Thirty years of ANZICS CORE: A clinical quality success story.

In 2023, the Australian and New Zealand Intensive Care Society (ANZICS) Registry run by the Centre for Outcomes and Resources Evaluation (CORE) turns 30 years old. It began with the Adult Patient Database, the Australian and New Zealand Paediatric Intensive Care Registry, and the Critical Care Resources Registry, and it now includes Central Line Associated Bloodstream Infections Registry, the Extra-Corporeal Membrane Oxygenation Database, and the Critical Health Resources Information System. The ANZICS Registry provides comparative case-mix reports, risk-adjusted clinical outcomes, process measures, and quality of care indicators to over 200 intensive care units describing more than 200 000 adult and paediatric admissions annually. The ANZICS CORE outlier management program has been a major contributor to the improved patient outcomes and provided significant cost savings to the healthcare sector. Over 200 peer-reviewed papers have been published using ANZICS Registry data. The ANZICS Registry was a vital source of information during the COVID-19 pandemic. Upcoming developments include reporting of long-term survival and patient-reported outcome and experience measures.

Potential benefits of prenatal diagnosis of TGA in Australia may be outweighed by the adverse effects of earlier delivery: likely causation and potential solutions.

OBJECTIVE: Prenatal 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. METHODS: Cohort 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. RESULTS: Gestational 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. CONCLUSION: Among 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.

Machine learning to predict poor school performance in paediatric survivors of intensive care: a population-based cohort study.

PURPOSE: Whilst survival in paediatric critical care has improved, clinicians lack tools capable of predicting long-term outcomes. We developed a machine learning model to predict poor school outcomes in children surviving intensive care unit (ICU). METHODS: Population-based study of children < 16 years requiring ICU admission in Queensland, Australia, between 1997 and 2019. Failure to meet the National Minimum Standard (NMS) in the National Assessment Program-Literacy and Numeracy (NAPLAN) assessment during primary and secondary school was the primary outcome. Routine ICU information was used to train machine learning classifiers. Models were trained, validated and tested using stratified nested cross-validation. RESULTS: 13,957 childhood ICU survivors with 37,200 corresponding NAPLAN tests after a median follow-up duration of 6 years were included. 14.7%, 17%, 15.6% and 16.6% failed to meet NMS in school grades 3, 5, 7 and 9. The model demonstrated an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.8 (standard deviation SD, 0.01), with 51% specificity to reach 85% sensitivity [relative Area Under the Precision Recall Curve (rel-AUPRC) 3.42, SD 0.06]. Socio-economic status, illness severity, and neurological, congenital, and genetic disorders contributed most to the predictions. In children with no comorbidities admitted between 2009 and 2019, the model achieved a AUROC of 0.77 (SD 0.03) and a rel-AUPRC of 3.31 (SD 0.42). CONCLUSIONS: A machine learning model using data available at time of ICU discharge predicted failure to meet minimum educational requirements at school age. Implementation of this prediction tool could assist in prioritizing patients for follow-up and targeting of rehabilitative measures.

Trends in Childhood Oncology Admissions to ICUs in Australia and New Zealand.

