High risk of necrotising enterocolitis in term-born neonates with CHD delivered by caesarean section: a case-control study.

OBJECTIVE: Necrotising enterocolitis is linked with altered intestinal microbiota, and caesarean birth is associated with imbalance of newborn intestinal microbiome. We aimed to investigate the role of delivery mode (vaginal or caesarean) and gestational age in the development of necrotising enterocolitis among term-born neonates (≥ 37 weeks) with CHD. METHODS: Case-control study. We studied all newborns with CHD who underwent cardiac surgery during the neonatal (≤ 28 days of age) period, between 2007 and 2017. Totally, 60 cases of necrotising enterocolitis were matched (by year of birth and type of congenital heart lesion) with 180 controls (1:3 ratio). Multivariable conditional logistic regression was used to assess the study question. RESULTS: The overall prevalence of necrotising enterocolitis was 6.3% in term-born newborns with CHD. Neonates with a left-ventricular outflow tract lesion or single ventricle lesion accounted for 55% (n = 33) of cases. 62% (n = 37) cases were in the modified Bell's stage 2 or more for necrotising enterocolitis classification. In multivariable modelling, gestational age at birth was not associated with the development of necrotising enterocolitis [adjusted odds ratio per week increase, 95% confidence interval: 1.20 (0.90-1.60)]. Birth by caesarean delivery (compared to vaginal) was strongly associated with development of necrotising enterocolitis [adjusted odds ratio (95% confidence interval): 2.64 (1.31-5.29)]. We failed to identify an association between preoperative enteral nutrition and necrotising enterocolitis. CONCLUSION: This study showed a high risk of necrotising enterocolitis in newborns with critical CHD born via caesarean. This information is important given the high prevalence of planned birth by caesarean in newborns with CHD.

Agreement Between Measured Weight and Fluid Balance in Mechanically Ventilated Children in Intensive Care.

OBJECTIVES: To investigate the agreement between change in body weight (BW) and fluid balance (FB), and the precision and safety of BW measurement in mechanically ventilated infants in intensive care. DESIGN: Prospective observational study. SETTING: Tertiary PICU. PATIENTS: Infants following cardiac surgery, at baseline, 24 hours, and 48 hours. INTERVENTIONS: BW and FB measurement at three time points. MEASUREMENTS AND MAIN RESULTS: Between May 2021 and September 2022, we studied 61 children. The median age was 8 days (interquartile range [IQR], 1.0-14.0 d). The median BW at baseline was 3,518 g (IQR, 3,134-3,928 g). Change in BW was -36 g (IQR, -145 to 105 g) and -97 g (IQR, -240 to -28 g) between baseline and 24 hours, and between 24 and 48 hours, respectively. Change in FB was -82 mL (IQR, -173 to 12 mL) and -107 mL (IQR, -226 to 103) between baseline and 24 hours, and between 24 and 48 hours, respectively. In Bland-Altman analyses, the mean bias between BW and FB at 24 and 48 hours was 54 g (95% CI, 12-97) and -43 g (95% CI, -108 to 23), respectively. This exceeded 1% of the median BW, and limits of agreement ranged from 7.6% to 15% of baseline BW. The precision of paired weight measurements, performed sequentially at each time interval, was high (median difference of ≤1% of BW at each time point). The median weight of connected devices ranged from 2.7% to 3% of BW. There were no episodes of tube or device dislodgments and no change in vasoactive therapies during weight measurements. CONCLUSIONS: There is moderate agreement between the changes in FB and BW, albeit greater than 1% of baseline BW, and the limits of this agreement are wide. Weighing mechanically ventilated infants in intensive care is a relatively safe and precise method for estimating change in fluid status. Device weight represents a relatively large proportion of BW.

