| 1. |
- El-Dib, Mohamed, et al.
(författare)
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Neuromonitoring in neonatal critical care part I : neonatal encephalopathy and neonates with possible seizures
- 2023
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Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 94:1, s. 64-73
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Forskningsöversikt (refereegranskat)abstract
- The blooming of neonatal neurocritical care over the last decade reflects substantial advances in neuromonitoring and neuroprotection. The most commonly used brain monitoring tools in the neonatal intensive care unit (NICU) are amplitude integrated EEG (aEEG), full multichannel continuous EEG (cEEG), and near-infrared spectroscopy (NIRS). While some published guidelines address individual tools, there is no consensus on consistent, efficient, and beneficial use of these modalities in common NICU scenarios. This work reviews current evidence to assist decision making for best utilization of neuromonitoring modalities in neonates with encephalopathy or with possible seizures. Neuromonitoring approaches in extremely premature and critically ill neonates are discussed separately in the companion paper. Impact:center dot Neuromonitoring techniques hold promise for improving neonatal care. center dot For neonatal encephalopathy, aEEG can assist in screening for eligibility for therapeutic hypothermia, though should not be used to exclude otherwise eligible neonates. Continuous cEEG, aEEG and NIRS through rewarming can assist in prognostication. center dot For neonates with possible seizures, cEEG is the gold standard for detection and diagnosis. If not available, aEEG as a screening tool is superior to clinical assessment alone. The use of seizure detection algorithms can help with timely seizures detection at the bedside.
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| 2. |
- El-Dib, Mohamed, et al.
(författare)
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Neuromonitoring in neonatal critical care part II : extremely premature infants and critically ill neonates
- 2023
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Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 94:1, s. 55-63
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Forskningsöversikt (refereegranskat)abstract
- Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. Impact For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication. For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury. Continuous multimodal monitoring as well as monitoring of sleep, sleep-wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care.
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| 3. |
- Hellström-Westas, Lena, 1954-, et al.
(författare)
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Systematic review of neonatal seizure management strategies provides guidance on anti-epileptic treatment
- 2015
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 104:2
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Forskningsöversikt (refereegranskat)abstract
- There is a lack of scientific evidence to support the best management of neonatal seizures. Current strategies for neonatal seizure management were investigated by analysis of all surveys published during the time period 2000-2012. Methods for seizure diagnosis and availability of electroencephalogram (EEG), including monitoring, varied. Phenobarbital was the drug of first choice, and the use of off-label drugs and treatment times varied. We conclude that there is an urgent need for more evidence-based studies to guide neonatal seizure management.
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| 4. |
- Palmu, Kirsi, et al.
(författare)
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Detection of 'EEG bursts' in the early preterm EEG : Visual vs. automated detection
- 2010
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 121:7, s. 1015-1022
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the characteristics of activity bursts in the early preterm EEG, to assess inter-rater agreement of burst detection by visual inspection, and to determine the performance of an automated burst detector that uses non-linear energy operator (NLEO). Methods: EEG recordings from extremely preterm (n = 12) and very preterm (n = 6) infants were analysed. Three neurophysiologists independently marked bursts in the EEG, the characteristics of bursts were analyzed and inter-rater agreement determined. Unanimous detections were used as the gold standard in estimating the performance of an automated burst detector. In addition, some details of this automated detector were revised in an attempt to improve performance. Results: Overall, inter-rater agreement was 86% for extremely preterm infants and 81% for very preterm infants. In visual markings, bursts had variable lengths (similar to 1-10 s) and increased amplitudes (and power) throughout the frequency spectrum. Accuracy of the original detection algorithm was 87% and 79% and accuracy of the revised algorithm 93% and 87% for extremely preterm and very preterm babies, respectively. Conclusion: Visual detection of bursts from the early preterm EEG is comparable albeit not identical between raters. The original automated detector underestimates the amount of burst occurrence, but can be readily improved to yield results comparable to visual detection. Further clinical studies are warranted to assess the optimal descriptors of burst detection for monitoring and prognostication. Significance: Validation of a burst detector offers an evidence-based platform for further development of brain monitors in very preterm babies.
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| 5. |
- Pressler, Ronit M., et al.