OBJECTIVES: There are few robust, national-level reports of contemporary trends in pediatric oncology admissions, resource use, and mortality. We aimed to describe national-level data on trends in intensive care admissions, interventions, and survival for children with cancer. DESIGN: Cohort study using a binational pediatric intensive care registry. SETTING: Australia and New Zealand. PATIENTS: Patients younger than 16 years, admitted to an ICU in Australia or New Zealand with an oncology diagnosis between January 1, 2003, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined trends in oncology admissions, ICU interventions, and both crude and risk-adjusted patient-level mortality. Eight thousand four hundred ninety admissions were identified for 5,747 patients, accounting for 5.8% of PICU admissions. Absolute and population-indexed oncology admissions increased from 2003 to 2018, and median length of stay increased from 23.2 hours (interquartile range [IQR], 16.8-62 hr) to 38.8 hours (IQR, 20.9-81.1 hr) ( p < 0.001). Three hundred fifty-seven of 5,747 patients died (6.2%). There was a 45% reduction in risk-adjusted ICU mortality, which reduced from 3.3% (95% CI, 2.1-4.4) in 2003-2004 to 1.8% (95% CI, 1.1-2.5%) in 2017-2018 ( p trend = 0.02). The greatest reduction in mortality seen in hematological cancers and in nonelective admissions. Mechanical ventilation rates were unchanged from 2003 to 2018, while the use of high-flow nasal prong oxygen increased (incidence rate ratio, 2.43; 95% CI, 1.61-3.67 per 2 yr). CONCLUSIONS: In Australian and New Zealand PICUs, pediatric oncology admissions are increasing steadily and such admissions are staying longer, representing a considerable proportion of ICU activity. The mortality of children with cancer who are admitted to ICU is low and falling.

Quality measurement and surveillance platforms in critically ill children: A scoping review.

BACKGROUND/AIM: The objective of this study was to describe current surveillance platforms which support routine quality measurement in paediatric critical care. METHOD: Scoping review. The search strategy consisted of a traditional database and grey literature search as well as expert consultation. Surveillance platforms were eligible for inclusion if they collected measures of quality in critically ill children. RESULTS: The search strategy identified 21 surveillance platforms, collecting 57 unique outcome (70%), process (23%), and structural (7%) quality measures. Hospital-associated infections were the most commonly collected outcome measure across all platforms (n = 11; 52%). In general, case definitions were not harmonised across platforms, with the exception of nationally mandated hospital-associated infections (e.g., central line-associated blood stream infection). Data collection relied on manual coding. Platforms typically did not provide an evidence-based rationale for measures collected, with no identifiable reports of co-designed, consensus-derived measures or consumer involvement in measure selection or prioritisation. CONCLUSIONS: Quality measurement in critically ill children lacks uniformity in definition which limits local and international benchmarking. Current surveillance activities for critically ill children focus heavily on outcome measurement, with process, structural, and patient-reported measures largely overlooked. Long-term outcome measures were not routinely collected. Harmonisation of paediatric intensive care unit quality measures is needed and can be achieved using prioritisation and consensus/co-design methods.

Association Between Centralization and Outcome for Children Admitted to Intensive Care in Australia and New Zealand: A Population-Based Cohort Study.

OBJECTIVES: To describe regional differences and change over time in the degree of centralization of pediatric intensive care in Australia and New Zealand (ANZ) and to compare the characteristics and ICU mortality of children admitted to specialist PICUs and general ICUs (GICUs). DESIGN: A retrospective cohort study using registry data for two epochs of ICU admissions, 2003-2005 and 2016-2018. SETTING: Population-based study in ANZ. PATIENTS: A total of 43,256 admissions of children aged younger than 16 years admitted to an ICU in ANZ were included. Infants aged younger than 28 days without cardiac conditions were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was risk-adjusted ICU mortality. Logistic regression was used to investigate the association of mortality with the exposure to ICU type, epoch, and their interaction. Compared with children admitted to GICUs, children admitted to PICUs were younger (median 25 vs 47 mo; p < 0.01) and stayed longer in ICU (median 1.6 vs 1.0 d; p < 0.01). For the study overall, 93% of admissions in Australia were to PICUs whereas in New Zealand only 63% of admissions were to PICUs. The adjusted odds of death in epoch 2 relative to epoch 1 decreased (adjusted odds ratio [AOR], 0.50; 95% CI, 0.42-0.59). There was an interaction between unit type and epoch with increased odds of death associated with care in a GICU in epoch 2 (AOR, 1.63; 95% CI, 1.05-2.53 for all admissions; 1.73, CI, 1.002-3.00 for high-risk admissions). CONCLUSIONS: Risk-adjusted mortality of children admitted to specialist PICUs decreased over a study period of 14 years; however, a similar association between time and outcome was not observed in high-risk children admitted to GICUs. The results support the continued use of a centralized model of delivering intensive care for critically ill children.

