Predictors of the inability to achieve full oral feeding in postoperative infants with CHD.

OBJECTIVES: Poor oral feeding is a known contributor to growth challenges in neonates with complex CHD who require early surgery. Almost 60% of these infants do not achieve full oral feeding by hospital discharge. This study's objective was to identify predictors of the inability to achieve full oral feeding by discharge in neonates with complex CHD following surgical intervention with cardiopulmonary bypass. STUDY DESIGN: A retrospective analysis of a prospective study of 192 full-term neonates with complex CHD was performed. A stepwise selection logistic regression model was developed to predict oral feeding status at hospital discharge. Univariate subgroup analysis was performed with groups determined based on a CHD classification system. RESULTS: 58% of neonates (112/192) failed to achieve full oral feeding by hospital discharge. A logistic regression model identified duration of deep hypothermic circulatory arrest and reintubation as predictors of the inability to achieve full oral feeding. Among neonates who achieved full oral feeding by discharge (42%), only 7.5% did so after postoperative day 10. Brain maturation, brain injury, and preoperative oral feeding were not predictors of full postoperative oral feeding. CONCLUSIONS: Many infants with CHD fail to achieve full oral feeding by time of hospital discharge. Longer duration of deep hypothermic circulatory arrest and increased number of intubations were predictive of poor feeding after surgery. Prolonging hospitalisation solely to achieve full oral feeding after postoperative day ten is of limited utility; earlier discharge should be promoted to avoid negative impacts on neonatal neurodevelopment as unintended consequences of lengthy hospitalisations.

A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus.

BACKGROUND: Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE. METHODS: Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021. RESULTS: We identified 117 study participants (28 neonates), including 79 (68%) who received midazolam and 38 (32%) who received ketamine as the first-line anesthetic infusions. Seizures terminated more often in study participants administered ketamine (61%, 23/38) than midazolam (28%, 22/79; odds ratio [OR] 3.97, 95% confidence interval [CI] 1.76-8.98; P < 0.01). Adverse effects occurred more often in study participants administered midazolam (24%, 20/79) than ketamine (3%, 1/38; OR 12.54, 95% CI 1.61-97.43; P = 0.016). Study participants administered ketamine were younger, ketamine was used more often for children with acute symptomatic seizures, and midazolam was used more often for children with epilepsy. Multivariable logistic regression of seizure termination by first-line anesthetic infusion (ketamine or midazolam) including age at SE onset, SE etiology category, and individual seizure duration at anesthetic infusion initiation indicated seizures were more likely to terminate following ketamine than midazolam (OR 4.00, 95% CI 1.69-9.49; P = 0.002) and adverse effects were more likely following midazolam than ketamine (OR 13.41, 95% CI 1.61-111.04; P = 0.016). Survival to discharge was higher among study participants who received midazolam (82%, 65/79) than ketamine (55%, 21/38; P = 0.002), although treating clinicians did not attribute any deaths to ketamine or midazolam. CONCLUSIONS: Among children and neonates with RSE, ketamine was more often followed by seizure termination and less often associated with adverse effects than midazolam when administered as the first-line anesthetic infusion. Further prospective data are needed to compare first-line anesthetics for RSE.

Oral feeding dysfunction in post-operative infants with CHDs: a scoping review.

Post-operative oral feeding difficulties in neonates and infants with CHD is common. While pre-operative oral feeding may be normal, oral feeding challenges manifest in the post-operative period without a clearly defined aetiology. The objective of this scoping review was to examine post-operative oral feeding in full-term neonates and infants with a CHD. Electronic databases query (1 January 1975-31 May 2021), hand-search of the reference lists of included studies, contact with experts, and review of relevant conferences were performed to identify quantitative studies evaluating post-operative oral feeding in full-term neonates and infants with a CHD. Associations with additional quantitative variables in these studies were also examined. Twenty-five studies met inclusion criteria. Eighty per cent were cohort studies that utilised retrospective chart review from a single institution. The primary variable of interest in all studies was oral feeding status upon discharge from neonatal hospitalisation. The most common risk factors evaluated with poor feeding at time of discharge were birth weight (36% of included studies), gestational age (44%), duration of post-operative intubation (48%), cardiac diagnosis (40%), and presence of genetic syndrome or chromosomal anomaly (36%). The most common health-related outcomes evaluated were length of hospital stay (40%) and length of ICU stay (16%). Only the health-related outcomes of length of hospital stay and length of ICU stay were consistently significantly associated with poor post-operative oral feeding across studies in this review. A clear aetiology of poor post-operative oral feeding remains unknown.