(författare)
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Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO) : an open-label, dose finding, and feasibility phase 1/2 trial
- 2015
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 14:5, s. 469-477
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Tidskriftsartikel (refereegranskat)abstract
- Background Predinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding, and feasibility phase 1/2 trial, we recruited full-term infants younger than 48 h who had hypoxic ischaemic encephalopathy and electrographic seizures not responding to a loading-dose of phenobarbital from eight neonatal intensive care units across Europe. Newborn babies were allocated to receive an additional dose of phenobarbital and one of four bumetanide dose levels by use of a bivariate Bayesian sequential dose-escalation design to assess safety and efficacy. We assessed adverse events, pharmacokinetics, and seizure burden during 48 h continuous electroencephalogram (EEG) monitoring. The primary efficacy endpoint was a reduction in electrographic seizure burden of more than 80% without the need for rescue antiepileptic drugs in more than 50% of infants. The trial is registered with ClinicalTrials.gov, number NCT01434225. Findings Between Sept 1, 2011, and Sept 28, 2013, we screened 30 infants who had electrographic seizures due to hypoxic ischaemic encephalopathy. 14 of these infants (10 boys) were included in the study (dose allocation: 0.05 mg/kg, n=4; 0.1 mg/kg, n=3; 0. 2 mg/kg, n=6; 0.3 mg/kg, n=1). All babies received at least one dose of bumetanide with the second dose of phenobarbital; three were withdrawn for reasons unrelated to bumetanide, and one because of dehydration. All but one infant also received aminoglycosides. Five infants met EEG criteria for seizure reduction (one on 0.05 mg/kg, one on 0.1 mg/kg and three on 0.2 mg/kg), and only two did not need rescue antiepileptic drugs (ie, met rescue criteria; one on 0.05 mg/kg and one on 0.3 mg/kg). We recorded no short-term dose-limiting toxic effects, but three of 11 surviving infants had hearing impairment confirmed on auditory testing between 17 and 108 days of age. The most common non-serious adverse reactions were moderate dehydration in one, mild hypotension in seven, and mild to moderate electrolyte disturbances in 12 infants. The trial was stopped early because of serious adverse reactions and limited evidence for seizure reduction. Interpretation Our findings suggest that bumetanide as an add-on to phenobarbital does not improve seizure control in newborn infants who have hypoxic ischaemic encephalopathy and might increase the risk of hearing loss, highlighting the risks associated with the off-label use of drugs in newborn infants before safety assessment in controlled trials.
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| 6. |
- Stevenson, Nathan J., et al.
(författare)
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Interobserver agreement for neonatal seizure detection using multichannel EEG
- 2015
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 2:11, s. 1002-1011
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the interobserver agreement (IOA) of neonatal seizure detection using the gold standard of conventional, multichannel EEG. Methods: A cohort of full-term neonates at risk of acute encephalopathy was included in this prospective study. The EEG recordings of these neonates were independently reviewed for seizures by three international experts. The IOA was estimated using statistical measures including Fleiss' kappa and percentage agreement assessed over seizure events (event basis) and seizure duration (temporal basis). Results: A total of 4066 h of EEG recordings from 70 neonates were reviewed with an average of 2555 seizures detected. The IOA was high with temporal assessment resulting in a kappa of 0.827 (95% CI: 0.769-0.865; n = 70). The median agreement was 83.0% (interquartile range [IQR]: 76.6-89.5%; n = 33) for seizure and 99.7% (IQR: 98.9-99.8%; n = 70) for non-seizure EEG. Analysis of events showed a median agreement of 83.0% (IQR: 72.9-86.6%; n = 33) for seizures with 0.018 disagreements per hour (IQR: 0.000-0.090 per hour; n = 70). Observers were more likely to disagree when a seizure was less than 30 sec. Overall, 33 neonates were diagnosed with seizures and 28 neonates were not, by all three observers. Of the remaining nine neonates with contradictory EEG detections, seven presented with low total seizure burden. Interpretation: The IOA is high among experts for the detection of neonatal seizures using conventional, multichannel EEG. Agreement is reduced when seizures are rare or have short duration. These findings support EEG-based decision making in the neonatal intensive care unit, inform EEG interpretation guidelines, and provide benchmarks for seizure detection algorithms.
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| 7. |
- Stevenson, Nathan J., et al.