Early Peritoneal Dialysis and Postoperative Outcomes in Infants After Pediatric Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: Peritoneal dialysis (PD) is used in several cardiac surgical units after cardiac surgery, and early initiation of PD after surgery may have the potential to influence postoperative outcomes. This systematic review and meta-analysis aims to summarize the evidence for the association between early PD after cardiac surgery and postoperative outcomes. DATA SOURCES: MEDLINE, Embase, and PubMed from 1981 to November 1, 2021. STUDY SELECTION: Observational studies and randomized trials reporting on early PD after pediatric cardiac surgery. DATA EXTRACTION: Random-effects meta-analysis was used to estimate the pooled odds ratios (ORs) and their 95% CIs for postoperative mortality and pooled mean difference (MD) (95% CI) for duration of mechanical ventilation and ICU length of stay. DATA SYNTHESIS: We identified nine studies from the systematic review, and five were considered suitable for meta-analysis. Early initiation of PD after cardiac surgery was associated with a reduction in postoperative mortality (OR, 0.43 (95% CI, 0.23-0.80); number of estimates = 4). Early commencement of PD shortened duration of mechanical ventilation (MD [95% CI], -1.09 d [-1.86 to -0.33 d]; I2 = 56.1%; p = 0.06) and intensive care length of stay (MD [95% CI], -2.46 d [-3.57 to -1.35 d]; I2 = 18.7%; p = 0.30], respectively. All three estimates had broad 95% prediction intervals (crossing null) denoting major heterogeneity between studies and wide range of possible study estimates in similar future studies. Overall, studies reporting on the effects of early PD included only a subset of infants undergoing cardiac surgery (typically high-risk infants), so selection bias may be a major issue in published studies. CONCLUSIONS: This review suggests that early initiation of PD may be associated with beneficial postoperative outcomes in infants after cardiac surgery. However, these results were based on studies of varying qualities and risk of bias. Early identification of high-risk infants after cardiac surgery is important so that prevention or early mitigation strategies can be applied to this cohort. Future prospective studies in high-risk populations are needed to study the role of early PD in influencing postoperative outcomes.

Admissions of Children and Adolescents With Deliberate Self-harm to Intensive Care During the SARS-CoV-2 Outbreak in Australia.

Importance: Identification of potential indirect outcomes associated with the COVID-19 pandemic in the pediatric population may be essential for understanding the challenges of the current global public health crisis for children and adolescents. Objective: To investigate whether the SARS-CoV-2 outbreak and subsequent effective public health measures in Australia were associated with an increase in admissions to intensive care units (ICUs) of children and adolescents with deliberate self-harm (DSH). Design, Setting, and Participants: This national, multicenter cohort study was conducted using the Australian data subset of the binational Australian and New Zealand Paediatric Intensive Care registry, a collaborative containing more than 200 000 medical records with continuous contributions from all 8 Australian specialist, university-affiliated pediatric ICUs, along with 1 combined neonatal-pediatric ICU and 14 general (adult) ICUs in Australia. The study period encompassed 6.5 years from January 1, 2015, to June 30, 2021. Patients aged 12 to 17 years were included. Data were analyzed from December 2021 through February 2022. Exposures: Any of the following admission diagnoses: ingestion of a drug, ingestion of a nondrug, hanging or strangulation, or self-injury. Main Outcomes and Measures: The primary outcome measure was the temporal trend for national incidence of DSH ICU admissions per 1 million children and adolescents aged 12 to 17 years in Australia. Results: A total of 813 children and adolescents aged 12 to 17 years admitted to ICUs with DSH were identified among 64 145 patients aged 0 to 17 years in the Australian subset of the registry during the study period. Median (IQR) age was 15.1 (14.3-15.8) years; there were 550 (67.7%) female patients, 261 (32.2%) male patients, and 2 (0.2%) patients with indeterminate sex. At the onset of the pandemic, monthly incidence of DSH ICU admissions per million children and adolescents increased from 7.2 admissions in March 2020 to a peak of 11.4 admissions by August 2020, constituting a significant break in the temporal trend (odds ratio of DSH ICU admissions on or after vs before March 2020, 4.84; 95% CI, 1.09 to 21.53; P = .04). This occurred while the rate of all-cause admissions to pediatric ICUs of children and adolescents of all ages (ie, ages 0-17 years) per 1 million children and adolescents decreased from a long-term monthly median (IQR) of 150.9 (138.1-159.8) admissions to 91.7 admissions in April 2020. Conclusions and Relevance: This cohort study found that the coronavirus pandemic in Australia was associated with a significant increase in admissions of children and adolescents to intensive care with DSH.

