Amplitude Integrated Electroencephalography: Simulated Assessment of Neonatal Seizure Detection in PICU Patients.

OBJECTIVES: Amplitude integrated electroencephalography (aEEG) is a mainstay of care in neonatal ICUs; however, knowledge gaps exist in relation to its accuracy for identifying seizures in older children. We aimed to review the diagnostic accuracy of existing neonatal seizure detection criteria for seizure detection in older children in hospital. DESIGN: Retrospective study. SETTING: PICU/Neurophysiology Department in Dublin. PATIENTS: One hundred twenty patients (2 mo to 16 yr old) were chosen from a database of formal 10-20 system, 21-lead electroencephalography recordings (2012-2020), comprising 30 studies with seizures, 90 without. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electroencephalography studies containing electrographic seizures (ESzs) were annotated to describe number, duration, distribution, and spread. Two-channel aEEG (using leads C3-P3, C4-P4) recordings were generated and independently reviewed by a professional specialist in clinical neurophysiology blinded to outcome and without reference to the raw electroencephalography trace. Logistic regression was used to identify factors associated with correct seizure identification on aEEG. Median patient age was 6.1 years. Abnormal recordings featured 123 seizures. Status epilepticus (SE) was evident by electroencephalography in 10 cases. Using neonatal criteria, aEEG had a sensitivity of 70% and negative predictive value of 90% for identifying any ESz. Accurate detection of individual seizures was diminished when seizures were very short or occurred during waking. Sensitivity for individual seizures was 81% when seizures less than 1 minute were excluded. aEEG correctly identified SE in 70% of the 10 cases, although ESz were confirmed to be present in 80% of this subpopulation. CONCLUSIONS: aEEG criteria for neonatal seizure identification can be applied with caution to older children and should be supplemented by formal electroencephalography. Seizure identification is better for longer seizures and those arising from sleep. SE is not always recognized by aEEG among older children.

Amplitude integrated electroencephalography - Reference values in children aged 2 months to 16 years.

AIM: Amplitude integrated electroencephalography (aEEG) is a bedside neuromonitoring tool, standard within neonatal critical care provision. Its application in children is increasing but normative data underpinning such use are lacking. We present a dataset of normative aEEG values for children aged 2 months to 16 years. METHODS: This retrospective observational cohort study derives aEEG normative amplitude characteristics from electroencephalograms (EEGs) recorded in Children's Health Ireland at Crumlin. aEEG was derived from 350 normal EEGs, recorded in children aged 2 months to 16 years. Supplementary aEEGs were derived from children with abnormal EEG traces. Median upper and lower margin amplitudes and bandwidth were calculated from 5 min waking and sleeping EEG epochs. RESULTS: aEEG amplitudes vary with age and state, increasing over the first 2 years of life before diminishing. Upper and lower margin amplitudes and bandwidth are greater during sleep for children <6 years. Reference ranges may be cohorted into two groups (upper and lower reference limits; <6 years - 38 µV/7 µV awake, 54 µV/10 µV asleep; >6 years - 33 µV/5 µV awake, 36 µV/6 µV asleep). CONCLUSION: aEEG traces evolve with age in childhood and differ from neonatal values. We provide a comprehensive set of aEEG normatives to facilitate clinical interpretation in older children.

Initiating technology dependence to sustain a child's life: a systematic review of reasons.

BACKGROUND: Decision-making in initiating life-sustaining health technology is complex and often conducted at time-critical junctures in clinical care. Many of these decisions have profound, often irreversible, consequences for the child and family, as well as potential benefits for functioning, health and quality of life. Yet little is known about what influences these decisions. A systematic review of reasoning identified the range of reasons clinicians give in the literature when initiating technology dependence in a child, and as a result helps determine the range of influences on these decisions. METHODS: Medline, EMBASE, CINAHL, PsychINFO, Web of Science, ASSIA and Global Health Library databases were searched to identify all reasons given for the initiation of technology dependence in a child. Each reason was coded as a broad and narrow reason type, and whether it supported or rejected technology dependence. RESULTS: 53 relevant papers were retained from 1604 publications, containing 116 broad reason types and 383 narrow reason types. These were grouped into broad thematic categories: clinical factors, quality of life factors, moral imperatives and duty and personal values; and whether they supported, rejected or described the initiation of technology dependence. The majority were conceptual or discussion papers, less than a third were empirical studies. Most discussed neonates and focused on end-of-life care. CONCLUSIONS: There is a lack of empirical studies on this topic, scant knowledge about the experience of older children and their families in particular; and little written on choices made outside 'end-of-life' care. This review provides a sound basis for empirical research into the important influences on a child's potential technology dependence.

