Paediatrics (RCH) - Research Publications
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ItemPrevalence and predictors of poor outcome in children with febrile neutropaenia presenting to the emergency department(WILEY, 2022-10)OBJECTIVE: Children with acquired neutropaenia due to cancer chemotherapy are at high risk of severe infection. The present study aims to describe the prevalence and predictors of poor outcomes in children with febrile neutropaenia (FN). METHODS: This is a multicentre, prospective observational study in tertiary Australian EDs. Cancer patients with FN were included. Fever was defined as a single temperature ≥38°C, and neutropaenia was defined as an absolute neutrophil count <1000/mm3 . The primary outcome was the ICU admission for organ support therapy (inotropic support, mechanical ventilation, renal replacement therapy, extracorporeal life support). Secondary outcomes were: ICU admission, ICU length of stay (LOS) ≥3 days, proven or probable bacterial infection, hospital LOS ≥7 days and 28-day mortality. Initial vital signs, biomarkers (including lactate) and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction-2 were evaluated as predictors of poor outcomes. RESULTS: Between December 2016 and January 2018, 2124 episodes of fever in children with cancer were screened, 547 episodes in 334 children met inclusion criteria. Four episodes resulted in ICU admission for organ support therapy, nine episodes required ICU admission, ICU LOS was ≥3 days in four, hospital LOS was ≥7 days in 153 and two patients died within 28 days. Vital signs, blood tests and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction-2, performed poorly as predictors of these outcomes (area under the receiver operating characteristic curve <0.6). CONCLUSIONS: Very few patients with FN required ICU-level care. Vital signs, biomarkers and clinical sepsis scores for the prediction of poor outcomes are of limited utility in children with FN.
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ItemPRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial(BMC, 2021-11-06)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.
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ItemEpidemiology and effects of fluid bolus administration in the paediatric emergency department(WILEY, 2020-06)OBJECTIVE: Fluid bolus therapy (FBT) is recommended as the initial form of acute circulatory support for many disease processes. The epidemiology of its use in the ED is unknown. The aim of this study was to assess indications, use patterns and short-term effects of FBT in a paediatric ED. METHODS: Retrospective observational study in the ED of the Royal Children's Hospital, Melbourne, Australia (annual census >90 000) using hospital electronic medical record data for all patients who received an i.v. fluid bolus in the ED over the calendar year 2018 were included in the study. We extracted demographics, indications, volume, content of FBT as well as subsequent vital sign and biochemical changes. RESULTS: One thousand five hundred and thirty-nine fluid boluses were administered to 1343/90 000 children (1.5%), 1185 received 1, 123 received 2, 32 received 3, and 3 received 4 boluses. Fluid bolus volume of 10 mL/kg was used in 45.3%, 20 mL/kg in 35.7%, 500 mL in 6.4% and 1000 mL in 7.1%. The fluid content was 0.9% saline in 99.9% of cases. The most common indications for FBT were: vomiting/diarrhoea (23%), acute febrile illness (11%) and pneumonia or sepsis (10% each). FBT was associated with a reduction in median heart rate by 6 beats per minute (P < 0.01), reduction in mean blood pressure by 3 mmHg (P < 0.01), and reduction in venous lactate by 0.2 mmol/L (P < 0.01). CONCLUSIONS: Fluid bolus therapy is a commonly used intervention in the paediatric ED, most often for dehydration. Variability in indications, dose and effects of FBT warrant further exploration.