Educational Outcomes of Childhood Survivors of Critical Illness-A Population-Based Linkage Study.

OBJECTIVES: Major postintensive care sequelae affect up to one in three adult survivors of critical illness. Large cohorts on educational outcomes after pediatric intensive care are lacking. We assessed primary school educational outcomes in a statewide cohort of children who survived PICU during childhood. DESIGN: Multicenter population-based study on children less than 5 years admitted to PICU. Using the National Assessment Program-Literacy and Numeracy database, the primary outcome was educational achievement below the National Minimum Standard (NMS) in year 3 of primary school. Cases were compared with controls matched for calendar year, grade, birth cohort, sex, socioeconomic status, Aboriginal and Torres Strait Islander status, and school. Multivariable logistic regression models to predict educational outcomes were derived. SETTING: Tertiary PICUs and mixed ICUs in Queensland, Australia. PATIENTS: Children less than 5 years admitted to PICU between 1998 and 2016. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Year 3 primary school data were available for 5,017 PICU survivors (median age, 8.0 mo at first PICU admission; interquartile range, 1.9-25.2). PICU survivors scored significantly lower than controls across each domain (p < 0.001); 14.03% of PICU survivors did not meet the NMS compared with 8.96% of matched controls (p < 0.001). In multivariate analyses, socioeconomic status (odds ratio, 2.14; 95% CI, 1.67-2.74), weight (0.94; 0.90-0.97), logit of Pediatric Index of Mortality-2 score (1.11; 1.03-1.19), presence of a syndrome (11.58; 8.87-15.11), prematurity (1.54; 1.09-2.19), chronic neurologic conditions (4.38; 3.27-5.87), chronic respiratory conditions (1.65; 1.24-2.19), and continuous renal replacement therapy (4.20; 1.40-12.55) were independently associated with a higher risk of not meeting the NMS. CONCLUSIONS: In this population-based study of childhood PICU survivors, 14.03% did not meet NMSs in the standardized primary school assessment. Socioeconomic status, underlying diseases, and severity on presentation allow risk-stratification to identify children most likely to benefit from individual follow-up and support.

Study protocol and statistical analysis plan for the Early Peritoneal Dialysis in Infants after Cardiac Surgery (EPICS) trial.