Neurologic complications of infective endocarditis in children.

OBJECTIVES: To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications. STUDY DESIGN: Retrospective cohort study of children aged 0-18 years hospitalised at a tertiary children's hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis. RESULTS: Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications. CONCLUSIONS: Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.

Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report.

BACKGROUND: Electroconvulsive therapy is used to treat depression and schizophrenia with infrequent use in pediatric patients. We report a case of an adolescent with autism spectrum disorder and acute catatonia that presented with status epilepticus (SE) and prolonged neurologic deficits with unilateral left cerebral edema on imaging following unilateral electroconvulsive therapy (ECT) on the right side, subsequently found to have a CACNA1a pathogenic variant. This case highlights a potential adverse effect of ECT in patients with CACNA1a related disorders. CASE: The patient received unilateral ECT to the right side and subsequently had an episode of SE with right-sided hemiplegia for 72 h prior to regaining some function with persistent mild right-hand weakness that persisted for at least 1-2 weeks. A brain MRI 2 days after ECT was unremarkable, but a repeat MRI on day four of admission showed left hemisphere cortical diffusion restriction, increased perfusion and T2 prolongation suggestive of cortical edema. They had whole exome genetic testing sent after discharge that showed a known pathogenic CACNA1a variant (p.I1709T). CACNA1a encodes the P/Q type calcium channels and deleterious variants in this gene result in a channelopathy associated with a spectrum of neurodevelopmental disorders that include autism spectrum disorder, hemiplegic migraine with unilateral cerebral edema, epileptic encephalopathies, or episodic ataxia syndromes. CONCLUSION: A literature review of ECT and neurologic deficits showed that most neurologic deficits resolve within 30 min of ECT. Case reports of prolonged deficits are rare and there are no prior reports of acute MRI changes related to ECT. Thus, the acute deterioration and MRI findings in this patient are likely related to the underlying CACNA1a channelopathy disorder with ECT as a precipitating event. This case report suggests care should be taken when using ECT in patients with pathogenic variants in CACNA1a. Furthermore, it reinforces the utility and importance of expanded genetic testing in patients with neurodevelopmental disorders as findings can provide valuable information that can guide treatment decisions.

Periodic and rhythmic patterns in critically ill children: Incidence, interrater agreement, and seizures.

OBJECTIVES: We aimed to determine the incidence of periodic and rhythmic patterns (PRP), assess the interrater agreement between electroencephalographers scoring PRP using standardized terminology, and analyze associations between PRP and electrographic seizures (ES) in critically ill children. METHODS: This was a prospective observational study of consecutive critically ill children undergoing continuous electroencephalographic monitoring (CEEG). PRP were identified by one electroencephalographer, and then two pediatric electroencephalographers independently scored the first 1-h epoch that contained PRP using standardized terminology. We determined the incidence of PRPs, evaluated interrater agreement between electroencephalographers scoring PRP, and evaluated associations between PRP and ES. RESULTS: One thousand three hundred ninety-nine patients underwent CEEG. ES occurred in 345 (25%) subjects. PRP, ES + PRP, and ictal-interictal continuum (IIC) patterns occurred in 142 (10%), 81 (6%), and 93 (7%) subjects, respectively. The most common PRP were generalized periodic discharges (GPD; 43, 30%), lateralized periodic discharges (LPD; 34, 24%), generalized rhythmic delta activity (GRDA; 34, 24%), bilateral independent periodic discharges (BIPD; 14, 10%), and lateralized rhythmic delta activity (LRDA; 11, 8%). ES risk varied by PRP type (p < .01). ES occurrence was associated with GPD (odds ratio [OR] = 6.35, p < .01), LPD (OR = 10.45, p < .01), BIPD (OR = 6.77, p < .01), and LRDA (OR = 6.58, p < .01). Some modifying features increased the risk of ES for each of those PRP. GRDA was not significantly associated with ES (OR = 1.34, p = .44). Each of the IIC patterns was associated with ES (OR = 6.83-8.81, p < .01). ES and PRP occurred within 6 h (before or after) in 45 (56%) subjects. SIGNIFICANCE: PRP occurred in 10% of critically ill children who underwent CEEG. The most common patterns were GPD, LPD, GRDA, BIPD, and LRDA. The GPD, LPD, BIPD, LRDA, and IIC patterns were associated with ES. GRDA was not associated with ES.