Changes in von Willebrand Factor Multimers, Concentration, and Function During Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate changes in von Willebrand factor (VWF) concentration, function, and multimers during pediatric extracorporeal membrane oxygenation (ECMO) and determine whether routine monitoring of VWF during ECMO would be useful in predicting bleeding. DESIGN: Prospective observational study of pediatric ECMO patients from April 2017 to May 2019. SETTING: The PICU in a large, tertiary referral pediatric ECMO center. PATIENTS: Twenty-five neonates and children (< 18 yr) supported by venoarterial ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood samples were collected within 24 hours pre-ECMO, daily for the first 5 days of ECMO, every second day until decannulation, and 24 hours post-ECMO. The STA R Max analyzer was used to measure VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RCo) activity. VWF collagen binding (VWF:CB) was measured using an enzyme-linked immunosorbent assay. VWF multimers were measured using the semi-automated Hydragel 11 VWF Multimer assay. Corresponding clinical data for each patient was also recorded. A total of 25 venoarterial ECMO patients were recruited (median age, 73 d; interquartile range [IQR], 3 d to 1 yr). The median ECMO duration was 4 days (IQR, 3-8 d) and 15 patients had at least one major bleed during ECMO. The percentage of high molecular weight multimers (HMWM) decreased and intermediate molecular weight multimers increased while patients were on ECMO, irrespective of a bleeding status. VWF:Ag increased and the VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios decreased while patients were on ECMO compared with the baseline pre-ECMO samples and healthy children. CONCLUSIONS: Neonates and children on ECMO exhibited a loss of HMWM and lower VWF:CB/VWF:Ag and VWF:RCo/VWF:Ag ratios compared with healthy children, irrespective of major bleeding occurring. Therefore, monitoring VWF during ECMO would not be useful in predicting bleeding in these patients and changes to other hemostatic factors should be investigated to further understand bleeding during ECMO.

Opinion: on the importance of maintaining the functional form of explanatory variables.

In medical research, continuous variables are often categorised into two or more groups before being included in the analysis; this practice often comes with a cost, such as loss of power in analysis, less reliable estimates, and can often leave residual confounding in the results. In this research report, we show this by way of estimates from a regression analysis looking at the association between acute kidney injury and post-operative mortality in a sample of 194 neonates who underwent the Norwood operation. Two models were developed, one using a continuous measure of renal function as the main explanatory variable and second using a categorised version of the same variable. A continuous measure of renal function is more likely to yield reliable estimates and also maintains more statistical power in the analysis to detect a relation between the exposure and outcome. It also reveals the true biological relationship between the exposure and outcome. Categorising a continuous variable may not only miss an important message, it can also get it wrong. Additionally, given a non-linear relationship is commonly encountered between the exposure and outcome variable, investigators are advised to retain a predictor with a linear term only when supported by data. All of this is particularly important in small data sets which account for the majority of clinical research studies.

Platelet Phenotype and Function Changes With Increasing Duration of Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019. SETTING: The PICU in a large tertiary referral pediatric ECMO center. PATIENTS: Eighty-seven neonates and children (< 18 yr) supported by ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood samples were collected on days 1, 2, and 5 of ECMO and were analyzed by whole blood flow cytometry. Corresponding clinical data for each patient was also recorded. A total of 87 patients were recruited (median age, 65 d; interquartile range [IQR], 7 d to 4 yr). The median duration of ECMO was 5 days (IQR, 3-8 d) with a median length of stay in PICU and hospital of 18 days (IQR, 10-29 d) and 35 days (IQR, 19-75 d), respectively. Forty-two patients (48%) had at least one major bleed according to a priori determined definitions, and 12 patients (14%) had at least one thrombotic event during ECMO. Platelet fibrinogen receptor expression decreased (median fluorescence intensity [MFI], 29,256 vs 26,544; p = 0.0005), while von Willebrand Factor expression increased (MFI: 7,620 vs 8,829; p = 0.0459) from day 2 to day 5 of ECMO. Platelet response to agonist, Thrombin Receptor Activator Peptide 6, also decreased from day 2 to day 5 of ECMO, as measured by binding with anti-P-selectin, PAC-1 (binds activated GPIIb/IIIa), and anti-CD63 monoclonal antibodies (P-selectin area under the curve [AUC]: 63.46 vs 42.82, respectively, p = 0.0022; PAC-1 AUC: 93.75 vs 74.46, p = 0.0191; CD63 AUC: 55.69 vs 41.76, p = 0.0020). CONCLUSIONS: The loss of platelet response over time may contribute to bleeding during ECMO. These novel insights may be useful in understanding mechanisms of bleeding in pediatric ECMO and monitoring platelet markers clinically could allow for prediction or early detection of bleeding and thrombosis.

Pragmatic Randomized Trial of Corticosteroids and Inhaled Epinephrine for Bronchiolitis in Children in Intensive Care.