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ItemDoes fluid bolus therapy increase blood pressure in children with sepsis?(WILEY, 2020-02)OBJECTIVE: To describe the effect of fluid bolus therapy (FBT) on blood pressure in children with sepsis. Secondary outcomes included the effect of FBT on systemic vascular resistance, shock index and shock phenotype (warm or cold). METHODS: This was a prospective observational study in the ED of The Royal Children's Hospital, Melbourne, Australia. Participants were children meeting international consensus criteria for sepsis who received FBT for tachycardia or hypotension. FBT was defined as 10-20 mL/kg of 0.9% saline. Mean blood pressure (MBP) was recorded at baseline, 5 and 60 min after FBT. Total systemic vascular resistance index (TSVRi), shock index, and shock phenotype were derived for each time point. Hypotension was defined as MBP <55 + 1.5 × age (years). Warm shock was defined as TSVRi <800 dyne s/cm5 /m2 . RESULTS: Fifty fluid boluses were recorded in 41 children. Median MBP was 78 mmHg (interquartile range [IQR] 63-86) at baseline, 72 mmHg (IQR 60-82) at 5 min, and 75 mmHg (IQR 66-84) at 60 min. Hypotension was observed in 16% at baseline, 26% at 5 min and 17% at 60 min. Median TSVRi was 1580 dyne s/cm5 /m2 (IQR 1242-2206) at baseline, 1254 dyne s/cm5 /m2 (IQR 1027-1787) at 5 min, and 1850 dyne s/cm5 /m2 (IQR 1265-2140) at 60 min. Median shock index was 1.60 (IQR 1.34-1.90) at baseline, 1.49 (IQR 1.25-1.76) at 5 min and 1.37 (IQR 1.22-1.61) at 60 min. Two percent of cases had warm shock at baseline, 12% at 5 min and 2% at 60 min. CONCLUSIONS: MBP initially decreased following FBT for paediatric sepsis, returning towards baseline over the subsequent 60 min. The utility of FBT for increasing MBP and its effect on patient-centred outcomes in children with sepsis warrants further exploration.
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ItemReview article: A primer for clinical researchers in the emergency department: Part IX. How to conduct a systematic review in the field of emergency medicine(WILEY, 2019-08)In this series we address important topics for emergency clinicians who either participate in research as part of their work, or use the knowledge generated by research studies. Emergency clinicians are routinely in the position of applying new evidence in clinical practice. With an ever-increasing volume of evidence generated, this can be problematic when studies are conducted in different settings, and include different patient groups, different interventions and different outcomes. This is made even more difficult when the results of primary research studies do not agree. Systematic reviews are becoming increasingly valuable as they appraise and synthesise research findings using a clear methodology, and summarise the results of primary studies. As such, systematic reviews help translate research findings into clinical practice. This paper provides a practical starting point for understanding the steps involved in conducting a systematic review in emergency medicine and will help readers appraise the findings of systematic reviews.
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ItemEffect of Fluid Bolus Therapy on Extravascular Lung Water Measured by Lung Ultrasound in Children With a Presumptive Clinical Diagnosis of Sepsis(WILEY, 2019-06)OBJECTIVES: Fluid bolus therapy for the treatment of sepsis may lead to the accumulation of extravascular lung water (EVLW) and result in respiratory dysfunction. We aimed to assess changes in EVLW using lung ultrasound (US) in children with a presumptive clinical diagnosis of sepsis after fluid bolus therapy and correlate these changes with respiratory signs. METHODS: This work was a prospective observational study set in the emergency department of the Royal Children's Hospital. Children meeting international consensus criteria for sepsis receiving fluid bolus therapy were included. Respiratory signs were recorded, and lung US examinations were performed immediately before, 5 minutes after, and 60 minutes after fluid bolus therapy. A pediatric emergency physician blinded to the participants' identities and timing of US calculated an EVLW score from lung US. Results-Fifty fluid boluses were recorded in 41 children. The lung US score (range, 0-8) increased over the study period: median, 1 (interquartile range, 0-2) before fluid bolus therapy, 1 (interquartile range, 0-3) 5 minutes after fluid bolus therapy, and 3 (interquartile range, 1-4) 60 minutes after fluid bolus therapy. Respiratory effort, but not the respiratory rate or the presence of rales, increased over the study period and was correlated with the lung US score (ρ = 0.33; P = .02). CONCLUSIONS: Extravascular lung water as measured by lung US increased after fluid bolus therapy in septic children and was correlated with an increase in the respiratory distress score. The respiratory rate and the presence of rales did not change over the study period. The role of lung US for titrating fluid bolus therapy in sepsis warrants further investigation.