Validation of a model to predict electroencephalographic seizures in critically ill children.

OBJECTIVE: Electroencephalographic seizures (ESs) are common in encephalopathic critically ill children, but identification requires extensive resources for continuous electroencephalographic monitoring (CEEG). In a previous study, we developed a clinical prediction rule using three clinical variables (age, acute encephalopathy category, clinically evident seizure[s] prior to CEEG initiation) and two electroencephalographic (EEG) variables (EEG background category and interictal discharges within the first 30 minutes of EEG) to identify patients at high risk for ESs for whom CEEG might be essential. In the current study, we aimed to validate the ES prediction model using an independent cohort. METHODS: The prospectively acquired validation cohort consisted of 314 consecutive critically ill children treated in the Pediatric Intensive Care Unit of a quaternary care referral hospital with acute encephalopathy undergoing clinically indicated CEEG. We calculated test characteristics using the previously developed prediction model in the validation cohort. As in the generation cohort study, we selected a 0.10 cutpoint to emphasize sensitivity. RESULTS: The incidence of ESs in the validation cohort was 22%. The generation and validation cohorts were alike in most clinical and EEG characteristics. The ES prediction model was well calibrated and well discriminating in the validation cohort. The model had a sensitivity of 90%, specificity of 37%, positive predictive value of 28%, and negative predictive value of 93%. If applied, the model would limit 31% of patients from undergoing CEEG while failing to identify 10% of patients with ESs. The model had similar performance characteristics in the generation and validation cohorts. SIGNIFICANCE: A model employing five readily available clinical and EEG variables performed well when validated in a new consecutive cohort. Implementation would substantially reduce CEEG utilization, although some patients with ESs would not be identified. This model may serve a critical role in targeting limited CEEG resources to critically ill children at highest risk for ESs.

Development of a model to predict electroencephalographic seizures in critically ill children.

OBJECTIVE: Electroencephalographic seizures (ESs) are common in encephalopathic critically ill children, but ES identification with continuous electroencephalography (EEG) monitoring (CEEG) is resource-intense. We aimed to develop an ES prediction model that would enable clinicians to stratify patients by ES risk and optimally target limited CEEG resources. We aimed to determine whether incorporating data from a screening EEG yielded better performance characteristics than models using clinical variables alone. METHODS: We performed a prospective observational study of 719 consecutive critically ill children with acute encephalopathy undergoing CEEG in the pediatric intensive care unit of a quaternary care institution between April 2017 and February 2019. We identified clinical and EEG risk factors for ES. We evaluated model performance with area under the receiver-operating characteristic (ROC) curve (AUC), validated the optimal model with the highest AUC using a fivefold cross-validation, and calculated test characteristics emphasizing high sensitivity. We applied the optimal operating slope strategy to identify the optimal cutoff to define whether a patient should undergo CEEG. RESULTS: The incidence of ES was 26%. Variables associated with increased ES risk included age, acute encephalopathy category, clinical seizures prior to CEEG initiation, EEG background, and epileptiform discharges. Combining clinical and EEG variables yielded better model performance (AUC 0.80) than clinical variables alone (AUC 0.69; P < .01). At a 0.10 cutoff selected to emphasize sensitivity, the optimal model had a sensitivity of 92%, specificity of 37%, positive predictive value of 34%, and negative predictive value of 93%. If applied, the model would limit 29% of patients from undergoing CEEG while failing to identify 8% of patients with ES. SIGNIFICANCE: A model employing readily available clinical and EEG variables could target limited CEEG resources to critically ill children at highest risk for ES, making CEEG-guided management a more viable neuroprotective strategy.

Noninvasive optical measurement of microvascular cerebral hemodynamics and autoregulation in the neonatal ECMO patient.