Autopsy and pre-mortem diagnostic discrepancy review in an Irish tertiary PICU.

Our study had two objectives: (1) to review ante- and post-mortem diagnoses and assign a Goldman error classification and (2) establish autopsy rates within our centre. We performed a retrospective analysis of autopsies performed on patients who died in our paediatric intensive care unit (PICU) between November 13, 2012, and October 31, 2018. Medical and autopsy data of all patients was reviewed, and Goldman classification of discrepancy between ante- and post-mortem diagnoses was assigned. Our centre is a tertiary PICU, and we included all patients that died in PICU within the designated timeframe. Our results were as follows: 396 deaths occurred in PICU from 8329 (4.75%) admissions. Ninety-nine (25%) had an autopsy, 75 required by the coroner. All were included in the study. Fifty-three were male and 46 females. Fifty-three patients were transferred from external hospitals, 46 from our centre. Forty-one were neonates, 32 were < 1 year of age, and 26 were > 1 year of age. The median length of stay was 3 days. Eighteen were post-cardiac surgery, and three post-cardiac catheter procedure. Major diagnostic errors (class I/II) were identified in 14 (14.1%), 2 (2%) class I, and 12 (12.1%) were class II errors. Class III and IV errors occurred in 28 (28.2%) patients. Complete concordance (class V) occurred in 57 (57.5%) cases.Conclusion: We conclude that the autopsy rate and the diagnostic discrepancy rate within our PICU are comparable to those previously reported. Our findings show the continuing value of autopsy in determining the cause of death and providing greater diagnostic clarity. Given their value, post-mortem examinations, where indicated, should be considered part of a physician's duty of care to families and future patients. What is Known: • Major diagnostic discrepancies (class I/II) in PICU have been reported at 20.2%. (10) • PICU autopsy rates have varied from 36 to 67% since 1994 with most recently reported rates in 2018 being 36%. (6-9) What is New: • We report an Irish PICU major diagnostic discrepancy (class I/II) rates of 14.1% contributing further to reported discrepancy rates in PICU literature to date. • This study contributes the Irish PICU post-mortem rate in a tertiary centre which was 25% over an almost 6-year period.

EEG in the Pediatric Intensive Care Unit: An Irish Experience.

INTRODUCTION: Evidence for continuous EEG monitoring in the pediatric intensive care unit (PICU) is increasing. However, 24/7 access to EEG is not routinely available in most centers, and clinical management is often informed by more limited EEG resources. The experience of EEG was reviewed in a tertiary PICU where 24/7 EEG cover is unavailable. METHODS: Retrospective EEG and clinical review of 108 PICU patients. Correlations were carried out between EEG and clinical variables including mortality. The role of EEG in clinical decision making was documented. RESULTS: One hundred ninety-six EEGs were carried out in 108 PICU patients over 2.5 years (434 hours of recording). After exclusion of 1 outlying patient with epileptic encephalopathy, 136 EEGs (median duration, 65 minutes; range, 20 minutes to 4 hours 40 minutes) were included. Sixty-two patients (57%) were less than 12 months old. Seizures were detected in 18 of 107 patients (17%); 74% of seizures were subclinical; 72% occurred within the first 30 minutes of recording. Adverse EEG findings were associated with high mortality. Antiepileptic drug use was high in the studied population irrespective of EEG seizure detection. Prevalence of epileptiform discharges and EEG seizures diminished with increasing levels of sedation. CONCLUSIONS: EEG provides important diagnostic information in a large proportion of PICU patients. In the absence of 24/7 EEG availability, empirical antiepileptic drug utilization is high.

A systematic concept analysis of 'technology dependent': challenging the terminology.

