Use of Intraosseous Access in Neonatal and Pediatric Retrieval-Neonatal and Pediatric Emergency Transfer Service, New South Wales.

OBJECTIVES: Pediatric patients who are critically unwell require rapid access to central vasculature for administration of life-saving medications and fluids. The intraosseous (IO) route is a well-described method of accessing the central circulation. There is a paucity of data surrounding the use of IO in neonatal and pediatric retrieval. The aim of this study was to review the frequency, complications, and efficacy of IO insertion in neonatal and pediatric patients in retrieval. METHODS: A retrospective review of cases referred to neonatal and pediatric emergency transfer service, New South Wales over the epoch 2006 to 2020. Medical records documenting IO use were audited for patient demographic data, diagnosis, treatment details, IO insertion and complication statistics, and mortality data. RESULTS: Intraosseous access was used in 467 patients (102 neonatal/365 pediatric). The most common indications were sepsis, respiratory distress, cardiac arrest, and encephalopathy. The main treatments were fluid bolus, antibiotics, maintenance fluids, and resuscitation drugs. Return of spontaneous circulation after resuscitation drugs occurred in 52.9%; perfusion improved with fluid bolus in 73.1%; blood pressure improved with inotropes in 63.2%; seizures terminated with anticonvulsants in 88.7%. Prostaglandin E1 was given to eight patients without effect. Intraosseous access-related injury occurred in 14.2% of pediatric and 10.8% of neonatal patients. Neonatal and pediatric mortality rates were 18.6% and 19.2%, respectively. CONCLUSIONS: Survival in retrieved neonatal and pediatric patients who required IO is higher than previously described in pediatric and adult cohorts. Early insertion of an IO facilitates early volume expansion, delivery of critical drugs, and allows time for retrieval teams to gain more definitive venous access. In this study, prostaglandin E1 delivered via a distal limb IO had no success in reopening the ductus arteriosus.

Continuous local anaesthetic wound infusion of bupivacaine for postoperative analgesia in neonates: a randomised control trial (CANWIN Study).

OBJECTIVE: To determine the effect of continuous wound infusion of local anaesthetic drug (bupivacaine) on total amount of systemic opioid use in the first 72 hours in newborn infants undergoing laparotomy. DESIGN: A two-arm parallel, open-label randomised controlled trial. SETTING: A quaternary newborn intensive care unit. PATIENTS: Infants>37 weeks of gestation undergoing laparotomy for congenital or acquired abdominal conditions. INTERVENTIONS: Continuous wound infusion of local anaesthetic (bupivacaine) for the first 72 hours along with systemic opioid analgesia (catheter group) or only systemic opioid analgesia (opioid group). MAIN OUTCOME: Total amount of systemic opioid used within the first 72 hours post laparotomy. RESULTS: The study was underpowered as only 30 of the expected sample size of 70 infants were enrolled. 16 were randomised to catheter group and 14 to opioid group. The two groups were similar at baseline. There was no significant difference between the groups for the primary outcome of median total systemic opioid use in the first 72 hours post laparotomy (catheter 431.5 µg/kg vs opioid 771 µg/kg, difference -339.5 µg/kg, 90% CIhigh 109, p value 0.28). There was no significant difference between the groups for any of the secondary outcomes including pain scores, duration of mechanical ventilation, time to reach full feeds and duration of hospital stay. There were no adverse events noted. CONCLUSION: Continuous wound infusion of local anaesthetic along with systemic opioid analgesia is feasible. The lack of a difference in total systemic opioid use in the first 72 hours cannot be reliably interpreted as the study was underpowered. TRIAL REGISTRATION NUMBER: ACTRN12610000633088.

The practice of blood volume submitted for culture in a neonatal intensive care unit.

BACKGROUND: Neonatal sepsis is the leading cause of mortality and morbidity in neonatal intensive care units. The volume of blood taken for culture remains one of the most important factors in isolating microorganisms. OBJECTIVES: To evaluate the impact of the intervention on the blood volume submitted for culture and to identify factors influencing the volume as determined by the phlebotomist. METHODS: Blood culture volume was determined by weighing the culture bottle before and immediately after blood inoculation. A 3-month preintervention audit revealed that in 126/130 samples (96.9%), the volume of blood submitted was suboptimal. Multiple intervention measures were instituted, and volume was monitored over the next 9 months. RESULTS: 637 blood culture samples were included in the study, 130 were in preintervention and 507 were in postintervention epochs. Following the intervention, suboptimal volume samples reduced from 96.9% (126/130 samples) to 25% (126/507 samples), p<0.0001 and the median (IQR) sample volume improved from 0.36 (0.23) ml to 0.9 (0.27) ml, p<0.0001. Poor blood flow was identified as the most common reason for an inadequate sample. CONCLUSION: The study underscores the role of educational intervention in improving the blood culture volume in newborn infants. Poor backflow from the cannula is an important cause of inadequate volume collection.

Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders.

Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalization of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with bilateral basal ganglia abnormalities on brain MRI was undertaken in this international multicentre cohort study. Three hundred and five MRI scans belonging to 201 children with 34 different disorders were rated using a standard radiological scoring proforma. In addition, literature review on MRI patterns was undertaken in these 34 disorders and 59 additional disorders reported with bilateral basal ganglia MRI abnormalities. Cluster analysis on first MRI findings from the study cohort grouped them into four clusters: Cluster 1-T2-weighted hyperintensities in the putamen; Cluster 2-T2-weighted hyperintensities or increased MRI susceptibility in the globus pallidus; Cluster 3-T2-weighted hyperintensities in the globus pallidus, brainstem and cerebellum with diffusion restriction; Cluster 4-T1-weighted hyperintensities in the basal ganglia. The 34 diagnostic categories included in this study showed dominant clustering in one of the above four clusters. Inflammatory disorders grouped together in Cluster 1. Mitochondrial and other neurometabolic disorders were distributed across clusters 1, 2 and 3, according to lesions dominantly affecting the striatum (Cluster 1: glutaric aciduria type 1, propionic acidaemia, 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome and thiamine responsive basal ganglia disease associated with SLC19A3), pallidum (Cluster 2: methylmalonic acidaemia, Kearns Sayre syndrome, pyruvate dehydrogenase complex deficiency and succinic semialdehyde dehydrogenase deficiency) or pallidum, brainstem and cerebellum (Cluster 3: vigabatrin toxicity, Krabbe disease). The Cluster 4 pattern was exemplified by distinct T1-weighted hyperintensities in the basal ganglia and other brain regions in genetically determined hypermanganesemia due to SLC39A14 and SLC30A10. Within the clusters, distinctive basal ganglia MRI patterns were noted in acquired disorders such as cerebral palsy due to hypoxic ischaemic encephalopathy in full-term babies, kernicterus and vigabatrin toxicity and in rare genetic disorders such as 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome, thiamine responsive basal ganglia disease, pantothenate kinase-associated neurodegeneration, TUBB4A and hypermanganesemia. Integrated findings from the study cohort and literature review were used to propose a diagnostic algorithm to approach bilateral basal ganglia abnormalities on MRI. After integrating clinical summaries and MRI findings from the literature review, we developed a prototypic decision-making electronic tool to be tested using further cohorts and clinical practice.

Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis.

BACKGROUND: Despite the discovery of CSF and serum diagnostic autoantibodies in autoimmune encephalitis, there are still very limited CSF biomarkers for diagnostic and monitoring purposes in children with inflammatory or autoimmune brain disease. The cause of encephalitis is unknown in up to a third of encephalitis cohorts, and it is important to differentiate infective from autoimmune encephalitis given the therapeutic implications. AIM: To study CSF cytokines and chemokines as diagnostic biomarkers of active neuroinflammation, and assess their role in differentiating demyelinating, autoimmune, and viral encephalitis. METHODS: We measured and compared 32 cytokine/chemokines using multiplex immunoassay and APRIL and BAFF using ELISA in CSF collected prior to commencing treatment from paediatric patients with confirmed acute disseminated encephalomyelitis (ADEM, n = 16), anti-NMDAR encephalitis (anti-NMDAR E, n = 11), and enteroviral encephalitis (EVE, n = 16). We generated normative data using CSF from 20 non-inflammatory neurological controls. The sensitivity of CSF cytokine/chemokines to diagnose encephalitis cases was calculated using 95th centile of control values as cut off. We correlated CSF cytokine/chemokines with disease severity and follow up outcome based on modified Rankin scale. One-way hierarchical correlational cluster analysis of molecules was performed in different encephalitis and outcome groups. RESULTS: In descending order, CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 had the best sensitivity (>79.1%) when all encephalitis patients were included. The combination of IL-6 and IFN-α was most predictive of inflammation on multiple logistic regression with area under the ROC curve 0.99 (CI 0.97-1.00). There were no differences in CSF cytokine concentrations between EVE and anti-NMDAR E, whereas ADEM showed more pronounced elevation of Th17 related (IL-17, IL-21) and Th2 (IL-4, CCL17) related cytokine/chemokines. Unlike EVE, heat map analysis showed similar clustering of cytokine/chemokine molecules in immune mediated encephalitis (ADEM and anti-NMDAR E). Th1 and B cell (CXCL13 and CXCL10) molecules clustered together in patients with severe encephalopathy at admission and worse disability at follow up in all encephalitis. There was no correlation between CSF neopterin and IFN-γ or IFN-α. CONCLUSION: A combination panel of cytokine/chemokines consisting of CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 measured using multiplex immunoassay may be used to diagnose and monitor intrathecal inflammation in the brain. Given their association with worse outcome, certain key chemokines (CXCL13, CXCL10) could represent potential therapeutic targets in encephalitis.