OBJECTIVE: To determine whether the combination of systemic corticosteroids and nebulized epinephrine, compared with standard care, reduces the duration of positive pressure support in children with bronchiolitis admitted to intensive care. STUDY DESIGN: We performed a pragmatic, multicenter, open-label, randomized trial between July 2013 and November 2019 in children younger than 18 months old with a clinical diagnosis of bronchiolitis. The intervention group received the equivalent of 13 mg/kg prednisolone over 3 days, then 1 mg/kg daily for 3 days, plus 0.05 mL/kg of nebulized 1% epinephrine made up to 6 ml with 0.9% saline via jet nebulizer and mask using oxygen at 12 l/min every 30 minutes for 5 doses, then 1-4 hourly for 3 days, then as required for 3 days. The primary outcome was clinician-managed duration of positive pressure support in intensive care defined as high-flow nasal-prong oxygen, nasopharyngeal continuous positive airway pressure, or mechanical ventilation. RESULTS: In total, 210 children received positive pressure support. In the corticosteroid-epinephrine group, 107 children received positive pressure support for a geometric mean of 26 (95% CI, 22-32) hours compared with 40 (95% CI 34-47) hours in 103 controls, adjusted ratio 0.66 (95% CI 0.51-0.84), P = .001. In the intervention group, 41 (38%) children experienced at least 1 adverse event, compared with 39 (38%) in the control group. CONCLUSIONS: In children with severe bronchiolitis, the duration of clinician-managed pressure support was reduced by regular treatment with systemic corticosteroids and inhaled epinephrine compared with standard care. CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Research Network: ACTRN12613000316707.

Fluid Accumulation in Mechanically Ventilated, Critically Ill Children: Retrospective Cohort Study of Prevalence and Outcome.

OBJECTIVES: To describe the prevalence, patterns, explanatory variables, and outcomes associated with fluid accumulation (FA) in mechanically ventilated children. DESIGN: Retrospective cohort study. SETTING: Tertiary PICU. PATIENTS: Children mechanically ventilated for greater than or equal to 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between July 2016 and July 2021, 1,636 children met eligibility criteria. Median age was 5.5 months (interquartile range [IQR], 0.7-46.5 mo), and congenital heart disease was the most common diagnosis. Overall, by day 7 of admission, the median maximum cumulative FA, as a percentage of estimated admission weight, was 7.5% (IQR, 3.3-15.1) occurring at a median of 4 days after admission. Overall, higher FA was associated with greater duration of mechanical ventilation (MV) (mean difference, 1.17 [95% CI, 1.13-1.22]; p < 0.001]), longer intensive care length of stay (LOS) (mean difference, 1.16 [95% CI, 1.12-1.21]; p < 0.001]), longer hospital LOS (mean difference, 1.19 [95% CI, 1.13-1.26]; p < 0.001]), and increased mortality (odds ratio, 1.31 [95% CI, 1.08-1.59]; p = 0.005). However, these associations depended on the effects of children with extreme values, and there was no increase in risk up to 20% FA, overall, in children following cardiopulmonary bypass and in children in the general ICU. When excluding children with maximum FA of >10%, there was no association with duration of MV (mean difference, 0.99 [95% CI, 0.94-1.04]; p = 0.64) and intensive care or hospital LOS (mean difference, 1.01 [95% CI, 0.96-1.06]; p = 0.70 and 1.01 [95% CI, 0.95-1.08]; 0.79, respectively) but an association with reduced mortality 0.71 (95% CI, 0.53-0.97; p = 0.03). CONCLUSIONS: In mechanically ventilated critically ill children, greater maximum FA was associated with longer duration of MV, intensive care LOS, hospital LOS, and mortality. However, these findings were driven by extreme values of FA of greater than 20%, and up to 10%, there was reduced mortality and no signal of harm.

Temperature Management and Health-Related Quality of Life in Children 3 Years After Cardiac Arrest.