Background: Peritoneal dialysis (PD) is a commonly used therapy after infant cardiac surgery. It is unclear whether early PD commenced soon after admission to an intensive care unit (ICU) after cardiac surgery results in better outcomes. Objective: To describe the study protocol and statistical analysis plan for the Early Peritoneal Dialysis in Infants after Cardiac Surgery (EPICS) trial. Design, setting, participants and intervention: The EPICS trial is an open, randomised, two-group, single-centre clinical study of infants ≤ 180 days of age who had cardiac surgery (in Risk-Adjusted Classification for Congenital Heart Surgery version 1 categories 3-6) with cardiopulmonary bypass. Participants will be randomly assigned 1:1 to early PD (treatment group) or no early PD (control group). Those assigned to the treatment group will begin receiving PD soon after ICU admission and continue receiving it for 24 hours. Those in the control group will not receive PD during the first 24 hours. Main outcome measures: The primary outcome is a composite measure consisting of one or more of death, cardiac arrest, emergency chest reopening, and requirement for extracorporeal membrane oxygenation (ECMO) within 90 days. The main secondary outcomes are duration of mechanical ventilation, ICU length of stay, hospital length of stay, vasoactive-inotropic score at 24 hours, and cumulative per cent fluid balance by end of Day 2. At Day 90, events such as mortality, requirement for ECMO, cardiac arrest, chest reopening, volume of packed red blood cell transfusion, postoperative infection, readmission to ICU, renal injury and brain injury will be assessed. Conclusions: The EPICS trial aims to evaluate the role of early PD after infant cardiac surgery in lowering the rate of a composite major outcome. In addition, it will test the effect of early PD on duration of mechanical ventilation, and on ICU and hospital length of stay. Trial registration: ACTRN12617001614381.

Increasing ICU capacity to accommodate higher demand during the COVID-19 pandemic.

OBJECTIVES: To describe the short term ability of Australian intensive care units (ICUs) to increase capacity in response to heightened demand caused by the COVID-19 pandemic. DESIGN: Survey of ICU directors or delegated senior clinicians (disseminated 30 August 2021), supplemented by Australian and New Zealand Intensive Care Society (ANZICS) registry data. SETTING: All 194 public and private Australian ICUs. MAIN OUTCOME MEASURES: Numbers of currently available and potentially available ICU beds in case of a surge; available levels of ICU-relevant equipment and staff. RESULTS: All 194 ICUs responded to the survey. The total number of currently open staffed ICU beds was 2183. This was 195 fewer (8.2%) than in 2020; the decline was greater for rural/regional (18%) and private ICUs (18%). The reported maximal ICU bed capacity (5623) included 813 additional physical ICU bed spaces and 2627 in surge areas outside ICUs. The number of available ventilators (7196) exceeded the maximum number of ICU beds. The reported number of available additional nursing staff would facilitate the immediate opening of 383 additional physical ICU beds (47%), but not the additional bed spaces outside ICUs. CONCLUSIONS: The number of currently available staffed ICU beds is lower than in 2020. Equipment shortfalls have been remediated, with sufficient ventilators to equip every ICU bed. ICU capacity can be increased in response to demand, but is constrained by the availability of appropriately trained staff. Fewer than half the potentially additional physical ICU beds could be opened with currently available staff numbers while maintaining pre-pandemic models of care.

Priorities for paediatric critical care research: a modified Delphi study by the Australian and New Zealand Intensive Care Society Paediatric Study Group.

Objective: Most interventions in paediatric critical care lack high grade evidence. We aimed to identify the key research priorities and key clinical outcome measures pertinent to research in paediatric intensive care patients. Design: Modified three-stage Delphi study combining staged online surveys, followed by a face-to-face discussion and final voting. Setting: Paediatric intensive care units in Australia and New Zealand. Participants: Medical and nursing staff working in intensive care. Main outcome measurements: Self-reported priorities for research. Results: 193 respondents provided a total of 267 research questions and 234 outcomes. In Stage 3, the top 56 research questions and 50 outcomes were discussed face to face, which allowed the identification of the top 20 research questions with the Hanlon prioritisation score and the top 20 outcomes. Topics centred on the use of intravenous fluids (restrictive v liberal fluids, use of fluid resuscitation bolus, early inotrope use, type of intravenous fluid, and assessment of fluid responsiveness), and patient- and family-centred outcomes (health-related quality of life, liberation) emerged as priorities. While mortality, length of stay, and organ support/organ dysfunction were considered important and the most feasible outcomes, long term quality of life and neurodevelopmental measures were rated highly in terms of their importance. Conclusions: Using a modified Delphi method, this study provides guidance towards prioritisation of research topics in paediatric critical care in Australia and New Zealand, and identifies study outcomes of key relevance to clinicians and experts in the field.