BACKGROUND: Extra-corporeal membrane oxygenation (ECMO) is a life-saving intervention for severe respiratory and cardiac diseases. However, 50% of survivors have abnormal neurologic exams. Current ECMO management is guided by systemic metrics, which may poorly predict cerebral perfusion. Continuous optical monitoring of cerebral hemodynamics during ECMO holds potential to detect risk factors of brain injury such as impaired cerebrovascular autoregulation (CA). METHODS: We conducted daily measurements of microvascular cerebral blood flow (CBF), oxygen saturation, and total hemoglobin concentration using diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy in nine neonates. We characterize CA utilizing the correlation coefficient (DCSx) between CBF and mean arterial blood pressure (MAP) during ECMO pump flow changes. RESULTS: Average MAP and pump flow levels were weakly correlated with CBF and were not correlated with cerebral oxygen saturation. CA integrity varied between individuals and with time. Systemic measurements of MAP, pulse pressure, and left cardiac dysfunction were not predictive of impaired CA. CONCLUSIONS: Our pilot results suggest that systemic measures alone cannot distinguish impaired CA from intact CA during ECMO. Furthermore, optical neuromonitoring could help determine patient-specific ECMO pump flows for optimal CA integrity, thereby reducing risk of secondary brain injury. IMPACT: Cerebral blood flow and oxygenation are not well predicted by systemic proxies such as ECMO pump flow or blood pressure. Continuous, quantitative, bedside monitoring of cerebral blood flow and oxygenation with optical tools enables new insight into the adequacy of cerebral perfusion during ECMO. A demonstration of hybrid diffuse optical and correlation spectroscopies to continuously measure cerebral blood oxygen saturation and flow in patients on ECMO, enabling assessment of cerebral autoregulation. An observation of poor correlation of cerebral blood flow and oxygenation with systemic mean arterial pressure and ECMO pump flow, suggesting that clinical decision making guided by target values for these surrogates may not be neuroprotective. ~50% of ECMO survivors have long-term neurological deficiencies; continuous monitoring of brain health throughout therapy may reduce these tragically common sequelae through brain-focused adjustment of ECMO parameters.

Electroencephalographic seizures in critically ill children: Management and adverse events.

OBJECTIVE: Guidelines recommend that encephalopathic critically ill children undergo continuous electroencephalographic (CEEG) monitoring for electrographic seizure (ES) identification and management. However, limited data exist on antiseizure medication (ASM) safety for ES treatment in critically ill children. METHODS: We performed a single-center prospective observational study of encephalopathic critically ill children undergoing CEEG. Clinical and EEG features and ASM utilization patterns were evaluated. We determined the incidence, types, and risk factors for adverse events associated with ASM administration. RESULTS: A total of 472 consecutive critically ill children undergoing CEEG were enrolled. ES occurred in 131 children (28%). Clinicians administered ASM to 108 children with ES (82%). ES terminated after the initial ASM in 38% of patients who received one ASM, after the second ASM in 35% of patients who received two ASMs, after the third ASM in 50% of patients who received three ASMs, and after the fourth ASM in 53% of patients who received four ASMs. Thirty patients (28%) received anesthetic infusions for ES management. Adverse events occurred in 18 patients (17%). Adverse effects were expected and resolved in all patients, and they were generally serious (in 15 patients) and definitely related (in 12 patients). Adverse events were rare in patients with acute symptomatic seizures requiring only one to two ASMs for treatment, but were more common in children with epilepsy, ictal-interictal continuum EEG patterns, or patients requiring more extensive ASM management. SIGNIFICANCE: ES ceased after one ASM in only 38% of critically ill children but ceased after two ASMs in 73% of critically ill children. Thus, ES management was often accomplished with readily available medications, but optimization of multistep ES management strategies might be beneficial. Adverse events were rare and manageable in children with acute symptomatic seizures requiring only one to two ASMs for treatment. Future studies are needed to determine whether management of acute symptomatic ES improves neurobehavioral outcomes.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.

Validation of a Model for Targeted EEG Monitoring Duration in Critically Ill Children.