OBJECTIVES: Therapeutic hypothermia minimizes neuronal injury in animal models of hypoxic-ischemic encephalopathy with greater effect when used sooner after the insult. Clinical trials generally showed limited benefit but are difficult to perform in a timely manner. In this clinical study, we evaluated the association between the use of hypothermia (or not) and health-related quality of life among survivors of pediatric cardiac arrest as well as overall mortality. DESIGN: Single-center, retrospectively identified cohort with prospective assessment of health-related quality of life. SETTING: PICU of a pediatric hospital. PATIENTS: Children with either out-of-hospital or in-hospital cardiac arrest from January 2012 to December 2017. INTERVENTIONS: Patients were assigned into two groups: those who received therapeutic hypothermia at less than or equal to 35°C and those who did not receive therapeutic hypothermia but who had normothermia targeted (36-36.5°C). The primary outcome was health-related quality of life assessment and the secondary outcome was PICU mortality. MEASUREMENTS AND MAIN RESULTS: We studied 239 children, 112 (47%) in the therapeutic hypothermia group. The median (interquartile range) of lowest temperature reached in the 48 hours post cardiac arrest in the therapeutic hypothermia group was 33°C (32.6-33.6°C) compared with 35.4°C (34.7-36.2°C) in the no therapeutic hypothermia group (p < 0.001). At follow-up, 152 (64%) were alive and health-related quality of life assessments were completed in 128. Use of therapeutic hypothermia was associated with higher lactate and lower pH at baseline. After regression adjustment, therapeutic hypothermia (as opposed to no therapeutic hypothermia) was associated with higher physical (mean difference, 15.8; 95% CI, 3.5-27.9) and psychosocial scores (13.6 [5.8-21.5]). These observations remained even when patients with a temperature greater than 37.5°C were excluded. We failed to find an association between therapeutic hypothermia and lower mortality. CONCLUSIONS: Out-of-hospital or in-hospital cardiac arrest treated with therapeutic hypothermia was associated with higher health-related quality of life scores despite having association with higher lactate and lower pH after resuscitation. We failed to identify an association between use of therapeutic hypothermia and lower mortality.

A Core Outcome Measurement Set for Pediatric Critical Care.

OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

Core-Peripheral Temperature Gradient and Skin Temperature as Predictors of Major Adverse Events Among Postoperative Pediatric Cardiac Patients.

OBJECTIVE: During episodes of low cardiac output, sympathetic neurohumoral responses with peripheral vasoconstriction result in an increase in the core-peripheral temperature gradient (CPTG). However, assessment of CPTG as a surrogate of low cardiac output and a predictor of outcomes in pediatric cardiac patients rarely has been performed. In this retrospective study, the authors assessed the prognostic abilities of CPTG, skin temperature, and serum lactate level for predicting clinical outcomes. DESIGN: A retrospective single-center study. SETTING: Referral high-volume pediatric center. PATIENTS: Patients younger than four months of age with congenital heart disease who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of one or more of the following major adverse events (MAEs) that occurred within seven days after surgery: death from any cause, cardiac arrest, emergency chest reopening, and requirement for extracorporeal membrane oxygenation. A total of 661 patients were included in the study. Univariate logistic regression analyses showed no significant difference in the odds for MAEs with CPTG at admission and at six hours after surgery and in the odds for MAEs with skin temperature at admission. On the other hand, the odds for MAEs increased significantly with increase in serum lactate level at admission (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.26-1.87, p < 0.001) and at six hours after surgery (OR: 1.94, 95% CI: 1.50-2.51, p < 0.001). Areas under the receiver operating curve at admission for predicting MAEs were 0.531 for CPTG, 0.557 for skin temperature, and 0.713 for serum lactate. Multivariate logistic regression analysis showed neither CPTG nor skin temperature at any time point was significantly associated with MAEs. CONCLUSIONS: Both CPTG and skin temperature had low performance for prediction of MAEs in children after cardiac surgery. Either of those markers, especially at admission, should not be used as a single marker for assessing the condition of a patient.

Carboxyhemoglobin levels in children during extracorporeal membrane oxygenation support: a retrospective study.

INTRODUCTION: Hemolysis is a common complication of extracorporeal membrane oxygenation (ECMO). There are few data on whether carboxyhemoglobin (COHb), a potential marker of hemolysis, are elevated during ECMO support. METHODS: We conducted a single-center, retrospective study comparing peak COHb levels of children pre-, during, and post-ECMO from January 2017 to August 2020. RESULTS: There were 154 ECMO runs in 147 children (154 PICU admissions) included in the study. The median age was 3.5 (IQR 0.2, 39.2) months. Veno-arterial ECMO was the predominant mode: 146/154 (94.8%). Eighty-seven children (56.5%) underwent cardiac surgery. Peak COHb levels during ECMO were statistically significantly higher compared to pre ECMO (COHb 1.8% (IQR 1.4, 2.6) vs COHb 1.2% (IQR 0.7, 1.7), p < 0.001) and post ECMO (COHb 1.6% (IQR 1.3, 2.2), p = 0.009). Children with COHb ⩾2% were younger and had longer duration of ECMO support. Plasma hemoglobin weakly correlated with COHb level (r = 0.14; p = 0.04). CONCLUSIONS: Carboxyhemoglobin levels increased during ECMO support compared to the pre and post ECMO period. Younger age and longer ECMO duration were associated with COHb levels ⩾2%. Plasma hemoglobin weakly correlated with COHb level.

Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial.

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.

The natural history of asymptomatic central venous catheter-related thrombosis in critically ill children.

Asymptomatic central venous catheter (CVC)-related thrombosis in children varies in incidence from 5% to 69%. The rate of acute and long-term complications, such as postthrombotic syndrome (PTS), from asymptomatic CVC-related thrombosis is unknown. This article reports the outcomes of a prospective study of 189 children in pediatric intensive care that aimed to determine the frequency of asymptomatic CVC-related thrombosis during hospital admission, and the incidence of residual CVC-related thrombosis and clinically significant PTS 2 years later. Risk factors associated with CVC-related thrombosis were also identified. This study is distinct from previous work as children identified to have asymptomatic CVC-related thrombosis were not treated (clinical team kept blinded) and the entire cohort was followed for 2 years to determine the natural history of asymptomatic thrombosis. Ultrasounds of 146 children determined a 21.9% incidence of acute CVC-related thrombosis. Two children were symptomatic. No radiological thrombosis extension or clinical embolization occurred in the 126 children assessed at follow-up. Using 2 recognized PTS scales, clinically significant PTS was reported in 2 children (1 symptomatic, 1 asymptomatic CVC-related thrombosis), however, neither had functional impairment. Cardiac arrest was a risk factor for CVC-related thrombosis during admission and femoral CVC placement was predictive of residual thrombosis 2 years later. This study challenges the notion that critically ill children with asymptomatic CVC-related thrombosis require anticoagulant treatment, as the results demonstrate that the incidence of acute or long-term complications is low. A larger confirmatory study of nontreatment of CVC-related thrombosis in critically ill children is justified.

Clinical impact of implementing humidified high-flow nasal cannula on interhospital transport among children admitted to a PICU with respiratory distress: a cohort study.

BACKGROUND: There is a limited evidence for humidified high-flow nasal cannula (HHFNC) use on inter-hospital transport. Despite this, its use during transport is increasing in children with respiratory distress worldwide. In 2015 HHFNC was implemented on a specialized pediatric retrieval team serving for Victoria. The aim of this study is to investigate the effect of the HHFNC implementation on the retrieval team on the paediatric intensive care unit (PICU) length of stay and respiratory support use. METHODS: We performed a cohort study using a comparative interrupted time-series approach controlling for patient and temporal covariates, and population-adjusted analysis. We studied 3022 children admitted to a PICU in Victoria with respiratory distress January 2010-December 2019. Patients were divided in pre-intervention era (2010-2014) and post-intervention era (2015-2019). RESULTS: 1006 children following interhospital transport and 2016 non-transport children were included. Median (IQR) age was 1.4 (0.7-4.5) years. Pneumonia (39.1%) and bronchiolitis (34.3%) were common. On retrieval, HHFNC was used in 5.0% (21/420) and 45.9% (269/586) in pre- and post-intervention era. In an unadjusted model, median (IQR) PICU length of stay was 2.2 (1.1-4.2) and 1.7 (0.9-3.2) days in the pre- and post-intervention era in transported children while the figures were 2.4 (1.3-4.9) and 2.1 (1.2-4.5) days in non-transport children. In the multivariable regression model, the intervention was associated with the reduced PICU length of stay (ratio 0.64, 95% confidential interval 0.49-0.83, p = 0.001) with the predicted reduction of PICU length of stay being - 10.6 h (95% confidential interval - 16.9 to - 4.3 h), and decreased respiratory support use (- 25.1 h, 95% confidential interval - 47.9 to - 2.3 h, p = 0.03). Sensitivity analyses including a model excluding less severe children showed similar results. In population-adjusted analyses, respiratory support use decreased from 4837 to 3477 person-hour per year in transported children over the study era, while the reduction was 594 (from 9553 to 8959) person-hour per year in non-transport children. With regard to the safety, there were no escalations of respiratory support mode during interhospital transport. CONCLUSIONS: The implementation of HHFNC on interhospital transport was associated with the reduced PICU length of stay and respiratory support use among PICU admissions with respiratory distress.