Role of levosimendan in weaning children requiring veno-arterial extracorporeal membrane oxygenation after cardiac surgery.

OBJECTIVES: Levosimendan use is associated with more successful decannulation from veno-arterial extracorporeal membrane oxygenation (VA ECMO) in adults. We sought to determine the role of levosimendan in children who required VA ECMO after cardiac surgery. METHODS: This observational study compares the outcomes of children who required VA ECMO after cardiac surgery and received levosimendan for weaning with those who did not receive the drug. A doubly robust estimation methodology (inverse probability of treatment weighting with regression adjustment) was used to balance study covariates (age, weight, sex, lactate pre-ECMO, vasoactive-inotropic score pre-ECMO, ECMO indication, ECMO modality, Risk Adjustment for Congenital Heart Surgery-1 category), and the final model was further adjusted for duration of ECMO. RESULTS: Between January 2012 and December 2018, 118 eligible children received 145 ECMO runs [failed weaning from cardiopulmonary bypass, 67/145 (46%); low cardiac output state, 30/145 (21%); extracorporeal cardiopulmonary resuscitation, 47/145 (32%); other reasons in 1]. Levosimendan was administered before decannulation in 54/145 (37%) runs. The median time to start levosimendan after ECMO cannulation was 39 h (interquartile range, 14-83 h). The unadjusted rates of weaning failure in the levosimendan vs control group were 7% (4/54) vs 19% (17/91). In the controlled analysis, levosimendan was associated with decreased risk of weaning failure [adjusted relative risk (95% confidence interval), 0.20 (0.07-0.57)] and decreased risk of in-hospital mortality [adjusted relative risk (95% confidence interval), 0.45 (0.26-0.76)]. CONCLUSIONS: Levosimendan administration in children requiring VA ECMO after cardiac surgery was associated with decreased risk of weaning failure and decreased in-hospital mortality.

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.

Dexmedetomidine Sedation in Mechanically Ventilated Critically Ill Children: A Pilot Randomized Controlled Trial.

OBJECTIVES: To assess the feasibility, safety, and efficacy of a sedation protocol using dexmedetomidine as the primary sedative in mechanically ventilated critically ill children. DESIGN: Open-label, pilot, prospective, multicenter, randomized, controlled trial. The primary outcome was the proportion of sedation scores in the target sedation range in the first 48 hours. Safety outcomes included device removal, adverse events, and vasopressor use. Feasibility outcomes included time to randomization and protocol fidelity. SETTING: Six tertiary PICUs in Australia and New Zealand. PATIENTS: Critically ill children, younger than 16 years old, requiring intubation and mechanical ventilation and expected to be mechanically ventilated for at least 24 hours. INTERVENTIONS: Children randomized to dexmedetomidine received a dexmedetomidine-based algorithm targeted to light sedation (State Behavioral Scale -1 to +1). Children randomized to usual care received sedation as determined by the treating clinician (but not dexmedetomidine), also targeted to light sedation. MEASUREMENTS AND MAIN RESULTS: Sedation with dexmedetomidine as the primary sedative resulted in a greater proportion of sedation measurements in the light sedation range (State Behavioral Scale -1 to +1) over the first 48 hours (229/325 [71%] vs 181/331 [58%]; p = 0.04) and the first 24 hours (66/103 [64%] vs 48/116 [41%]; p < 0.001) compared with usual care. Cumulative midazolam dosage was significantly reduced in the dexmedetomidine arm compared with usual care (p = 0.002).There were more episodes of hypotension and bradycardia with dexmedetomidine (including one serious adverse event) but no difference in vasopressor requirements. Median time to randomization after intubation was 6.0 hours (interquartile range, 2.0-9.0 hr) in the dexmedetomidine arm compared with 3.0 hours (interquartile range, 1.0-7.0 hr) in the usual care arm (p = 0.24). CONCLUSIONS: A sedation protocol using dexmedetomidine as the primary sedative was feasible, appeared safe, achieved early, light sedation, and reduced midazolam requirements. The findings of this pilot study justify further studies of sedative agents in critically ill children.