There are an increasing number of children who are dependent on medical technology to sustain their lives. Although significant research on this issue is taking place, the terminology used is variable and the concept of technology dependence is ill-defined. A systematic concept analysis was conducted examining the attributes, antecedents, and consequences of the concept of technology dependent, as portrayed in the literature. We found that this concept refers to a wide range of clinical technology to support biological functioning across a dependency continuum, for a range of clinical conditions. It is commonly initiated within a complex biopsychosocial context and has wide ranging sequelae for the child and family, and health and social care delivery.Conclusion: The term technology dependent is increasingly redundant. It objectifies a heterogenous group of children who are assisted by a myriad of technology and who adapt to, and function with, this assistance in numerous ways. What is Known: • There are an increasing number of children who require medical technology to sustain their life, commonly referred to as technology dependent. This concept analysis critically analyses the relevance of the term technology dependent which is in use for over 30 years. What is New: • Technology dependency refers to a wide range of clinical technology to support biological functioning across a dependency continuum, for a range of clinical conditions. It is commonly initiated within a complex biopsychosocial context and has wide-ranging sequelae for the child and family, and health and social care delivery. • The paper shows that the term technology dependent is generally portrayed in the literature in a problem-focused manner. • This term is increasingly redundant and does not serve the heterogenous group of children who are assisted by a myriad of technology and who adapt to, and function with, this assistance in numerous ways. More appropriate child-centred terminology will be determined within the TechChild project.

Pediatric Intensive Care: Immunomodulation With Activated Protein C ex vivo.

Objective: Sepsis is major cause of morbidity and mortality in the Pediatric Intensive Care Unit (PICU). PICU patients may develop transient immune deficiency during sepsis. Activated Protein C (APC) has significant anti-inflammatory and cytoprotective effects. Clinical trials of APC in adult sepsis initially showed improved outcome but recent trials showed no benefit in adults or children. We aimed to assess the effects of APC treatment on innate immune responses in children. Design and Subjects: We compared neutrophil and monocyte responses to lipopolysaccharide (LPS) with and without APC treatment in PICU patients at the time of evaluation for sepsis compared with healthy adults and age-matched pediatric controls. We used flow cytometry to examine cell activation (CD11b expression), function [intracellular reactive oxygen intermediate (ROI) release] and LPS recognition [Toll like Receptor 4 (TLR4) expression]. Results: PICU patients had significantly decreased protein c levels and LPS responses compared with adult and pediatric controls for all parameters. APC reduced LPS-induced neutrophil PICU TLR4 and adult ROI (p < 0.05). PICU non-survivors had increased LPS induced neutrophil and monocyte ROI production vs. survivors which was significantly reduced by APC. Conclusion: PICU patients demonstrate significantly reduced endotoxin reactivity which may predispose them to sepsis and alter effective antibacterial responses. APC reduces LPS-induced ROI production in adults and may have a role in treating severely compromised PICU patients especially given that newer APC forms are associated with decreased bleeding risk and enhanced anti-inflammatory effects.

Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study.

BACKGROUND: Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilized in clinical practice and in research studies. Within these studies, clonidine has inconsistently shown useful sedation properties. One of the reasons attributed to the inconsistent signs of efficacy is suboptimal clonidine dosing. AIMS: This study aims to propose a target plasma concentration and simulate clonidine pharmacokinetics (PK) in a cohort of mechanically ventilated children to evaluate the adequacy of clonidine dosage regimens used in clinical practice and research studies. METHODS: A literature search was undertaken to identify a clonidine pharmaockinetic-pharmacodynamics (PKPD) model, from which a target concentration for sedation was defined. Using a previously published PK model, the projected plasma concentrations of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed. RESULTS: A target plasma concentration of above 2 µg/L was proposed. Nine dosage regimens (four intravenous boluses, four intravenous infusions, and one nasogastric route boluses) were evaluated ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Regimens with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score appear most suitable. Doses should be halved in neonates. CONCLUSION: The variety of dosage regimens in the previous studies of clonidine along with difficulties in the conduct of interventional studies may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by higher than current practice maintenance dose infusion is required to achieve adequate steady-state concentrations early in treatment. Further PKPD studies will aid in the determination of the optimal clonidine dosage regimen.

The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study.