PURPOSE: Continuous EEG monitoring (CEEG) to identify electrographic seizures (ES) in critically ill children is resource intense. Targeted strategies could enhance implementation feasibility. We aimed to validate previously published findings regarding the optimal CEEG duration to identify ES in critically ill children. METHODS: This was a prospective observational study of 1,399 consecutive critically ill children with encephalopathy. We validated the findings of a multistate survival model generated in a published cohort ( N = 719) in a new validation cohort ( N = 680). The model aimed to determine the CEEG duration at which there was <15%, <10%, <5%, or <2% risk of experiencing ES if CEEG were continued longer. The model included baseline clinical risk factors and emergent EEG risk factors. RESULTS: A model aiming to determine the CEEG duration at which a patient had <10% risk of ES if CEEG were continued longer showed similar performance in the generation and validation cohorts. Patients without emergent EEG risk factors would undergo 7 hours of CEEG in both cohorts, whereas patients with emergent EEG risk factors would undergo 44 and 36 hours of CEEG in the generation and validation cohorts, respectively. The <10% risk of ES model would yield a 28% or 64% reduction in CEEG hours compared with guidelines recommending CEEG for 24 or 48 hours, respectively. CONCLUSIONS: This model enables implementation of a data-driven strategy that targets CEEG duration based on readily available clinical and EEG variables. This approach could identify most critically ill children experiencing ES while optimizing CEEG use.

EEG Monitoring in Critically Ill Children: Establishing High-Yield Subgroups.

PURPOSE: Continuous EEG monitoring (CEEG) is increasingly used to identify electrographic seizures (ES) in critically ill children, but it is resource intense. We aimed to assess how patient stratification by known ES risk factors would impact CEEG utilization. METHODS: This was a prospective observational study of critically ill children with encephalopathy who underwent CEEG. We calculated the average CEEG duration required to identify a patient with ES for the full cohort and subgroups stratified by known ES risk factors. RESULTS: ES occurred in 345 of 1,399 patients (25%). For the full cohort, an average of 90 hours of CEEG would be required to identify 90% of patients with ES. If subgroups of patients were stratified by age, clinically evident seizures before CEEG initiation, and early EEG risk factors, then 20 to 1,046 hours of CEEG would be required to identify a patient with ES. Patients with clinically evident seizures before CEEG initiation and EEG risk factors present in the initial hour of CEEG required only 20 (<1 year) or 22 (≥1 year) hours of CEEG to identify a patient with ES. Conversely, patients with no clinically evident seizures before CEEG initiation and no EEG risk factors in the initial hour of CEEG required 405 (<1 year) or 1,046 (≥1 year) hours of CEEG to identify a patient with ES. Patients with clinically evident seizures before CEEG initiation or EEG risk factors in the initial hour of CEEG required 29 to 120 hours of CEEG to identify a patient with ES. CONCLUSIONS: Stratifying patients by clinical and EEG risk factors could identify high- and low-yield subgroups for CEEG by considering ES incidence, the duration of CEEG required to identify ES, and subgroup size. This approach may be critical for optimizing CEEG resource allocation.

The use of novel diffuse optical spectroscopies for improved neuromonitoring during neonatal cardiac surgery requiring antegrade cerebral perfusion.

Background: Surgical procedures involving the aortic arch present unique challenges to maintaining cerebral perfusion, and optimal neuroprotective strategies to prevent neurological injury during such high-risk procedures are not completely understood. The use of antegrade cerebral perfusion (ACP) has gained favor as a neuroprotective strategy over deep hypothermic circulatory arrest (DHCA) due to the ability to selectively perfuse the brain. Despite this theoretical advantage over DHCA, there has not been conclusive evidence that ACP is superior to DHCA. One potential reason for this is the incomplete understanding of ideal ACP flow rates to prevent both ischemia from underflowing and hyperemia and cerebral edema from overflowing. Critically, there are no continuous, noninvasive measurements of cerebral blood flow (CBF) and cerebral oxygenation (StO2) to guide ACP flow rates and help develop standard clinical practices. The purpose of this study is to demonstrate the feasibility of using noninvasive, diffuse optical spectroscopy measurements of CBF and cerebral oxygenation during the conduct of ACP in human neonates undergoing the Norwood procedure. Methods: Four neonates prenatally diagnosed with hypoplastic left heart syndrome (HLHS) or a similar variant underwent the Norwood procedure with continuous intraoperative monitoring of CBF and cerebral oxygen saturation (StO2) using two non-invasive optical techniques, namely diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS). Changes in CBF and StO2 due to ACP were calculated by comparing these parameters during a stable 5 min period of ACP to the last 5 min of full-body CPB immediately prior to ACP initiation. Flow rates for ACP were left to the discretion of the surgeon and ranged from 30 to 50 ml/kg/min, and all subjects were cooled to 18°C prior to initiation of ACP. Results: During ACP, the continuous optical monitoring demonstrated a median (IQR) percent change in CBF of -43.4% (38.6) and a median (IQR) absolute change in StO2 of -3.6% (12.3) compared to a baseline period during full-body cardiopulmonary bypass (CPB). The four subjects demonstrated varying responses in StO2 due to ACP. ACP flow rates of 30 and 40 ml/kg/min (n = 3) were associated with decreased CBF during ACP compared to full-body CPB. Conversely, one subject with a higher flow6Di rate of 50 ml/kg/min demonstrated increased CBF and StO2 during ACP. Conclusions: This feasibility study demonstrates that novel diffuse optical technologies can be utilized for improved neuromonitoring in neonates undergoing cardiac surgery where ACP is utilized. Future studies are needed to correlate these findings with neurological outcomes to inform best practices during ACP in these high-risk neonates.