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.

Surge capacity of intensive care units in case of acute increase in demand caused by COVID-19 in Australia.

OBJECTIVES: To assess the capacity of intensive care units (ICUs) in Australia to respond to the expected increase in demand associated with COVID-19. DESIGN: Analysis of Australian and New Zealand Intensive Care Society (ANZICS) registry data, supplemented by an ICU surge capability survey and veterinary facilities survey (both March 2020). SETTINGS: All Australian ICUs and veterinary facilities. MAIN OUTCOME MEASURES: Baseline numbers of ICU beds, ventilators, dialysis machines, extracorporeal membrane oxygenation machines, intravenous infusion pumps, and staff (senior medical staff, registered nurses); incremental capability to increase capacity (surge) by increasing ICU bed numbers; ventilator-to-bed ratios; number of ventilators in veterinary facilities. RESULTS: The 191 ICUs in Australia provide 2378 intensive care beds during baseline activity (9.3 ICU beds per 100 000 population). Of the 175 ICUs that responded to the surge survey (with 2228 intensive care beds), a maximal surge would add an additional 4258 intensive care beds (191% increase) and 2631 invasive ventilators (120% increase). This surge would require additional staffing of as many as 4092 senior doctors (245% increase over baseline) and 42 720 registered ICU nurses (269% increase over baseline). An additional 188 ventilators are available in veterinary facilities, including 179 human model ventilators. CONCLUSIONS: The directors of Australian ICUs report that intensive care bed capacity could be near tripled in response to the expected increase in demand caused by COVID-19. But maximal surge in bed numbers could be hampered by a shortfall in invasive ventilators and would also require a large increase in clinician and nursing staff numbers.

The Effect of Imputation of PaO2/FIO2 From SpO2/FIO2 on the Performance of the Pediatric Index of Mortality 3.

OBJECTIVES: To investigate if the performance of Pediatric Index of Mortality 3 is improved by including imputed values for the PaO2/FIO2 ratio where measurements of PaO2 or FIO2 are missing. DESIGN: A prospective observational study. SETTING: A bi-national pediatric intensive care registry. PATIENTS: The records of 37,983 admissions of children less than 16 years old admitted to 19 ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seven published equations describing an association between PaO2/FIO2 and oxygen saturation measured by pulse oximetry (SpO2)/FIO2 were used to derive an alternative variable d100 × FIO2/PaO2 for the Pediatric Index of Mortality 3 variable 100 × FIO2/PaO2. Six equations exclude SpO2/FIO2 values if SpO2 is greater than 96-98%. 100 × FIO2/PaO2 was missing in 72% of patient records primarily due to missing PaO2, d100 × FIO2/PaO2 was missing in 71% of patient records if values of SpO2greater than 97% were excluded or in 17% of patient records if all measurements of SpO2 were included. Univariable analysis supported the inclusion of SpO2 values greater than 97%. Compared to the standard Pediatric Index of Mortality 3 model, two alternative models imputing 100 × FIO2/PaO2 from d100 × FIO2/PaO2 only if 100 × FIO2/PaO2 was missing, or using d100 × FIO2/PaO2 values exclusively, resulted in a small but statistically significant improvements in discrimination of Pediatric Index of Mortality 3 (area under the receiver operator curve 0.9068 [0. 8965-0. 9171]; 0.9083 [0.8981-0.9184]; 0.9087 [0.8987-0.9188], respectively). CONCLUSIONS: Imputation of the PaO2/FIO2 ratio in cases where arterial sampling was not performed resulted in a large reduction in the rate of missing data if all values of SpO2 were included. The imputation technique improved the discrimination of Pediatric Index of Mortality 3; however, the magnitude of the increment in overall model performance was small. A possible benefit of the approach is reducing the potential for bias resulting from variation in practice for invasive monitoring of oxygenation.