Hemodynamic Response to Fluid Boluses for Hypotension in Children in a Cardiac ICU.

OBJECTIVES: To describe the hemodynamic response to fluid boluses for hypotension in children in a cardiac ICU. DESIGN: A prospective, observational study. SETTING: Single-centered cardiac ICU. PATIENTS: Children in a cardiac ICU with hypotension. INTERVENTIONS: Clinician prescribed fluid bolus. MEASUREMENTS AND MAIN RESULTS: Sixty-four fluid boluses were administered to 52 children. Fluid composition was 4% albumin in 36/64 (56%), 0.9% saline in 18/64 (28%), and cardiopulmonary bypass pump blood in 10/64 (16%). The median volume and duration were 5.0 mL/kg (interquartile range, 4.8-5.4) and 8 minutes (interquartile range, 4-19), respectively. Hypovolemia/low filling pressures was the most common additional indication (25/102 [25%]). Mean arterial pressure response, defined as a 10% increase from baseline, occurred in 42/64 (66%) of all fluid boluses at a median time of 6 minutes (interquartile range, 4-11). Mean arterial pressure responders had a median peak increase in the mean arterial pressure of 15 mm Hg (43 mm Hg [interquartile range, 29-50 mm Hg] to 58 mm Hg [interquartile range, 49-65 mm Hg]) at 17 minutes (interquartile range, 14-24 min) compared with 4 mm Hg (48 mm Hg [interquartile range, 40-51 mm Hg] to 52 mm Hg [interquartile range, 45-56 mm Hg]) at 10 minutes (interquartile range, 3-18 min) in nonresponders. Dissipation of mean arterial pressure response, when defined as a subsequent decrement in mean arterial pressure below 10%, 5%, and 2% increases from baseline, occurred in 28/42 (67%), 18/42 (43%), and 13/42 (31%) of mean arterial pressure responders, respectively. Cardiopulmonary bypass pump blood was strongly associated with peak change in mean arterial pressure from baseline (coefficient 11.0 [95% CI, 4.3-17.7]; p = 0.02). Fifty out of 64 (78%) were receiving a vasoactive agent. However, change in vasoactive inotrope score was not associated with change in mean arterial pressure (coefficient 2.3 [95% CI, -2.5 to -7.2]; p = 0.35). Timing from admission, nor fluid bolus duration, influenced mean arterial pressure response. CONCLUSIONS: In children with hypotension in a cardiac ICU, the median dose and duration of fluid boluses were 5 mL/kg and 8 minutes. Peak response occurred shortly following administration and commonly returned to baseline.

Recurrent Extubation Failure Following Neonatal Cardiac Surgery Is Associated with Increased Mortality.

Extubation failure (EF) following neonatal cardiac surgery is associated with increased mortality. Neonates who experienced EF twice or more (recurrent EF) may have worse outcomes than those who have a single EF or no-EF. The aims of this study are to investigate the in hospital mortality for neonates with recurrent EF compared to those with single or no-EF, and determine factors associated with recurrent EF. Neonates' ≤ 28 days who underwent cardiac surgery from January 2008 to December 2019 were included. EF was defined as unplanned reintubation within 72 h after a planned extubation. 1187 (18 recurrent EF, 84 single EF and 1085 no-EF) neonates were included. Recurrent EF occurred in 18 (17.6%) of 102 neonates undergoing a second extubation. The median time (IQR) to reintubation after the first and second extubations were similar, being 20.9 (3.3-45.2) versus 19.4 (5.5-47) h. The reason for a second-time EF was respiratory in 39% and cardiovascular in 33%. Recurrent EF and single EF was associated with increased mortality (odds ratio, 95% confidence interval (CI) 23.5, 6.9-79.9) and (odds ratio, 95% CI 5.2, 2.3-12.0) compared to no-EF. Based on the final model with risk adjustment, predicted mortality was 29.0% in recurrent EF, 6.5% in single EF, and 1.2% in no-EF. First-time EF due to cardiovascular compromise was associated with recurrent EF (odds ratio, 95% CI 3.1, 1.0-9.7). This study confirmed that patients with recurrent EF have a high morality. Neonates with a cardiovascular reason for first-time EF are more likely to have a recurrent EF than those with other causes.

