Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study.
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ABSTRACT: Objective
To assess the risk factors for electrographic seizures among neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE).Methods
Three-center observational cohort study of 90 term neonates treated with hypothermia, monitored with continuous video-EEG (cEEG) within the first day of life (median age at onset of recording 9.5 hours, interquartile range 6.3-14.5), and continued for >24 hours (total recording 93.3 hours, interquartile range 80.1-112.8 among survivors). A pediatric electroencephalographer at each site reviewed cEEGs for electrographic seizures and initial EEG background category.Results
A total of 43 (48%) had electrographic seizures, including 9 (10%) with electrographic status epilepticus. Abnormal initial EEG background classification (excessively discontinuous, depressed and undifferentiated, burst suppression, or extremely low voltage), but not clinical variables (including pH <6.8, base excess ≤-20, or 10-minute Apgar ≤ 3), was strongly associated with seizures.Conclusions
Electrographic seizures are common among neonates with HIE undergoing hypothermia and are difficult to predict based on clinical features. These results justify the recommendation for cEEG monitoring in neonates treated with hypothermia.
SUBMITTER: Glass HC
PROVIDER: S-EPMC4001204 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTo improve the objective assessment of continuous video-EEG (cEEG) monitoring of neonatal brain function, the aim was to relate automated derived amplitude and duration parameters of the suppressed periods in the EEG background (dynamic Interburst Interval= dIBIs) after neonatal hypoxic-ischemic encephalopathy (HIE) to favourable or adverse neurodevelopmental outcome.MethodsNineteen neonates (gestational age 36-41 weeks) with HIE underwent therapeutic hypothermia and had cEEG-monitoring. EEGs were retrospectively analyzed with a previously developed algorithm to detect the dynamic Interburst Intervals. Median duration and amplitude of the dIBIs were calculated at 1 h-intervals. Sensitivity and specificity of automated EEG background grading for favorable and adverse outcomes were assessed at 6 h-intervals.ResultsDynamic IBI values reached the best prognostic value between 18 and 24 h (AUC of 0.93). EEGs with dIBI amplitude ≥15 μV and duration <10 s had a specificity of 100% at 6-12 h for favorable outcome but decreased subsequently to 67% at 25-42 h. Suppressed EEGs with dIBI amplitude <15 μV and duration >10 s were specific for adverse outcome (89-100%) at 18-24 h (n = 10). Extremely low voltage and invariant EEG patterns were indicative of adverse outcome at all time points.ConclusionsAutomated analysis of the suppressed periods in EEG of neonates with HIE undergoing TH provides objective and early prognostic information. This objective tool can be used in a multimodal strategy for outcome assessment. Implementation of this method can facilitate clinical practice, improve risk stratification and aid therapeutic decision-making. A multicenter trial with a quantifiable outcome measure is warranted to confirm the predictive value of this method in a more heterogeneous dataset.
| S-EPMC6372079 | biostudies-literature
Project description:The objective of this study was to describe the French practice of hypothermia treatment (HT) in full-term newborns with hypoxic-ischemic encephalopathy (HIE) and to analyze the deviations from the guidelines of the French Society of Neonatology.From May 2010 to March 2012 we recorded all cases of HIE treated by HT in a French national database. The population was divided into three groups, "optimal HT" (OHT), "late HT" (LHT) and "non-indicated" HT (NIHT), according to the guidelines.Of the 311 newborns registered in the database and having HT, 65% were classified in the OHT group, 22% and 13% in the LHT and NIHT groups respectively. The severity of asphyxia and HIE were comparable between newborns with OHT and LHT, apart from EEG. HT was initiated at a mean time of 12 hours of life in the LHT group. An acute obstetrical event was more likely to be identified among newborns with LHT (46%), compared to OHT (34%) and NIHT (22%). There was a gradation in the rate of complications from the NIHT group (29%) to the LHT (38%) group and the OHT group (52%). Despite an insignificant difference in the rates of death or abnormal neurological examination at discharge, nearly 60% of newborns in the OHT group had an MRI showing abnormalities, compared to 44% and 49% in the LHT and NIHT groups respectively.The conduct of the HT for HIE newborns is not consistent with French guidelines for 35% of newborns, 22% being explained by an excessive delay in the start of HT, 13% by the lack of adherence to the clinical indications. This first report illustrates the difficulties in implementing guidelines for HT and should argue for an optimization of perinatal care for HIE.
