses the rate of clot formation and is dependent on fibrinogen; 4) TMA is the time to maximum amplitude; 5) MA is the maximum amplitude (mm) which represents the ultimate strength of the fibrin clot and is dependent on platelets (80%) and fibrin (20%); and 6) LY30 is the amplitude at 30 minutes, which is the percentage decrease in amplitude at 30 minutes post-MA and represents fibrinolysis phase. This knowledge allows a clear approach to treatment: patients with an increased R time receiving FFP, a decreased alpha angle having cryoprecipitate, a decreased MA receiving platelets, and presence of fibrinolysis treated with tranexamic acid or aminocaproic acid. Although normal thromboelastography ranges have been identified for healthy children and correlated with standard anticoagulation tests (8), therapeutic cutoffs to drive anticoagulation on ECMO in children are lacking. Platelet mapping provides information on the degree of platelet inhibition by having the normal thromboelastography and then a separate cartridge which has four assays—the first assay uses a Kaolin activator to produce a strong thrombin response to maximally activate all platelets and cleave all fibrinogen demonstrating underlying potential for maximum clot strength. The second assay blocks thrombin and shows clot strength from fibrin. The third and fourth assays block thrombin effects and stimulate platelets to aggregate via the adenosine diphosphate-activated receptors or the thromboxane A2 receptor showing clot strength. The degree of inhibition (by the antiplatelet medication or disease) is thus calculated after being compared with the patients’ baseline (clot strength without the stimulation). The thromboelastography and platelet mapping now allow point of care testing that provides increased knowledge of anticoagulation, based on whole blood clotting, and specifically gives a quantifiable understanding of the degree of platelet inhibition. This allows titratable dosing of antiplatelet medication, which will likely improve efficacy and safety. In this issue of Pediatric Critical Care Medicine, Deep et al (9) present their experience of 10 years’ use of prostacyclin in children with acute liver failure receiving RRT. Briefly, 96 patients receiving 353 episodes of RRT lasting 18,508 hours with a median filter life of 48 hours. Major bleeding occurred in ~ 6% and minor bleeding in 5% of episodes; hypotension occurred in 11.6%. The frequency of bleeding is similar to published studies with other types of anticoagulants despite the presence of a complex clinical situation with liver disease and coagulopathy. Although these data represent patients treated between 2010 and 2019, the use of epoprostenol has continued. The most important part of this article is located in the Supplementary Digital Content File 1 (9), which is the epoprostenol protocol of Kings College Hospital. This brief document provides a template for those wishing to use prostacyclin as an anticoagulant when there are safety concerns in relation to the use of heparin or citrate or any other reason to use an IV drug that impairs platelet aggregation. This document highlights all aspects of preparation, administration, infusion rates, complications, and strategies to deal with the complications. The major side effect of prostacyclin is vasodilation and hypotension which mandates continuous monitoring of blood pressure but given the short half-life is readily reversible. Other potential side effects include changes in heart rate, hypoxemia due to ventilation perfusion mismatch (due to abolition of hypoxic pulmonary vasoconstriction), and hyperglycemia. Deep et al (9) have clearly demonstrated the safety and effectiveness of prostacyclin as an anticoagulant in RRT for children with liver disease; this now presents a possible alternative anticoagulant therapy in other clinical situations. Interestingly, although at our hospital in Melbourne, we have used prostacyclin as an anticoagulant in patients receiving ECMO or VAD, we have not used it in RRT for children with or without, liver failure. Having now seen Deep et al (9) work that practice may change!

ObjectivePrenatal diagnosis of transposition of great arteries (TGA) is expected to improve postoperative outcomes after neonatal arterial switch operation (ASO); however, published reports give conflicting results. We aimed to determine the association between prenatal diagnosis and early postoperative outcomes after neonatal ASO.MethodsCohort study involving 243 newborns who underwent ASO (70% prenatally diagnosed) between 2010 and 2019. Multivariable regression was used to determine the association between prenatal diagnosis and (a) birth characteristics and (b) postoperative outcomes.ResultsGestational age and birthweight centile were lower and small-for-gestational-age more common (11.8% vs 1.4%) in those diagnosed prenatally. Among births which followed labour induction or prelabour caesarean, prenatal diagnosis was associated with earlier gestation at birth (mean (SD), 38.5 (1.6) vs 39.2 (1.4), p=0.01). Among births which followed spontaneous labour, prenatal diagnosis was associated with earlier gestation at labour onset (38.2 (1.8) vs 39.2 (1.4), p=0.01). Prenatal diagnosis was associated with longer postoperative mechanical ventilation (incidence rate ratio 1.74, 95% CI 1.37 to 2.21), intensive care (1.70, 1.31 to 2.21) and hospital length of stay (1.37, 1.14 to 1.66) after ASO. Gestational age mediated up to 60% of the effect of prenatal diagnosis on postoperative outcomes.ConclusionAmong newborns undergoing ASO for TGA, prenatal diagnosis is associated with poorer early postoperative outcomes. In addition to minimising iatrogenic factors (such as planned births) resulting in earlier births, evaluation of other dynamics following a prenatal diagnosis which may result in poor fetal growth and earlier onset of spontaneous labour is important.

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.

Objectives To investigate the validity of a 19-point clinical edema score (CES) and mid-limb circumferences for quantifying edema. Methods A prospective exploratory study was performed in mechanically ventilated children after cardiac surgery in a tertiary pediatric intensive care unit (PICU). Body weight, a CES, and mid-limb circumferences were performed at baseline and two consecutive 24-h intervals. Results We studied fifty-nine children with a median age of 8.0 days [IQR; 1.0, 14.0]. Body weight and edema measurements were performed at enrolment (baseline) and two subsequent 24-h time points. Between baseline and 24 h, the median change in body weight was −33g [IQR; −146, 106], and between 24 and 48 h, −97g [IQR; −241, −28]. Changes in the CES and leg circumference, but not arm circumference, were significantly associated with small changes in body weight. In a multivariable linear, mixed effects model, accounting for repeated measures within children and baseline values, there was statistically significant evidence that every point increase in CES was associated with an increase of 12.6 g [95%CI; 3.6–21.5] in body weight. Similarly, a 1-cm increase in leg circumference was associated with an increase in body weight of 46.7 g [95%CI; 3.5–89.9]. However, there was no statistically significant association between arm circumference and body weight. Conclusions In children after cardiac surgery, a CES and leg circumference, but not arm circumference, may be a valid measure of fluid accumulation. Larger studies in broader populations of critically ill children are warranted.