COVID-19: A new challenge for ECMO.

COVID results in a variety of pathophysiology that causes cardiorespiratory and the need for ECMO. These include hypoxic respiratory failure, cardiogenic shock, cardiac arrest, multisystem inflammatory disease, and vascular thrombosis with pulmonary embolism. A variety of cannulation strategies are required and the "hyperinflammation" and consequent coagulation abnormalities mandate new strategies to provide optimal ECMO support.

Milrinone Acts as a Vasodilator But Not an Inotrope in Children After Cardiac Surgery-Insights From Wave Intensity Analysis.

OBJECTIVES: Milrinone is an inodilator widely used in the postoperative management of children undergoing cardiac surgery. The literature supporting its inotropic effect is sparse. We sought to study the effect of milrinone on the vasculature and its effects on the ventricular function using wave intensity analysis. We also intended to evaluate the feasibility of using wave intensity analysis by the bedside. DESIGN: prospective single-center observational study. SETTING: PICU of a tertiary children's hospital. PATIENTS: Children (< 18 yr) admitted to PICU following cardiac surgery who required to be commenced on a milrinone infusion. INTERVENTIONS: Echocardiography and Doppler ultrasound assessments for wave intensity analysis were performed prior to commencing milrinone and 4-6 hours after milrinone infusion. MEASUREMENTS AND MAIN RESULTS: Wave intensity analysis was successfully performed and analyzed in 15 of 16 patients (94%). We identified three waves-a forward compression wave, backward compression wave, and forward decompression wave. The waves were described with their cumulative intensity and wave-related pressure change. There was a 26% reduction in backward compression wave cumulative intensity following the introduction of milrinone. Other variables (backward compression wave cumulative intensity/forward compression wave cumulative intensity ratio, backward compression wave wave-related pressure change, backward compression wave wave-related pressure change/forward compression wave wave-related pressure change ratio) consistent with vasodilation also decreased after milrinone. It also decreased the vascular wavespeed by 7.1% and increased the distensibility of the vessels by 14.6%. However, it did not increase forward compression wave cumulative intensity, a variable indicating the systolic force generated by the ventricle. Forward decompression wave cumulative intensity indicating ventricular early diastolic relaxation also did not change. CONCLUSIONS: In a cohort of children recovering in PICU after having undergone cardiac surgery, we found that milrinone acted as a vasodilator but did not demonstrate an improvement in the contractility or an improved relaxation of the left ventricle as assessed by wave intensity analysis. We were able to demonstrate the feasibility and utility of wave intensity analysis to further understand ventriculo-vascular interactions in an intensive care setting.

Gestational Age and Risk of Mortality in Term-Born Critically Ill Neonates Admitted to PICUs in Australia and New Zealand.

OBJECTIVES: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (≥ 37 wk') admitted to PICUs in Australia and New Zealand. DESIGN: Observational multicenter cohort study. SETTING: PICUs in Australia and New Zealand. PATIENTS: Term-born neonates (≥ 37 wk) admitted to PICUs. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS:: We studied 5,073 infants born with a gestational age greater than or equal to 37 weeks and were less than 28 days old when admitted to a PICU in Australia or New Zealand between 2007 and 2016. The association between gestational age and mortality was estimated using a multivariable logistic regression model, adjusting for age, sex, indigenous status, Pediatric Index of Mortality version 2, and site. The median gestational age was 39.1 weeks (interquartile range, 38.2-40 wk) and mortality in hospital was 6.6%. Risk of mortality declined log-linearly with gestational age. The adjusted analysis showed a 20% (95% CI, 11-28%) relative reduction in mortality for each extra week of gestation beyond 37 weeks. The effect of gestation was stronger among those who received extracorporeal life support: each extra week of gestation was associated with a 44% (95% CI, 25-57%) relative reduction in mortality. Longer gestation was also associated with reduced length of stay in hospital: each week increase in gestation, the average length of stay decreased by 4% (95% CI, 2-6%). CONCLUSIONS: Among neonates born at "term" who are admitted to a PICU, increasing gestational age at birth is associated with a substantial reduction in the risk of dying in hospital. The maturational influence on outcome was more strongly noted in the sickest neonates, such as those requiring extracorporeal life support. This information is important in view of the increasing proportion of planned births in both high- and low-/middle-income countries.

A Core Outcome Set for Pediatric Critical Care.

OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.