| S-EPMC3877096 | biostudies-other
Project description:ObjectiveWe evaluated the impact of monitoring indication, early electroencephalography (EEG), and clinical features on seizure risk in all neonates undergoing continuous EEG (cEEG) monitoring following a standardized monitoring protocol.MethodsAll cEEGs from unique neonates 34-48 weeks postmenstrual age monitored from 1/2011-10/2017 (n = 291) were included. We evaluated the impact of cEEG monitoring indication (acute neonatal encephalopathy [ANE], suspicious clinical events [SCEs], or other high-risk conditions [OHRs]), age, medication status, and early EEG abnormalities (including the presence of epileptiform discharges and abnormal background continuity, amplitude, asymmetry, asynchrony, excessive sharp transients, and burst suppression) on time to first seizure and overall seizure risk using Kaplan-Meier survival curves and multivariable Cox proportional hazards models.ResultsSeizures occurred in 28% of high-risk neonates. Discontinuation of monitoring after 24 hours of seizure-freedom would have missed 8.5% of neonates with seizures. Overall seizure risk was lower in neonates monitored for ANE compared to OHR (P = .004) and trended lower compared to SCE (P = .097). The time course of seizure presentation varied by group, where the probability of future seizure was less than 1% after 17 hours of seizure-free monitoring in the SCE group, but required 42 hours in the OHR group, and 73 hours in the ANE group. The presence of early epileptiform discharges increased seizure risk in each group (ANE: adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.23-15.13, P = .022; SCE: aHR 10.95, 95% CI 4.77-25.14, P < 1e-07; OHR: aHR 56.90, 95% CI 10.32-313.72, P < 1e-05).SignificanceNeonates who undergo cEEG are at high risk for seizures, and risk varies by monitoring indication and early EEG findings. Seizures are captured in nearly all neonates undergoing monitoring for SCE within 24 hours of cEEG monitoring. Neonates monitored for OHR and ANE can present with delayed seizures and require longer durations of monitoring. Early epileptiform discharges are the best early EEG feature to predict seizure risk.
| S-EPMC7083278 | biostudies-literature
Project description:BackgroundAn ancillary study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia examined the hypothesis that neonates randomized to receive erythropoietin (Epo) would have a lower seizure risk and burden compared with neonates who received placebo.MethodsElectroencephalograms (EEGs) from 7/17 HEAL trial centers were reviewed. Seizure presence was compared across treatment groups using a logistic regression model adjusting for treatment, HIE severity, center, and seizure burden prior to the first dose. Among neonates with seizures, differences across treatment groups in median maximal hourly seizure burden were assessed using adjusted quantile regression models.ResultsForty-six of 150 (31%) neonates had EEG seizures (31% in Epo vs 30% in placebo, p = 0.96). Maximal hourly seizure burden after the study drug was not significantly different between groups (median 11.4 for Epo, IQR: 5.6, 18.1 vs median 9.7, IQR: 4.9, 21.0 min/h for placebo).ConclusionIn neonates with HIE treated with hypothermia who were randomized to Epo or placebo, we found no meaningful between-group difference in seizure risk or burden. These findings are consistent with overall trial results, which do not support Epo use for neonates with HIE undergoing therapeutic hypothermia.ImpactIn the HEAL trial of erythropoietin (Epo) vs placebo for neonates with encephalopathy presumed due to hypoxic-ischemic encephalopathy (HIE) who were also treated with therapeutic hypothermia, electrographic seizures were detected in 31%, which is lower than most prior studies. Epo did not reduce the proportion of neonates with acute provoked seizures (31% in Epo vs 30% in placebo) or maximal hourly seizure burden after the study drug (median 11.4, IQR 5.6, 18.1 for Epo vs median 9.7, IQR 4.9, 21.0 min/h for placebo). There was no anti- or pro-convulsant effect of Epo when combined with therapeutic hypothermia for HIE.
| S-EPMC10239788 | biostudies-literature
Project description:Objective A recent multicenter prospective study (DECIDE trial) examined the use of Ceribell Rapid Response EEG (Rapid-EEG) in the emergent evaluation and management of critically ill patients suspected to have non-convulsive seizures. We present a detailed, patient-level examination of seizures detected either on initial Rapid-EEG or subsequent conventional EEG within 24 h to investigate whether seizures were missed on Rapid-EEG due to the exclusion of midline/parasagittal coverage. Methods We identified from 164 patients studied in the DECIDE trial those who had seizures detected on Rapid-EEG but not conventional EEG (n = 6), conventional EEG but not Rapid-EEG (n = 4), or both Rapid-EEG and conventional EEG (n = 9). We examined the electrographic characteristics of ictal and interictal findings on both devices, especially their detection in lateral or midline/parasagittal chains, and patient clinical histories to identify contributors toward discordant seizure detection. Results Seizures detected on both EEG systems had similar electrographic appearance and laterality. Seizures detected only on conventional EEG (within 24 h following Rapid-EEG) were visible in the temporal chains, and external clinical factors (e.g., treatment with anti-seizure medications, sedation, and duration of recordings) explained the delayed presentation of seizures. Patients with seizures detected only by Rapid-EEG were treated with anti-seizure medications, and subsequent conventional EEG detected interictal highly epileptiform patterns with similar laterality. Conclusions Our case series demonstrates that electrographic data obtained from initial Rapid-EEG and subsequent conventional EEG monitoring are largely concordant relative to morphology and laterality. These findings are valuable to inform future investigation of abbreviated EEG systems to optimize management of suspected non-convulsive seizures and status epilepticus. Future, larger studies could further investigate the value of Rapid-EEG findings for forecasting and predicting seizures in long-term EEG recordings.
