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.

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.

Sub-Clinical Effects of Outdoor Smoke in Affected Communities.

Many Australians are intermittently exposed to landscape fire smoke from wildfires or planned (prescribed) burns. This study aimed to investigate effects of outdoor smoke from planned burns, wildfires and a coal mine fire by assessing biomarkers of inflammation in an exposed and predominantly older population. Participants were recruited from three communities in south-eastern Australia. Concentrations of fine particulate matter (PM2.5) were continuously measured within these communities, with participants performing a range of health measures during and without a smoke event. Changes in biomarkers were examined in response to PM2.5 concentrations from outdoor smoke. Increased levels of FeNO (fractional exhaled nitric oxide) (ß = 0.500 [95%CI 0.192 to 0.808] p < 0.001) at a 4 h lag were associated with a 10 µg/m3 increase in PM2.5 levels from outdoor smoke, with effects also shown for wildfire smoke at 4, 12, 24 and 48-h lag periods and coal mine fire smoke at a 4 h lag. Total white cell (ß = -0.088 [-0.171 to -0.006] p = 0.036) and neutrophil counts (ß = -0.077 [-0.144 to -0.010] p = 0.024) declined in response to a 10 µg/m3 increase in PM2.5. However, exposure to outdoor smoke resulting from wildfires, planned burns and a coal mine fire was not found to affect other blood biomarkers.

Reduction of in-hospital cardiac arrest rates in intensive care-equipped New South Wales hospitals in association with implementation of Between the Flags rapid response system.

BACKGROUND: The NSW Clinical Excellence commission introduced the 'Between the Flags' programme, in response to the death of a young patient, as a system-wide approach for early detection and management of the deteriorating patient in all NSW hospitals. The impact of BTF implementation on the 35 larger hospitals with intensive care units (ICU) has not been reported previously. AIM: To assess the impact of 'Between the Flags' (BTF), a two-tier rapid response system across 35 hospitals with an ICU in NSW, on the incidence of in-hospital cardiac arrests and the incidence and outcome of patients admitted to an ICU following cardiac arrest and rapid response team activation. METHODS: This is a prospective observational study of the BTF registry (August 2010 to June 2016) and the Australian and New Zealand Intensive Care Society Adult Patient Database (January 2008 to December 2016) in 35 New South Wales public hospitals with an ICU. The primary outcome studied was the proportion of in-hospital cardiac arrests. Secondary outcomes included changes in the severity of illness and outcomes of cardiac arrest admissions to the ICU and changes in the volume of rapid response calls. RESULTS: The cardiac arrest rate per 1000 hospital admissions declined from 0.91 in the implementation period to 0.70. Propensity score analysis showed significant declines in ICU and hospital mortality and length of stay for cardiac arrest patients admitted to the ICU (all P < 0.001). CONCLUSIONS: The BTF programme was associated with a significant reduction in cardiac arrests in hospitals and ICU admissions secondary to cardiac arrests in 35 NSW hospitals with an ICU.

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.

The association of coal mine fire smoke with hospital emergency presentations and admissions: Time series analysis of Hazelwood Health Study.

OBJECTIVES: We aimed to examine the change in rates of hospital emergency presentations or hospital admissions during the coal mine fire, and their associations with the coal mine fire-related fine particles (PM2.5). METHODS: Daily data on hospital emergency presentations and admissions were collected from the Department of Health and Human Services for the period January 01, 2009 to June 30, 2015, at Statistical Area Level 2 (SA2). The coal mine fire-related PM2.5 concentrations were modelled by the Chemical Transport Model coupled with the Cubic Conformal Atmospheric Model. A generalised additive mixed model was used to estimate the change in rates of hospital emergency presentations and hospital admissions during the coal mine fire period, and to examine their associations with PM2.5 concentrations for smoke impacted areas, after controlling for potential confounders. RESULTS: Compared with non-fire periods, we found increased risks of all-causes, respiratory diseases, and asthma related emergency presentations and hospital admissions as well as chronic obstructive pulmonary disease (COPD) related emergency presentations during the fire period. Associations between daily concentrations of coal mine fire-related PM2.5 and emergency presentations for all-causes and respiratory diseases, including COPD and asthma, appeared after two days' exposure. Associations with hospital admissions for cerebrovascular and respiratory diseases appeared on the same day of exposure. CONCLUSIONS: Coal mine fire smoke created a substantial health burden. People with respiratory diseases should receive targeted messages, follow self-management plans and take preventive medication during future coal mine fires.