OBJECTIVES: There is limited evidence supporting the widespread use of α2 agonists (clonidine and dexmedetomidine) in pediatric critical care sedation. This study sought to test the association between the use of α2 agonists and enhanced sedation. DESIGN: A retrospective observational cohort study was conducted. Noninferiority of time adequately sedated (COMFORT Behavior Score 11-16) while mechanically ventilated was assessed. Secondarily, dosing of opioids and benzodiazepines was examined. SETTING: Two tertiary PICUs. PATIENTS: Children were classified into an exposed group, who received an α2 agonist as part of their sedation regimen, and an unexposed group. Groups were matched using propensity score analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand eighty-five patients were included. The exposed group were adequately sedated 74% (95% CI, 72-75%) of the study time compared with the unexposed group at 70% (95% CI, 67-72%) giving a ratio of 1.06 (95% CI, 1.02-1.10) and a noninferior time adequately sedated. A decrease in time oversedated was observed with 8.1% (95% CI, 4.3-11.9%) less time classified as oversedated in the exposed group. Reduction in morphine use of 0.25 µg/kg/hr (95% CI, -0.68 to 1.18 µg/kg/hr) was not statistically significant. Midazolam use did not decrease and was statistically higher. CONCLUSIONS: Use of α2 agonists was associated with similar time adequately sedated as a matched unexposed group although no reduction in morphine or benzodiazepine coadministration was observed. There was a shift toward lighter sedation with α2 agonist use.

A retrospective observational study of acquired subglottic stenosis using low-pressure, high-volume cuffed endotracheal tubes.

INTRODUCTION: The safety of cuffed endotracheal tubes in the neonatal and critically ill pediatric population continues to be questioned due to the theoretical risk of acquired subglottic stenosis. The incidence of acquired subglottic stenosis in the high-risk mixed surgical and medical critically ill pediatric cohort using high-volume, low-pressure cuffed endotracheal tube policy has not yet been described. The aim of our study was to describe and evaluate the use and complication rate of cuffed ETT's in our unit over a 5-year period. METHODS: We defined clinically significant subglottic stenosis as a positive stenotic finding of endotracheal tube-related pathology on a microlaryngoscopy within 6 months of invasive ventilation. All patients admitted through our pediatric critical care unit from January 10, 2012 to January 25, 2017 were matched against our theater management system database for the same period. We reviewed all matching patients' baseline demographics, comorbidities, intubation/endotracheal tube history, and subsequent surgical management. RESULTS: Of 5309 pediatric critical care unit admissions (61% ventilated) and 1251 microlaryngoscopies, 23 children had endoscopic findings of clinically significant endotracheal tube-related pathology, reflecting 0.68% of all intubated patients. Eight patients developed acquired subglottic stenosis. All those requiring major surgical correction were ex-premature neonates initially intubated with uncuffed tubes in an external neonatal intensive care. No patient initially intubated with a cuffed endotracheal tube developed subglottic stenosis requiring surgical correction. CONCLUSION: We report no single case of acquired subglottic stenosis in our cohort that required major surgical correction from a cuffed endotracheal tube during a 5-year period. The introduction of a policy of appropriate placement and maintenance of low-pressure, high-volume cuffed endotracheal tubes in the pediatric critical care unit was not associated with an increased rate of endotracheal tube-related subglottic trauma.

Effectiveness of α2agonists for sedation in paediatric critical care: study protocol for a retrospective cohort observational study.

INTRODUCTION: Mechanically ventilated children in paediatric intensive care units are commonly administered analgesics and sedative agents to minimise pain and distress and facilitate cooperation with medical interventions. Opioids and benzodiazepines are the most common analgesic and sedative agents but have safety concerns. The α2 agonists clonidine and dexmedetomidine are alternative sedatives in use despite neither having robust evidence to support their use. Studies evaluating effectiveness of α2 agonists to date have not focused on sedation-based outcomes instead focusing on opioid-sparing properties and ventilation outcomes. The aim of this study is to evaluate if an opioid-based sedation regimen, with an α2 agonist adjunct (clonidine or dexmedetomidine), produces a non-inferior proportion of time adequately sedated compared with a control group without an α2 agonist adjunct, while conferring potential additional benefits such as reduced opioid administration and less exposure to potential additional agents such as benzodiazepines. METHODS AND ANALYSIS: We will conduct a retrospective cohort study in two Irish paediatric intensive care units using clinical information on patient characteristics, sedation scores and drug use. Eligible children admitted between January 2014 and June 2016 who were mechanically ventilated and received an opioid infusion will be included. Patients will be categorised into two exposure categories (received an α2 agonist or did not receive an α2 agonist) and the time adequately sedated (measured using the COMFORT Behaviour Score) will be calculated using interpolation of nursing sedation scores at each recorded time point. At least 150 per group is planned for inclusion to ensure adequate study power. Propensity score matching will be used in analysis to account for potential confounding by indication. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of both hospitals. Dissemination will occur via local, national and international presentations for academic and healthcare audiences as well as through peer reviewed publications.