Peak Creatinine, Cardiopulmonary Bypass, and Mortality After Stage 1 Single-Ventricle Reconstruction.

BACKGROUND: Serum creatinine is the most commonly used marker to diagnose acute kidney injury. Studies exploring creatinine patterns in the single-ventricle population are scarce. We studied serum creatinine up to 5 postoperative days after the stage 1 operation and assessed its relationship with outcomes. METHODS: Neonates who underwent a first-stage single-ventricle operation (Norwood or a Damus-Kaye-Stansel) between 2005 and 2017 were retrospectively analyzed. Peak percentage creatinine change (PPCC) was defined as the difference between the baseline (preoperative) and the peak postoperative level (within 5 postoperative days), expressed as a percentage of the baseline level. RESULTS: Among 187 neonates included, the median PPCC was 38.7% (interquartile range, 14.1%-73.1%), and in-hospital mortality was 17% (31 of 187). A controlled analysis showed that for every 10-minute increase in cardiopulmonary bypass duration (CPB), the PPCC increased by 1.8% (95% confidence interval [CI], 0.7%-2.9%; P = .002). Risk of in-hospital death increased log-linearly with PPCC. The adjusted odds ratios for death in the hospital associated with a 50%, 100%, and 200%, increase in peak percentage creatinine change were 1.85 (95% CI, 1.23-2.78), 3.41 (95% CI, 1.15-7.72), and 11.66 (95% CI, 2.28-59.63), respectively. In-hospital death was also associated with CPB duration (adjusted odds ratio, 1.13 per 10-minute increase; 95% CI, 1.05-1.22; P = .001). CONCLUSIONS: Increase in CPB duration has a strong linear association with increase in PPCC after stage 1 single-ventricle reconstruction. Increase in PPCC and CPB duration has a strong linear association with hospital mortality. It is important to identify therapies that minimize complications associated with prolonged CPB duration in high-risk populations.

Epidemiology of childhood death in Australian and New Zealand intensive care units.

PURPOSE: Data on childhood intensive care unit (ICU) deaths are needed to identify changing patterns of intensive care resource utilization. We sought to determine the epidemiology and mode of pediatric ICU deaths in Australia and New Zealand (ANZ). METHODS: This was a retrospective, descriptive study of multicenter data from pediatric and mixed ICUs reported to the ANZ Pediatric Intensive Care Registry and binational Government census. All patients < 16 years admitted to an ICU between 1 January 2006 and 31 December 2016 were included. Primary outcome was ICU mortality. Subject characteristics and trends over time were evaluated. RESULTS: Of 103,367 ICU admissions, there were 2672 (2.6%) deaths, with 87.6% of deaths occurring in specialized pediatric ICUs. The proportion of ANZ childhood deaths occurring in ICU was 12%, increasing by 43% over the study period. Unadjusted (0.1% per year, 95% CI 0.096-0.104; p < 0.001) and risk-adjusted (0.1%/year, 95% CI 0.07-0.13; p < 0.001) ICU mortality rates fell. Across all admission sources and diagnostic groups, mortality declined except following pre-ICU cardiopulmonary arrest where increased mortality was observed. Half of the deaths followed withdrawal of life-sustaining therapy (51%), remaining constant throughout the study. Deaths despite maximal resuscitation declined (0.92%/year, 95% CI 0.89-0.95%; p < 0.001) and brain death diagnoses increased (0.72%/year, 95% CI 0.69-0.75%; p = 0.001). CONCLUSIONS: Unadjusted and risk-adjusted mortality for children admitted to ANZ ICUs is declining. Half of pediatric ICU deaths follow withdrawal of life-sustaining therapy. Epidemiology and mode of pediatric ICU death are changing. Further investigation at an international level will inform benchmarking, resource allocation and training requirements for pediatric critical care.