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.

The current temperature: A survey of post-resuscitation care across Australian and New Zealand intensive care units.

AIM: Targeted temperature management (TTM) in post-resuscitation care has changed dramatically over the last two decades. However, uptake across Australian and New Zealand (NZ) intensive care units (ICUs) is unclear. We aimed to describe post-resuscitation care in our region, with a focus on TTM, and to gain insights into clinician's opinions about the level of evidence supporting TTM. METHODS: In December 2017, we sent an online survey to 163 ICU medical directors in Australia (n â€‹= â€‹141) and NZ (n â€‹= â€‹22). RESULTS: Sixty-one ICU medical directors responded (50 from Australia and 11 from NZ). Two respondents were excluded from analysis as their Private ICUs did not admit post-arrest patients. The majority of remaining respondents stated their ICU followed a post-resuscitation care clinical guideline (n â€‹= â€‹41/59, 70%). TTM was used in 57 (of 59, 97%) ICUs, of these only 64% had a specific TTM clinical guideline/policy and there was variation in the types of patients treated, temperatures targeted (range â€‹= â€‹33-37.5 â€‹°C), methods for cooling and duration of cooling (range â€‹= â€‹12-72 â€‹h). The majority of respondents stated that their ICU (n â€‹= â€‹45/57, 88%) changed TTM practice following the TTM trial: with 28% targeting temperatures >36 â€‹°C, and 23 (of 46, 50%) respondents expressed concerns with current level of evidence for TTM. Only 38% of post-resuscitation guidelines included prognostication procedures, few ICUs reported the use of electrophysiological tests. CONCLUSIONS: In Australian and New Zealand ICUs there is widespread variation in post-resuscitation care, including TTM practice and prognostication. There also seems to be concerns with current TTM evidence and recommendations.

RACHS - ANZ : A Modified Risk Adjustment in Congenital Heart Surgery Model for Outcome Surveillance in Australia and New Zealand.

Background Outcomes for pediatric cardiac surgery are commonly reported from international databases compiled from voluntary data submissions. Surgical outcomes for all children in a country or region are less commonly reported. We aimed to describe the bi-national population-based outcome for children undergoing cardiac surgery in Australia and New Zealand and determine whether the Risk Adjustment for Congenital Heart Surgery ( RACHS ) classification could be used to create a model that accurately predicts in-hospital mortality in this population. Methods and Results The study was conducted in all children's hospitals performing cardiac surgery in Australia and New Zealand between January 2007 and December 2015. The performance of the original RACHS -1 model was assessed and compared with an alternative RACHS - ANZ (Australia and New Zealand) model, developed balancing discrimination with parsimonious variable selection. A total of 14 324 hospital admissions were analyzed. The overall hospital mortality was 2.3%, ranging from 0.5% for RACHS category 1 procedures, to 17.0% for RACHS category 5 or 6 procedures. The original RACHS -1 model was poorly calibrated with death overpredicted (1161 deaths predicted, 289 deaths observed). The RACHS - ANZ model had better performance in this population with excellent discrimination (Az- ROC of 0.830) and acceptable Hosmer and Lemeshow goodness-of-fit ( P=0.216). Conclusions The original RACHS -1 model overpredicts mortality in children undergoing heart surgery in the current era. The RACHS - ANZ model requires only 3 risk variables in addition to the RACHS procedure category, can be applied to a wider range of patients than RACHS -1, and is suitable to use to monitor regional pediatric cardiac surgery outcomes.

Defining benefit threshold for extracorporeal membrane oxygenation in children with sepsis-a binational multicenter cohort study.

BACKGROUND: The surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock. METHODS: Retrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO. RESULTS: Five thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864-0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89-2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39-0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10-0.98, p = 0.046) as significant predictors of survival for those treated with VA-ECMO. CONCLUSIONS: This binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.

Temporal Trends in Emergency Medical Services and General Practitioner Use for Acute Stroke After Australian Public Education Campaigns.