Periodic Discharges in Critically Ill Children: Predictors and Outcome.

OBJECTIVES: We aimed to identify clinical and EEG monitoring characteristics associated with generalized, lateralized, and bilateral-independent periodic discharges (GPDs, LPDs, and BIPDs) and to determine which patterns were associated with outcomes in critically ill children. METHODS: We performed a prospective observational study of consecutive critically ill children undergoing continuous EEG monitoring, including standardized scoring of GPDs, LPDs, and BIPDs. We identified variables associated with GPDs, LPDs, and BIPDs and assessed whether each pattern was associated with hospital discharge outcomes including the Glasgow Outcome Scale-Extended Pediatric version (GOS-E-Peds), Pediatric Cerebral Performance Category (PCPC), and mortality. RESULTS: PDs occurred in 7% (91/1,399) of subjects. Multivariable logistic regression indicated that patients with coma (odds ratio [OR], 3.45; 95% confidence interval [CI]: 1.55, 7.68) and abnormal EEG background category (OR, 6.85; 95% CI: 3.37, 13.94) were at increased risk for GPDs. GPDs were associated with mortality (OR, 3.34; 95% CI: 1.24, 9.02) but not unfavorable GOS-E-Peds (OR, 1.93; 95% CI: 0.88, 4.23) or PCPC (OR, 1.64; 95% CI: 0.75, 3.58). Patients with acute nonstructural encephalopathy did not experience LPDs, and LPDs were not associated with mortality or unfavorable outcomes. BIPDs were associated with mortality (OR, 3.68; 95% CI: 1.14, 11.92), unfavorable GOS-E-Peds (OR, 5.00; 95% CI: 1.39, 18.00), and unfavorable PCPC (OR, 5.96; 95% CI: 1.65, 21.46). SIGNIFICANCE: Patients with coma or more abnormal EEG background category had an increased risk for GPDs and BIPDs, and no patients with an acute nonstructural encephalopathy experienced LPDs. GPDs were associated with mortality and BIPDs were associated with mortality and unfavorable outcomes, but LPDs were not associated with unfavorable outcomes.

Cerebral microhemorrhages in children with congenital heart disease: Prevalence, risk factors, and impact on neurodevelopmental outcomes.

Background: Infants with complex congenital heart disease (CHD) require life-saving corrective/palliative heart surgery in the first weeks of life. These infants are at risk for brain injury and poor neurodevelopmental outcomes. Cerebral microhemorrhages (CMH) are frequently seen after neonatal bypass heart surgery, but it remains unknown if CMH are a benign finding or constitute injury. Herein, we investigate the risk factors for developing CMH and their clinical significance. Methods: 192 infants with CHD undergoing corrective cardiac surgery with cardiopulmonary bypass (CPB) at a single institution were prospectively evaluated with pre-(n = 183) and/or postoperative (n = 162) brain magnetic resonance imaging (MRI). CMH severity was scored based on total number of microhemorrhages. Antenatal, perioperative, and postoperative candidate risk factors for CMH and neurodevelopmental (ND) outcomes were analyzed. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley-III Scales of Infants and Toddler Development in a subset of patients (n = 82). Linear regression was used to analyze associations between risk factors or ND outcomes and presence/number of CMH. Results: The most common CHD subtypes were hypoplastic left heart syndrome (HLHS) (37%) and transposition of the great arteries (TGA) (33%). Forty-two infants (23%) had CMH present on MRI before surgery and 137 infants (85%) post-surgery. No parameters evaluated were significant risk factors for preoperative CMH. In multivariate analysis, cardiopulmonary bypass (CPB) duration (p < 0.0001), use of extracorporeal membrane oxygenation (ECMO) support (p < 0.0005), postoperative seizure(s) (p < 0.03), and lower birth weight (p < 0.03) were associated with new or worsened CMH postoperatively. Higher CMH number was associated with lower scores on motor (p < 0.03) testing at 18 months. Conclusion: CMH is a common imaging finding in infants with CHD with increased prevalence and severity after CPB and adverse impact on neurodevelopmental outcomes starting at a young age. Longer duration of CPB and need for postoperative ECMO were the most significant risk factors for developing CMH. However, presence of CMH on preoperative scans indicates non-surgical risk factors that are yet to be identified. Neuroprotective strategies to mitigate risk factors for CMH may improve neurodevelopmental outcomes in this vulnerable population.