| S-EPMC9277057 | biostudies-literature
Project description:ImportanceNeonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently experience seizures, which are associated with adverse outcomes. Efforts to rapidly identify seizures and reduce seizure burden may positively change neurologic and neurodevelopmental outcomes.ObjectiveTo describe the onset, treatment, and evolution of seizures in a large cohort of newborns with HIE during TH assisted by a telehealth model and remote neuromonitoring approach.Design, setting, and participantsThis was a prospective, observational, multicenter cohort study performed between July 2017 and December 2021 in 32 hospitals in Brazil. Participants were newborns with HIE meeting eligibility criteria and receiving TH. Data were analyzed from November 2022 to April 2023.ExposureInfants with HIE receiving TH were remotely monitored with 3-channel amplitude-integrated electroencephalography (aEEG) including raw tracing and video imaging, and bedside clinicians received assistance from trained neonatologists and neurologists.Main outcomes and measuresData on modified Sarnat examination, presence, timing and seizure type, aEEG background activity, sleep-wake cycling, and antiepileptic drugs used were collected. Descriptive statistical analysis was used with independent t test, χ2, Mann-Whitney test, and post hoc analyses applied for associations.ResultsA total of 872 cooled newborns were enrolled; the median (IQR) gestational age was 39 (38-40) weeks, 518 (59.4%) were male, and 59 (6.8%) were classified as having mild encephalopathy by modified Sarnat examination, 504 (57.8%) as moderate, and 180 (20.6%) as severe. Electrographic seizures were identified in 296 newborns (33.9%), being only electrographic in 213 (71.9%) and clinical followed by electroclinical uncoupling in 50 (16.9%). Early abnormal background activity had a significant association with seizures. Infants with flat trace had the highest rate of seizures (58 infants [68.2%]) and the greatest association with the incidence of seizures (odds ratio [OR], 12.90; 95% CI, 7.57-22.22) compared with continuous normal voltage. The absence of sleep-wake cycling was also associated with a higher occurrence of seizures (OR, 2.22; 95% CI, 1.67-2.96). Seizure onset was most frequent between 6 and 24 hours of life (181 infants [61.1%]); however, seizure occurred in 34 infants (11.5%) during rewarming. A single antiepileptic drug controlled seizures in 192 infants (64.9%). The first line antiepileptic drug was phenobarbital in 294 (99.3%).Conclusions and relevanceIn this cohort study of newborns with HIE treated with TH, electrographic seizure activity occurred in 296 infants (33.9%) and was predominantly electrographic. Seizure control was obtained with a single antiepileptic drug in 192 infants (64.9%). These findings suggest neonatal neurocritical care can be delivered at remote limited resource hospitals due to innovations in technology and telehealth.
| S-EPMC10652158 | biostudies-literature
Project description:ObjectiveMorphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.Study designTerm and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008-2010 (SHIVER) and 2010-2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.Results244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C- 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C- 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia.ConclusionsClearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.Trial registrationwww.trialregister.nl NTR2529.
| S-EPMC6375702 | biostudies-literature
Project description:BackgroundInadvertent intraoperative hypothermia is frequent during open surgeries; however, few studies on hypothermia during laparoscopic abdominal surgery have been reported. We aimed to investigate the incidence and risk factors for hypothermia in patients undergoing laparoscopic abdominal surgery.MethodsThis single-center prospective cohort observational study involved patients undergoing laparoscopic surgery between October 2018 and June 2019. Data on core body temperature and potential variables were collected. A multivariate logistic regression analysis was performed to identify the risk factors associated with hypothermia. A Cox regression analysis was used to verify the sensitivity of the results.ResultsIn total, 690 patients were included in the analysis, of whom 200 (29.0%, 95% CI: 26%-32%) had a core temperature < 36°C. The core temperature decreased over time, and the incident hypothermia increased gradually. In the multivariate logistic regression analysis, age (OR = 1.017, 95% CI: 1.000-1.034, P = 0.050), BMI (OR = 0.938, 95% CI: 0.880-1.000; P = 0.049), baseline body temperature (OR = 0.025, 95% CI: 0.010-0.060; P < 0.001), volume of irrigation fluids (OR = 1.001, 95% CI: 1.000-1.001, P = 0.001), volume of urine (OR = 1.001, 95% CI: 1.000-1.003, P = 0.070), and duration of surgery (OR = 1.010, 95% CI: 1.006-1.015, P < 0.001) were significantly associated with hypothermia. In the Cox analysis, variables in the final model were age, BMI, baseline body temperature, volume of irrigation fluids, blood loss, and duration of surgery.ConclusionsInadvertent intraoperative hypothermia is evident in patients undergoing laparoscopic surgeries. Age, BMI, baseline body temperature, volume of irrigation fluids, and duration of surgery are significantly associated with intraoperative hypothermia.
| S-EPMC8460038 | biostudies-literature