Background and Purpose- The Australian Stroke Foundation ran annual paid advertising between 2004 and 2014, using the FAST (Face, Arm, Speech, Time) campaign from 2006 and adding the message to call emergency medical services in 2007. In this study, we examined temporal trends in emergency medical services use and referrals from general practitioners in the Australian state of Victoria to evaluate the impact of these campaigns. Methods- Using data from 33 public emergency departments, contributing to the Victorian Emergency Minimum Dataset, we examined trends in emergency department presentations for 118 000 adults with an emergency diagnosis of stroke or transient ischemic attack between 2003 and 2015. Annual trends were examined using logistic regression using a precampaign period (January 2003 to August 2004) as reference and adjusting for demographic variables. Results- Compared with the precampaign period, significant increases in emergency medical services use were seen annually between 2008 and 2015 (all P<0.001, eg, 2015; adjusted odds ratio, 1.16; 95% CI, 1.10-1.23). In contrast, a decrease was seen in patients presenting via general practitioners across all campaign years (all P<0.001, eg, 2015; adjusted odds ratio, 0.48; 95% CI, 0.44-0.53). Conclusions- Since the Stroke Foundation campaigns began, a greater proportion of stroke and transient ischemic attack patients are presenting to hospital by emergency medical services and appear to be bypassing their general practitioners.

Identifying barriers to the provision of bystander cardiopulmonary resuscitation (CPR) in high-risk regions: A qualitative review of emergency calls.

INTRODUCTION: Understanding regional variation in bystander cardiopulmonary resuscitation (CPR) is important to improving out-of-hospital cardiac arrest (OHCA) survival. In this study we aimed to identify barriers to providing bystander CPR in regions with low rates of bystander CPR and where OHCA was recognised in the emergency call. METHODS: We retrospectively reviewed emergency calls for adults in regions of low bystander CPR in the Australian state of Victoria. Included calls were those where OHCA was identified during the call but no bystander CPR was given. A thematic content analysis was independently conducted by two investigators. RESULTS: Saturation of themes was reached after listening to 139 calls. Calls progressed to the point of compression instructions before EMS arrival in only 26 (18.7%) of cases. Three types of barriers were identified: procedural barriers (time lost due to language barriers and communication issues; telephone problems), CPR knowledge (skill deficits; perceived benefit) and personal factors (physical frailty or disability; patient position; emotional factors). CONCLUSION: A range of factors are associated with barriers to delivering bystander CPR even in the presence of dispatcher instructions - some of which are modifiable. To overcome these barriers in high-risk regions, targeted public education needs to provide information about what occurs in an emergency call, how to recognise an OHCA and to improve CPR knowledge and skills.

Prognostic accuracy of age-adapted SOFA, SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit.

PURPOSE: The Sepsis-3 consensus task force defined sepsis as life-threatening organ dysfunction caused by dysregulated host response to infection. However, the clinical criteria for this definition were neither designed for nor validated in children. We validated the performance of SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores as predictors of outcome in children. METHODS: We performed a multicentre binational cohort study of patients < 18 years admitted with infection to ICUs in Australia and New Zealand. The primary outcome was ICU mortality. SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores were compared using crude and adjusted area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: Of 2594 paediatric ICU admissions due to infection, 151 (5.8%) children died, and 949/2594 (36.6%) patients died or experienced an ICU length of stay ≥ 3 days. A ≥ 2-point increase in the individual score was associated with a crude mortality increase from 3.1 to 6.8% for SIRS, from 1.9 to 7.6% for age-adapted SOFA, from 1.7 to 7.3% for PELOD-2, and from 3.9 to 8.1% for qSOFA (p < 0.001). The discrimination of outcomes was significantly higher for SOFA (adjusted AUROC 0.829; 0.791-0.868) and PELOD-2 (0.816; 0.777-0.854) than for qSOFA (0.739; 0.695-0.784) and SIRS (0.710; 0.664-0.756). CONCLUSIONS: SIRS criteria lack specificity to identify children with infection at substantially higher risk of mortality. We demonstrate that adapting Sepsis-3 to age-specific criteria performs better than Sepsis-2-based criteria. Our findings support the translation of Sepsis-3 into paediatric-specific sepsis definitions and highlight the importance of robust paediatric organ dysfunction characterization.

Predicting outcomes in traumatic out-of-hospital cardiac arrest: the relevance of Utstein factors.

