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.

Definition, Incidence, and Epidemiology of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: In 2015, the Pediatric Acute Lung Injury Consensus Conference (PALICC) provided the first pediatric-specific definitions for acute respiratory distress syndrome (pediatric acute respiratory distress syndrome [PARDS]). These definitions have since been operationalized in cohort and interventional PARDS studies. As substantial data have accrued since 2015, we have an opportunity to assess the construct validity and utility of the initial PALICC definitions. Therefore, the Second PALICC (PALICC-2) brought together multiple PARDS experts and aimed to identify and summarize relevant evidence related to the definition and epidemiology of PARDS and create modifications to the definition of PARDS. DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies of subjects with PARDS, or at risk for PARDS, excluding studies pertaining primarily to adults except as specified for identifying age-specific cutoffs. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. A total of 97 studies were identified for full-text extraction addressing distinct aspects of the PARDS definition, including age, timing, imaging, oxygenation, modes of respiratory support, and specific coexisting conditions. Data were assessed in a Patient/Intervention/Comparator/Outcome format when possible, and formally summarized for effect size, risk, benefit, feasibility of implementation, and equity. A total of 17 consensus-based definition statements were made that update the definition of PARDS, as well as the related diagnoses of "Possible PARDS" and "At-Risk for PARDS." These statements are presented alongside a summary of the relevant epidemiology. CONCLUSIONS: We present updated, data-informed consensus statements on the definition for PARDS and the related diagnoses of "Possible PARDS" and "At-Risk for PARDS."

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Clinical care of children and adolescents with COVID-19: recommendations from the National COVID-19 Clinical Evidence Taskforce.

INTRODUCTION: The epidemiology and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are different in children and adolescents compared with adults. Although coronavirus disease 2019 (COVID-19) appears to be less common in children, with milder disease overall, severe complications may occur, including paediatric inflammatory multisystem syndrome (PIMS-TS). Recognising the distinct needs of this population, the National COVID-19 Clinical Evidence Taskforce formed a Paediatric and Adolescent Care Panel to provide living guidelines for Australian clinicians to manage children and adolescents with COVID-19 and COVID-19 complications. Living guidelines mean that these evidence-based recommendations are updated in near real time to give reliable, contemporaneous advice to Australian clinicians providing paediatric care. MAIN RECOMMENDATIONS: To date, the Taskforce has made 20 specific recommendations for children and adolescents, including definitions of disease severity, recommendations for therapy, respiratory support, and venous thromboembolism prophylaxis for COVID-19 and for the management of PIMS-TS. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: The Taskforce currently recommends corticosteroids as first line treatment for acute COVID-19 in children and adolescents who require oxygen. Tocilizumab could be considered, and remdesivir should not be administered routinely in this population. Non-invasive ventilation or high flow nasal cannulae should be considered in children and adolescents with hypoxaemia or respiratory distress unresponsive to low flow oxygen if appropriate infection control measures can be used. Children and adolescents with PIMS-TS should be managed by a multidisciplinary team. Intravenous immunoglobulin and corticosteroids, with concomitant aspirin and thromboprophylaxis, should be considered for the treatment of PIMS-TS. The latest updates and full recommendations are available at www.covid19evidence.net.au.

People in intensive care with COVID-19: demographic and clinical features during the first, second, and third pandemic waves in Australia.

OBJECTIVE: To compare the demographic and clinical features, management, and outcomes for patients admitted with COVID-19 to intensive care units (ICUs) during the first, second, and third waves of the pandemic in Australia. DESIGN, SETTING, AND PARTICIPANTS: People aged 16 years or more admitted with polymerase chain reaction-confirmed COVID-19 to the 78 Australian ICUs participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project during the first (27 February - 30 June 2020), second (1 July 2020 - 25 June 2021), and third COVID-19 waves (26 June - 1 November 2021). MAIN OUTCOME MEASURES: Primary outcome: in-hospital mortality. SECONDARY OUTCOMES: ICU mortality; ICU and hospital lengths of stay; supportive and disease-specific therapies. RESULTS: 2493 people (1535 men, 62%) were admitted to 59 ICUs: 214 during the first (9%), 296 during the second (12%), and 1983 during the third wave (80%). The median age was 64 (IQR, 54-72) years during the first wave, 58 (IQR, 49-68) years during the second, and 54 (IQR, 41-65) years during the third. The proportion without co-existing illnesses was largest during the third wave (41%; first wave, 32%; second wave, 29%). The proportion of ICU beds occupied by patients with COVID-19 was 2.8% (95% CI, 2.7-2.9%) during the first, 4.6% (95% CI, 4.3-5.1%) during the second, and 19.1% (95% CI, 17.9-20.2%) during the third wave. Non-invasive (42% v 15%) and prone ventilation strategies (63% v 15%) were used more frequently during the third wave than during the first two waves. Thirty patients (14%) died in hospital during the first wave, 35 (12%) during the second, and 281 (17%) during the third. After adjusting for age, illness severity, and other covariates, the risk of in-hospital mortality was similar for the first and second waves, but 9.60 (95% CI, 3.52-16.7) percentage points higher during the third than the first wave. CONCLUSION: The demographic characteristics of patients in intensive care with COVID-19 and the treatments they received during the third pandemic wave differed from those of the first two waves. Adjusted in-hospital mortality was highest during the third wave.

Outcomes for patients with COVID-19 admitted to Australian intensive care units during the first four months of the pandemic.

