Sepsis epidemiology in Australian and New Zealand children (SENTINEL): protocol for a multicountry prospective observational study.

INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes. METHODS AND ANALYSIS: This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures. ETHICS AND DISSEMINATION: Ethics approval was received from the Royal Children's Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000920897; Pre-results.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults.

Importance: In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. Objective: To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). Design, Setting, and Participants: This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. Exposure: The primary exposure was time to CRRT initiation from intensive care unit admission. Main Outcomes and measures: The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Results: Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). Conclusions and Relevance: In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

A Clinical Score for Quantifying Edema in Mechanically Ventilated Children With Congenital Heart Disease in Intensive Care.

Standardized clinical measurements of edema do not exist. OBJECTIVES: To describe a 19-point clinical edema score (CES), investigate its interobserver agreement, and compare changes between such CES and body weight. DESIGN SETTING AND PARTICIPANTS: Prospective observational study in a tertiary PICU of mechanically ventilated children with congenital heart disease. MAIN OUTCOMES AND MEASURES: Differences in the median CES between observer groups. RESULTS: We studied 61 children, with a median age of 8.0 days (interquartile range, 1.0-14.0 d). A total of 539 CES were performed by three observer groups (medical 1 [reference], medical 2, and bedside nurse) at 0, 24, and 48 hours from enrollment. Overall, there was close agreement between observer groups in mean, median, and upper quartile of CES scores, with least agreement observed in the lower quartile of scores. Across all quartiles of CES, after adjusting for baseline weight, cardiac surgical risk, duration of cardiopulmonary bypass, or peritoneal dialysis during the study, observer groups returned similar mean scores (medical 2: 25th centile +0.1 [95% CI, -0.2 to 0.5], median +0.6 [95% CI, -0.4 to 1.5], 75th centile +0.1 [95% CI, -1.1 to 1.4] and nurse: 25th centile +0.5 [95% CI, 0.0-0.9], median +0.7 [95% CI, 0.0-1.5], 75th centile -0.2 [95% CI, -1.3 to 1.0]) Within a multivariable mixed-effects linear regression model, including adjustment for baseline CES, each 1 point increase in CES was associated with a 12.1 grams (95% CI, 3.2-21 grams) increase in body weight. CONCLUSIONS AND RELEVANCE: In mechanically ventilated children with congenital heart disease, three groups of observers tended to agree when assessing overall edema using an ordinal clinical score assessed in six body regions, with agreement least at low edema scores. An increase in CES was associated with an increase in body weight, suggesting some validity for quantifying edema. Further exploration of the CES as a rapid clinical tool is indicated.

Adaptive Clinical Trials in Pediatric Critical Care: A Systematic Review.

OBJECTIVES: This systematic review investigates the use of adaptive designs in randomized controlled trials (RCTs) in pediatric critical care. DATA SOURCES: PICU RCTs, published between 1986 and 2020, stored in the www.PICUtrials.net database and MEDLINE, EMBASE, CENTRAL, and LILACS databases were searched (March 9, 2022) to identify RCTs published in 2021. PICU RCTs using adaptive designs were identified through an automated full-text screening algorithm. STUDY SELECTION: All RCTs involving children (< 18 yr old) cared for in a PICU were included. There were no restrictions to disease cohort, intervention, or outcome. Interim monitoring by a Data and Safety Monitoring Board that was not prespecified to change the trial design or implementation of the study was not considered adaptive. DATA EXTRACTION: We extracted the type of adaptive design, the justification for the design, and the stopping rule used. Characteristics of the trial were also extracted, and the results summarized through narrative synthesis. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. DATA SYNTHESIS: Sixteen of 528 PICU RCTs (3%) used adaptive designs with two types of adaptations used; group sequential design and sample size reestimation. Of the 11 trials that used a group sequential adaptive design, seven stopped early due to futility and one stopped early due to efficacy. Of the seven trials that performed a sample size reestimation, the estimated sample size decreased in three trials and increased in one trial. CONCLUSIONS: Little evidence of the use of adaptive designs was found, with only 3% of PICU RCTs incorporating an adaptive design and only two types of adaptations used. Identifying the barriers to adoption of more complex adaptive trial designs is needed.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a statistical analysis plan for a randomised controlled trial.

The placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.

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

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

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

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

Characteristics, management and changing incidence of children with empyema in a paediatric intensive care unit.