BACKGROUND: Given low survival rates in cases of traumatic out-of-hospital cardiac arrest (OHCA), there is a need to identify factors associated with outcomes. We aimed to investigate Utstein factors associated with achieving return of spontaneous circulation (ROSC) and survival to hospital in traumatic OHCA. METHODS: The Victorian Ambulance Cardiac Arrest Registry (VACAR) was used to identify cases of traumatic OHCA that received attempted resuscitation and occurred between July 2008 and June 2014. We excluded cases aged <16 years or with a mechanism of hanging or drowning. RESULTS: Of the 660 traumatic OHCA patients who received attempted resuscitation, ROSC was achieved in 159 patients (24%) and 95 patients (14%) survived to hospital (ROSC on hospital handover). Factors that were positively associated with achieving ROSC in multivariable logistic regression models were age ≥65 years (adjusted OR (AOR)=1.56, 95% CI: 1.01 to 2.43) and arresting rhythm (shockable (AOR=3.65, 95% CI: 1.64 to 8.11) and pulseless electrical activity (AOR=2.15, 95% CI: 1.36 to 3.39) relative to asystole). Similarly, factors positively associated with survival to hospital were arresting rhythm (shockable (AOR=3.92, 95% CI: 1.64 to 9.41) relative to asystole), and the mechanism of injury (falls (AOR=2.16, 95% CI: 1.03 to 4.54) relative to motor vehicle collisions), while trauma type (penetrating (AOR=0.27, 95% CI: 0.08 to 0.91) relative to blunt trauma) and event region (rural (AOR=0.39, 95% CI: 0.19 to 0.80) relative to urban) were negatively associated with survival to hospital. CONCLUSIONS: Few patient and arrest characteristics were associated with outcomes in traumatic OHCA. These findings suggest there is a need to incorporate additional information into cardiac arrest registries to assist prognostication and the development of novel interventions in these trauma patients.

Coagulation monitoring correlation with heparin dose in pediatric extracorporeal life support.

OBJECTIVES: Extracorporeal Life Support (ECLS) risks thrombotic and hemorrhagic complications. Optimal anti-coagulation monitoring is controversial. We compared coagulation tests evaluating the heparin effect in pediatric ECLS. METHODS: A retrospective study of children (<18yrs) undergoing ECLS over 12 months in a tertiary pediatric intensive care unit (PICU). Variables included anti-Factor Xa activity (anti-Xa), activated partial thromboplastin time (aPTT), activated clotting time (ACT) and thromboelastogram (TEG®6s) parameters: ratio and delta reaction (R) times (the ratio and difference, respectively, between R times in kaolin assays with and without heparinase). Test results were correlated with unfractionated heparin infusion rate (IU/kg/hr) at the time of sampling. Mean test results of each ECLS run were evaluated according to the presence/absence of complications. RESULTS: Thirty-two ECLS runs (31 patients) generated 695 data-points for correlation. PICU mortality was 22% and the thrombotic complication rate was 66%. The proportion of variation in coagulation test results explained by heparin dose was 13.3% for anti-Xa, 11.9% for ratio R time, and 9.9% for delta R time, compared with <1% for ACT and aPTT. Incorporating individual variation, age and antithrombin activity in a model with heparin dose explained less than 50% of the variation in test results. Correlation varied according to age, day of ECLS run and between individuals, with parallel dose-response lines noted between patients. Significantly lower mean anti-Xa was observed in PICU non-survivors and runs with thrombosis. CONCLUSION: Lower anti-Xa was observed in ECLS runs with complications. Although absolute results from anti-Xa and TEG6®s showed the best correlation with heparin dose, a large proportion of variation in results was unexplained by heparin, while dose response was similar between individuals. Population pharmacokinetic/pharmacodynamic modelling is required, as well as prospective trials to delineate the superior means of adjusting heparin therapy to prevent adverse clinical outcomes.

Burden of disease and change in practice in critically ill infants with bronchiolitis.

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs).We assessed changes in admission rate, respiratory support, and outcomes of infants <24 months with bronchiolitis admitted to ICU between 2002 and 2014 in Australia and New Zealand.During the study period, bronchiolitis was responsible for 9628 (27.6%) of 34 829 non-elective ICU admissions. The estimated population-based ICU admission rate due to bronchiolitis increased by 11.76 per 100 000 each year (95% CI 8.11-15.41). The proportion of bronchiolitis patients requiring intubation decreased from 36.8% in 2002, to 10.8% in 2014 (adjusted OR 0.35, 95% CI 0.27-0.46), whilst a dramatic increase in high-flow nasal cannula therapy use to 72.6% was observed (p<0.001). We observed considerable variability in practice between units, with six-fold differences in risk-adjusted intubation rates that were not explained by ICU type, size, or major patient factors. Annual direct hospitalisation costs due to severe bronchiolitis increased to over USD30 million in 2014.We observed an increasing healthcare burden due to severe bronchiolitis, with a major change in practice in the management from invasive to non-invasive support that suggests thresholds to admittance of bronchiolitis patients to ICU have changed. Future studies should assess strategies for management of bronchiolitis outside ICUs.