OBJECTIVES: To describe the characteristics and outcomes of patients with COVID-19 admitted to intensive care units (ICUs) during the initial months of the pandemic in Australia. DESIGN, SETTING: Prospective, observational cohort study in 77 ICUs across Australia. PARTICIPANTS: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 during 27 February - 30 June 2020. MAIN OUTCOME MEASURES: ICU mortality and resource use (ICU length of stay, peak bed occupancy). RESULTS: The median age of the 204 patients with COVID-19 admitted to intensive care was 63.5 years (IQR, 53-72 years); 140 were men (69%). The most frequent comorbid conditions were obesity (40% of patients), diabetes (28%), hypertension treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (24%), and chronic cardiac disease (20%); 73 patients (36%) reported no comorbidity. The most frequent source of infection was overseas travel (114 patients, 56%). Median peak ICU bed occupancy was 14% (IQR, 9-16%). Invasive ventilation was provided for 119 patients (58%). Median length of ICU stay was greater for invasively ventilated patients than for non-ventilated patients (16 days; IQR, 9-28 days v 3 days; IQR, 2-5 days), as was ICU mortality (26 deaths, 22%; 95% CI, 15-31% v four deaths, 5%; 95% CI, 1-12%). Higher Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores on ICU day 1 (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.09-1.21) and chronic cardiac disease (aHR, 3.38; 95% CI, 1.46-7.83) were each associated with higher ICU mortality. CONCLUSION: Until the end of June 2020, mortality among patients with COVID-19 who required invasive ventilation in Australian ICUs was lower and their ICU stay longer than reported overseas. Our findings highlight the importance of ensuring adequate local ICU capacity, particularly as the pandemic has not yet ended.

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 burden of invasive infections in critically ill Indigenous children in Australia.

OBJECTIVES: To describe the incidence and mortality of invasive infections in Indigenous children admitted to paediatric and general intensive care units (ICUs) in Australia. DESIGN: Retrospective multi-centre cohort study of Australian and New Zealand Paediatric Intensive Care Registry data. PARTICIPANTS: All children under 16 years of age admitted to an ICU in Australia, 1 January 2002 - 31 December 2013. Indigenous children were defined as those identified as Aboriginal and/or Torres Strait Islander in a mandatory admissions dataset. MAIN OUTCOMES: Population-based ICU mortality and admission rates. RESULTS: Invasive infections accounted for 23.0% of non-elective ICU admissions of Indigenous children (726 of 3150), resulting in an admission rate of 47.6 per 100 000 children per year. Staphylococcus aureus was the leading pathogen identified in children with sepsis/septic shock (incidence, 4.42 per 100 000 Indigenous children per year; 0.57 per 100 000 non-Indigenous children per year; incidence rate ratio 7.7; 95% CI, 5.8-10.1; P < 0.001). While crude and risk-adjusted ICU mortality related to invasive infections was not significantly different for Indigenous and non-Indigenous children (odds ratio, 0.75; 95% CI, 0.53-1.07; P = 0.12), the estimated population-based age-standardised mortality rate for invasive infections was significantly higher for Indigenous children (2.67 per 100 000 per year v 1.04 per 100 000 per year; crude incidence rate ratio, 2.65; 95% CI, 1.88-3.64; P < 0.001). CONCLUSIONS: The ICU admission rate for severe infections was several times higher for Indigenous than for non-Indigenous children, particularly for S. aureus infections. While ICU case fatality rates were similar, the population-based mortality was more than twice as high for Indigenous children. Our study highlights an important area of inequality in health care for Indigenous children in a high income country that needs urgent attention.

Comparison of baseline characteristics, treatment and celinical outcomes of critically ill COVID-19 patients admitted in the first and second waves in Australia.

Objective: To report longitudinal differences in baseline characteristics, treatment, and outcomes in patients with coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) between the first and second waves of COVID-19 in Australia. Design, setting and participants: SPRINT-SARI Australia is a multicentre, inception cohort study enrolling adult patients with COVID-19 admitted to participating ICUs. The first wave of COVID-19 was from 27 February to 30 June 2020, and the second wave was from 1 July to 22 October 2020. Results: A total of 461 patients were recruited in 53 ICUs across Australia; a higher number were admitted to the ICU during the second wave compared with the first: 255 (55.3%) versus 206 (44.7%). Patients admitted to the ICU in the second wave were younger (58.0 v 64.0 years; P = 0.001) and less commonly male (68.9% v 60.0%; P = 0.045), although Acute Physiology and Chronic Health Evaluation (APACHE) II scores were similar (14 v 14; P = 0.998). High flow oxygen use (75.2% v 43.4%; P < 0.001) and non-invasive ventilation (16.5% v 7.1%; P = 0.002) were more common in the second wave, as was steroid use (95.0% v 30.3%; P < 0.001). ICU length of stay was shorter (6.0 v 8.4 days; P = 0.003). In-hospital mortality was similar (12.2% v 14.6%; P = 0.452), but observed mortality decreased over time and patients were more likely to be discharged alive earlier in their ICU admission (hazard ratio, 1.43; 95% CI, 1.13-1.79; P = 0.002). Conclusion: During the second wave of COVID-19 in Australia, ICU length of stay and observed mortality decreased over time. Multiple factors were associated with this, including changes in clinical management, the adoption of new evidence-based treatments, and changes in patient demographic characteristics but not illness severity.

A case series of critically ill patients with anti- N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis causes autonomic disturbances, behavioural changes and abnormal movements. It is often a paraneoplastic phenomenon that occurs in association with ovarian teratomas and is the most common paraneoplastic encephalitis. We report nine cases of critically ill patients with anti- NMDA receptor encephalitis from Australia and New Zealand. One patient died and one had a poor neurological recovery. The remaining patients made substantial or complete neurological recoveries. This case series highlights that patients with anti-NMDA receptor encephalitis: • often require long periods of support in an intensive care unit; • may develop tracheostomy complications related to hypersalivation; • may develop life-threatening hyperthermia; • can have ovarian teratomas despite normal investigations; and • often have very abnormal movements that are difficult to control and make ongoing care difficult.