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ItemDoes respiratory variation of inferior vena cava diameter predict fluid responsiveness in spontaneously ventilating children with sepsis(WILEY, 2018-08)OBJECTIVE: The intent of fluid bolus therapy (FBT) is to increase cardiac output and tissue perfusion, yet only 50% of septic children are fluid responsive. We evaluated respiratory variation of inferior vena cava (IVC) diameter as a predictor of fluid responsiveness. METHODS: A prospective observational study in the ED of The Royal Children's Hospital, Melbourne, Australia. Patients were spontaneously ventilating children treated with FBT for sepsis-induced acute circulatory failure. IVC ultrasound was performed prior to FBT. Trans-thoracic echocardiography was performed prior to, 5 and 60 min after FBT. IVC collapsibility index and stroke distance were calculated by a blinded Paediatric Emergency Physician and blinded Paediatric Cardiologist, respectively. RESULTS: Thirty-nine fluid boluses were recorded in 33 children, 28/39 (72%) of which met criteria for fluid responsiveness at 5 min, which was sustained in 2/28 (7%) of initial fluid responders at 60 min. Sensitivity and specificity (95% confidence interval) of IVC collapsibility index were 0.44 (0.25-0.65) and 0.33 (0.10-0.65) with an area under the receiver operator characteristics curve (95% confidence interval) of 0.38 (0.23-0.55) at 5 min. Test characteristics 60 min after fluid bolus administration were not meaningful because of the infrequency of sustained fluid responsiveness in this patient group. There was no significant correlation between IVC collapsibility and fluid responsiveness at 5 or 60 min. CONCLUSIONS: IVC collapsibility has poor test characteristics for predicting fluid responsiveness in spontaneously ventilating children with sepsis.
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ItemThe challenge of infrequency(WILEY, 2021-03)
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ItemFebrile children in the Emergency Department: Frequency and predictors of poor outcome(WILEY, 2021-03)AIM: To evaluate the frequency and predictors of poor outcome in febrile children presenting to the Emergency Department. METHODS: Retrospective observational study from the Emergency Department of The Royal Children's Hospital, Melbourne, Australia. All children with presenting complaint of fever or triage temperature >38°C over a 6-month period were included. Poor outcome was defined as: new organ dysfunction or the requirement for organ support therapy (inotrope infusion, mechanical ventilation, renal replacement therapy and extra-corporeal life support). Predictors evaluated were as follows: initial vital signs, blood tests and clinical scores. Odds ratio, sensitivity, specificity and area under the receiver-operating characteristics curve were calculated for each predictor variable. RESULTS: Between Jan-June 2019, 6217 children met inclusion criteria. Twenty-seven (0.4%) developed new organ dysfunction, 10 (0.2%) required organ support therapy (inotrope infusion in 5, mechanical ventilation in 6, renal replacement therapy in 1, extra-corporeal life support in 1). Odds of new organ dysfunction, requirement for inotropic support and mechanical ventilation were higher with abnormal initial vital signs, blood tests and clinical scores, though overall test characteristics were poor due to infrequency. CONCLUSION: Poor outcomes were uncommon among febrile children presenting to the Emergency Department. Vital signs, blood tests and clinical scores were poor predictors.
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ItemIntubation practices for children in emergency departments and intensive care units across Australia and New Zealand: A survey of medical staff(WILEY, 2020-12)OBJECTIVE: Intubation of children in the emergency setting is a high-risk, low incidence event. Standardisation of clinical practice has been hampered by a lack of high-quality evidence to support one technique over another. The aim of the present study is to determine clinician preference in intubation practice of children in EDs and ICUs in Australia and New Zealand to provide baseline information to allow future targeted research focused on improving the safety and efficacy of paediatric emergency airway management. METHODS: The present study was a voluntary questionnaire undertaken by medical staff at registrar level or above in EDs and ICUs associated with the Paediatric Research in Emergency Departments International Collaborative (PREDICT) and Australia and New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG) research networks. Respondents reported on their individual intubation practices, with a focus on pre-oxygenation and apnoeic oxygenation techniques, and the use of video laryngoscopy. RESULTS: A total of 502 clinicians were invited to complete the survey between May and October 2018 with 336 (66.9%) responded. There was marked variation in practice between ED clinicians and ICU clinicians in the techniques used for pre-oxygenation, the frequency of use of apnoeic oxygenation and the reported use of video laryngoscopy. CONCLUSIONS: Within Australia and New Zealand there is considerable variation in paediatric emergency airway clinical practice, in particular with respect to pre-oxygenation, apnoeic oxygenation and use of video laryngoscopy. Definitive clinical trials are required to best inform clinical practice in this area.