(författare)
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Treatment Trials for Neonatal Seizures : The Effect of Design on Sample Size
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal seizures are common in the neonatal intensive care unit. Clinicians treat these seizures with several anti-epileptic drugs (AEDs) to reduce seizures in a neonate. Current AEDs exhibit sub-optimal efficacy and several randomized control trials (RCT) of novel AEDs are planned. The aim of this study was to measure the influence of trial design on the required sample size of a RCT. We used seizure time courses from 41 term neonates with hypoxic ischaemic encephalopathy to build seizure treatment trial simulations. We used five outcome measures, three AED protocols, eight treatment delays from seizure onset (T-d) and four levels of trial AED efficacy to simulate different RCTs. We performed power calculations for each RCT design and analysed the resultant sample size. We also assessed the rate of false positives, or placebo effect, in typical uncontrolled studies. We found that the false positive rate ranged from 5 to 85% of patients depending on RCT design. For controlled trials, the choice of outcome measure had the largest effect on sample size with median differences of 30.7 fold (IQR: 13.7-40.0) across a range of AED protocols, Td and trial AED efficacy (p<0.001). RCTs that compared the trial AED with positive controls required sample sizes with a median fold increase of 3.2 ( IQR: 1.9-11.9; p<0.001). Delays in AED administration from seizure onset also increased the required sample size 2.1 fold (IQR: 1.7-2.9; p<0.001). Subgroup analysis showed that RCTs in neonates treated with hypothermia required a median fold increase in sample size of 2.6 (IQR: 2.4-3.0) compared to trials in normothermic neonates (p<0.001). These results show that RCT design has a profound influence on the required sample size. Trials that use a control group, appropriate outcome measure, and control for differences in Td between groups in analysis will be valid and minimise sample size.
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| 8. |
- Toorell, Hanna, et al.
(författare)
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Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy.
- 2024
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Ingår i: Neonatology. - 1661-7819. ; 121:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE.In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers.GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681-0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases.Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III.
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| 9. |
- Vanhatalo, Sampsa, et al.
(författare)
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Why monitor the neonatal brain-that is the important question
- 2023
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Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 93:1, s. 19-21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A key goal of neonatal neurocritical care is improved outcomes, and brain monitoring plays an essential role. The recent NEST trial(1) reported no outcome benefits using aEEG monitoring compared to clinical seizure identification among neonates treated for seizures. However, the study failed to prove the effects of monitoring on seizure treatment in the first place.
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| 10. |
- Weeke, Lauren C., et al.
(författare)
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Lidocaine response rate in aEEG-confirmed neonatal seizures : Retrospective study of 413 full-term and preterm infants
- 2016
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 57:2, s. 233-242
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate the seizure response rate to lidocaine in a large cohort of infants who received lidocaine as second- or third-line antiepileptic drug (AED) for neonatal seizures. MethodsFull-term (n = 319) and preterm (n = 94) infants, who received lidocaine for neonatal seizures confirmed on amplitude-integrated EEG (aEEG), were studied retrospectively (January 1992-December 2012). Based on aEEG findings, the response was defined as good (>4 h no seizures, no need for rescue medication); intermediate (0-2 h no seizures, but rescue medication needed after 2-4 h); or no clear response (rescue medication needed <2 h). ResultsLidocaine had a good or intermediate effect in 71.4%. The response rate was significantly lower in preterm (55.3%) than in full-term infants (76.1%, p < 0.001). In full-term infants the response to lidocaine was significantly better than midazolam as second-line AED (21.4% vs. 12.7%, p = 0.049), and there was a trend for a higher response rate as third-line AED (67.6% vs. 57%, p = 0.086). Both lidocaine and midazolam had a higher response rate as third-line AED than as second-line AED (p < 0.001). Factors associated with a good response to lidocaine were the following: higher gestational age, longer time between start of first seizure and administration of lidocaine, lidocaine as third-line AED, use of new lidocaine regimens, diagnosis of stroke, use of digital aEEG, and hypothermia. Multivariable analysis of seizure response to lidocaine included lidocaine as second- or third-line AED and seizure etiology. SignificanceSeizure response to lidocaine was seen in similar to 70%. The response rate was influenced by gestational age, underlying etiology, and timing of administration. Lidocaine had a significantly higher response rate than midazolam as second-line AED, and there was a trend for a higher response rate as third-line AED. Both lidocaine and midazolam had a higher response rate as third-line compared to second-line AED, which could be due to a pharmacologic synergistic mechanism between the two drugs.
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