Efficacy of α2-Agonists for Sedation in Pediatric Critical Care: A Systematic Review.

OBJECTIVE: Children in PICUs normally require analgesics and sedatives to maintain comfort, safety, and cooperation with interventions. α2-agonists (clonidine and dexmedetomidine) have been described as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. This systematic review aimed to determine whether α2-agonists were effective in maintaining patients at a target sedation score over time compared with a comparator group. We also aimed to determine whether concurrent use of α2-agonists provided opioid-sparing effects. DATA SOURCES: A systematic search was performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, and LILACS. STUDY SELECTION: We included randomized controlled trials of children in PICU treated with clonidine or dexmedetomidine for the indication of sedation. DATA EXTRACTION: Two authors independently screened articles for inclusion. DATA SYNTHESIS: Six randomized controlled trials with sufficient data were identified and critically appraised. Three clonidine trials (two vs placebo and one vs midazolam) and three dexmedetomidine trials (two vs fentanyl, one vs midazolam) were included. Due to study heterogeneity it was not possible to pool studies. A narrative synthesis is provided. CONCLUSIONS: Reporting of study results using the outcome "time maintained at target sedation score' for clonidine or dexmedetomidine was poor. Only one trial compared clonidine with midazolam using a sedation score outcome. This study was underpowered to demonstrate equivalence to midazolam as a sedative. The adjunctive use of clonidine demonstrated significant decreases in opioid use in neonates but not in older groups. Clonidine dose was inconsistent between studies. Dexmedetomidine demonstrated an opioid-sparing effect in two small trials. Further studies, including dose-finding studies and studies with sedation score-based outcomes, are needed.

A prospective crossover comparison of neurally adjusted ventilatory assist and pressure-support ventilation in a pediatric and neonatal intensive care unit population.

OBJECTIVE: To compare neurally adjusted ventilatory assist ventilation with pressure-support ventilation. DESIGN: Prospective, crossover comparison study. SETTING: Tertiary care pediatric and neonatal intensive care unit. PATIENTS: Sixteen ventilated infants and children: mean age = 9.7 months (range = 2 days-4 yrs) and mean weight = 6.2 kg (range = 2.4-13.7kg). INTERVENTIONS: A modified nasogastric tube was inserted and correct positioning was confirmed. Patients were ventilated in pressure-support mode with a pneumatic trigger for a 30-min period and then in neurally adjusted ventilatory assist mode for up to 4 hrs. MEASUREMENTS AND MAIN RESULTS: Data collected for comparison included activating trigger (neural vs. pneumatic), peak and mean airway pressures, expired minute and tidal volumes, heart rate, respiratory rate, pulse oximetry, end-tidal CO2 and arterial blood gases. Synchrony was improved in neurally adjusted ventilatory assist mode with 65% (+/-21%) of breaths triggered neurally vs. 35% pneumatically (p < .001) and 85% (+/-8%) of breaths cycled-off neurally vs. 15% pneumatically (p = .0001). The peak airway pressure in neurally adjusted ventilatory assist mode was significantly lower than in pressure-support mode with a 28% decrease in pressure after 30 mins (p = .003) and 32% decrease after 3 hrs (p < .001). Mean airway pressure was reduced by 11% at 30 mins (p = .13) and 9% at 3 hrs (p = .31) in neurally adjusted ventilatory assist mode although this did not reach statistical significance. Patient hemodynamics and gas exchange remained stable for the study period. No adverse patient events or device effects were noted. CONCLUSIONS: In a neonatal and pediatric intensive care unit population, ventilation in neurally adjusted ventilatory assist mode was associated with improved patient-ventilator synchrony and lower peak airway pressure when compared with pressure-support ventilation with a pneumatic trigger. Ventilating patients in this new mode seem to be safe and well tolerated.