AIM: Paediatric intensive care unit (PICU) admissions for empyema increased following the 13-valent pneumococcal conjugate vaccine (PCV13). We describe the clinical characteristics, management and outcomes for children with empyema and compare incidence before and after PCV13. METHODS: Retrospective study of patients <18 years admitted to The Royal Children's Hospital Melbourne PICU with empyema between January 2016 and July 2019. We investigated the incidence of empyema during two time periods: 2007-2010 (pre-PCV13) and 2016-2019 (post-PCV13). RESULTS: Seventy-one children (1.9% of all PICU admissions) were admitted to PICU with empyema between 2016 and 2019. Sixty-one (86%) had unilateral disease, 11 (16%) presented with shock and 44 (62%) were ventilated. Streptococcus pneumoniae and group A Streptococcus were the most commonly identified pathogens. Forty-five (63%) were managed with video-assisted thoracoscopic surgery (VATS). There was a 31% reduction in empyema hospitalisations as a proportion of all hospitalisations (IRR 0.69, 95% CI 0.59-0.8), but a 2.8-fold increase in empyema PICU admissions as a proportion of all PICU admissions (95% CI 2.2-3.5, P < 0.001). For the PICU cohort, this was accompanied by reduction in PIM2 probability of death (median 1% vs. 1.9%, P = 0.02) and duration of intubation (median 69 h vs. 126.5 h, P = 0.045). CONCLUSIONS: In children with empyema in PICU 62% required ventilation, 16% had features of shock and 63% received VATS. Empyema admissions, as a proportion of all PICU admissions, increased in the era post-PCV13 compared to pre-PCV13 despite no increase in illness severity at admission.

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

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

Characteristics and Physiologic Changes After 4% Albumin Fluid Boluses in a PICU.

OBJECTIVES: To describe the characteristics, hemodynamic, and physiologic changes after 4% albumin fluid boluses in critically ill children. DESIGN: Retrospective observational study. SETTING: Single-center PICU. PATIENTS: Children in a cardiac and general PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between January 2017 and May 2019, there were 1,003 fluid boluses of 4% albumin during 420 of 5,731 admissions (7.8%), most commonly in children with congenital/acquired heart disease (71.2%) and sepsis (7.9%). The median fluid bolus dose was 10 mL/kg (interquartile range, 5.8-14.6 mL/kg), and its duration 30 minutes (interquartile range, 14.0-40.0 min; n = 223). After the fluid bolus, a significant change in mean arterial pressure (2.3 mm Hg [5.1%], 2.7 mm Hg [5.8%], 2.9 mm Hg [6.1%], and 3.8 mm Hg [8.0%] at 1, 2, 3, and 4 hr, respectively [p ≤ 0.001]) only occurred in children less than or equal to 12 months old. A mean arterial pressure response, defined by an increase greater than or equal to 10% from baseline, occurred in 290 of 887 patients (33%) with maximal response at 1 hour. Hypotension at baseline predicted the magnitude of mean arterial pressure increase at 60 (coefficient 24.3 [95% CI, 0.79-7.87]; p = 0.04) and 120 minutes (coefficient 26.1 [95% CI, 2.75-48.2]; p = 0.02). There were no biochemical or hematocrit changes within 4 hours of the fluid bolus. Urine output for the entire cohort was 2 mL/kg/hr at baseline and did not change with the fluid bolus. CONCLUSIONS: Fluid boluses of 4% albumin were common and predominantly in children with cardiac disease and sepsis with a median dose of 10 mL/kg given over half an hour. Such treatment was associated with significant hemodynamic changes only in children less than 12 months old, and we failed to identify an association with urine output.

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

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

PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial.

BACKGROUND/AIMS: Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock. METHODS: The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under "exception from informed consent" in the USA or "deferred consent" in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed. DISCUSSION: PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings. TRIAL REGISTRATION: PRoMPT BOLUS was first registered at ClinicalTrials.gov ( NCT04102371 ) on September 25, 2019. Enrollment started on August 25, 2020.

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.

Characteristics and outcomes of children receiving intensive care therapy within 12 hours following a medical emergency team event.

Objectives: To describe characteristics and outcomes of children requiring intensive care therapy (ICT) within 12 hours following a medical emergency team (MET) event. Design: Retrospective cohort study. Setting: Quaternary paediatric hospital. Patients: Children experiencing a MET event. Measurements and main results: Between July 2017 and March 2019, 890 MET events occurred in 566 patients over 631 admissions. Admission to intensive care followed 183/890 (21%) MET events. 76/183 (42%) patients required ICT, defined as positive pressure ventilation or vasoactive support in intensive care, within 12 hours. Older children had a lower risk of requiring ICT than infants aged < 1 year (age 1-5 years [risk difference, -6.4%; 95% CI, -11% to -1.6%; P = 0.01] v age > 5 years [risk difference, -8.0%; 95% CI, -12% to -3.8%; P < 0.001]), while experiencing a critical event increased this risk (risk difference, 16%; 95% CI, 3.3-29%; P = 0.01). The duration of respiratory support and intensive care length of stay was approximately double in patients requiring ICT (ratio of geometric means, 2.0 [95% CI, 1.4-3.0] v 2.1 [95% CI, 1.5-2.8]; P < 0.001) and the intensive care mortality increased (risk difference, 9.6%; 95% CI, 2.4-17%; P = 0.01). Heart rate, oxygen saturation and respiratory rate were the most commonly measured vital signs in the 6 hours before the MET event. Conclusions: Approximately one-fifth of MET events resulted in intensive care admission and nearly half of these required ICT within 12 hours. This group had greater duration of respiratory support, intensive care and hospital length of stay, and higher mortality. Age < 1 year and a critical event increased the risk of ICT.

Interhospital transport of children with bronchiolitis by a statewide emergency transport service.

Objective: To investigate the rate of interhospital emergency transport for bronchiolitis and intensive care admission following the introduction of high flow nasal cannula and standardised paediatric observation and response charts. Design: Retrospective cohort study. Setting: A statewide paediatric intensive care transport service and its two referral paediatric intensive care units (PICUs) in Victoria, Australia. Participants: Children less than 2 years old emergently transported with bronchiolitis during two time periods: 2008-2012 and 2015-2019. Main outcome measures: Incidence rates of bronchiolitis transport episodes, PICU admissions and respiratory support. Results: 802 children with bronchiolitis were transported during the study period, 233 in the first period (2008-2012) and 569 in the second period (2015-2019). The rate of interhospital transport for bronchiolitis increased from 32.9 to 71.8 per 100 000 children aged 0-2 years. The population-adjusted rate of PICU admission increased from 16.2 to 36.6 per 100 000 children aged 0-2 years. Metropolitan hospitals were the predominant referral source and this increased from 60.1% of transports to 78.6% (P < 0.001). In children admitted to a PICU, the administration of high flow nasal cannula during transport increased significantly from 1.7% to 75.9% (P < 0.001) and a concomitant reduction in continuous positive airway pressure and mechanical ventilation occurred (40-12.4% and 27-6.9% respectively; P < 0.001). The proportion of mechanical ventilation as well as PICU and hospital length of stay decreased over time. Conclusions: The population-adjusted rate of interhospital transport and admission to the PICU for bronchiolitis increased over time. This occurred despite a lower rate of non-invasive and invasive mechanical ventilation during transport and in the PICU.

Precision of weight measurement in critically ill infants: a technical report.

Objectives: To investigate the precision of weight measurements in critically ill infants in a paediatric intensive care unit (PICU). Design: Prospective cohort study. Setting: Royal Children's Hospital PICU. Participants: Mechanically ventilated infants admitted to the Royal Children's Hospital PICU between September 2020 and February 2021. Main outcome measures: Mean percentage difference and agreement of consecutive weight measurements. Results: Thirty infants were enrolled, of which 17 were receiving post-surgical care for congenital heart disease and four were receiving extracorporeal membrane oxygenation (ECMO). The median age was 13 days (interquartile range [IQR], 3.1-52.4 days). The mean difference in weight was 1.3% (standard deviation [SD], 1.0%), and the test-retest agreement intraclass correlation was 0.99 (95% CI, 0.99-0.99; P < 0.01). The percentage difference between measurements was ≤ 2.5% in 26/30 (87%) children, and the range was < 0.1% to 3.6%. In 26 children not receiving ECMO, the mean difference in weight was 1.1% (SD, 1.0%). There were no complications. Conclusions: Weighing mechanically ventilated, critically ill infants in intensive care can be performed safely, with a mean difference between consecutive weights of 1.3%, making it a potentially useful additional measure of fluid accumulation.

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

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