Electroencephalography as a tool to predict cerebral oxygen metabolism during deep-hypothermic circulatory arrest in neonates with critical congenital heart disease.

Objectives: Recent research suggests that increased cerebral oxygen use during surgical intervention for neonates with congenital heart disease may play a role in the development of postoperative white matter injury. The objective of this study is to determine whether increased cerebral electrical activity correlates with greater decrease of cerebral oxygen saturation during deep hypothermic circulatory arrest. Methods: Neonates with critical congenital heart disease requiring surgical intervention during the first week of life were studied. All subjects had continuous neuromonitoring with electroencephalography and an optical probe (to quantify cerebral oxygen saturation) during cardiac surgical repair that involved the use of cardiopulmonary bypass and deep hypothermic circulatory arrest. A simple linear regression was used to investigate the association between electroencephalography metrics before the deep hypothermic circulatory arrest period and the change in cerebral oxygen saturation during the deep hypothermic circulatory arrest period. Results: Sixteen neonates had both neuromonitoring modalities attached during surgical repair. Cerebral oxygen saturation data from 5 subjects were excluded due to poor data quality, yielding a total sample of 11 neonates. A simple linear regression model found that the presence of electroencephalography activity at the end of cooling is positively associated with the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest (P < .05). Conclusions: Electroencephalography characteristics within 5 minutes before the initiation of deep hypothermic circulatory arrest may be useful in predicting the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest. Electroencephalography may be an important tool for guiding cooling and the initiation of circulatory arrest to potentially decrease the prevalence of new white matter injury in neonates with critical congenital heart disease.

Impaired Maternal-Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease.

Background Infants with congenital heart disease (CHD) are at risk for white matter injury (WMI) before neonatal heart surgery. Better knowledge of the causes of preoperative WMI may provide insights into interventions that improve neurodevelopmental outcomes in these patients. Methods and Results A prospective single-center study of preoperative WMI in neonates with CHD recorded data on primary cardiac diagnosis, maternal-fetal environment (MFE), delivery type, subject anthropometrics, and preoperative care. Total maturation score and WMI were assessed, and stepwise logistic regression modeling selected risk factors for WMI. Among subjects with severe CHD (n=183) who received a preoperative brain magnetic resonance imaging, WMI occurred in 40 (21.9%) patients. WMI prevalence (21.4%-22.1%) and mean volumes (119.7-160.4 mm3) were similar across CHD diagnoses. Stepwise logistic regression selected impaired MFE (odds ratio [OR], 2.85 [95% CI, 1.29-6.30]), male sex (OR, 2.27 [95% CI, 1.03-5.36]), and older age at surgery/magnetic resonance imaging (OR, 1.20 per day [95% CI, 1.03-1.41]) as risk factors for preoperative WMI and higher total maturation score values (OR, 0.65 per unit increase [95% CI, 0.43-0.95]) as protective. A quarter (24.6%; n=45) of subjects had ≥1 components of impaired MFE (gestational diabetes [n=12; 6.6%], gestational hypertension [n=11; 6.0%], preeclampsia [n=2; 1.1%], tobacco use [n=9; 4.9%], hypothyroidism [n=6; 3.3%], and other [n=16; 8.7%]). In a subset of 138 subjects, an exploratory analysis of additional MFE-related factors disclosed other potential risk factors for WMI. Conclusions This study is the first to identify impaired MFE as an important risk factor for preoperative WMI. Vulnerability to preoperative WMI was shared across CHD diagnoses.

Association of Ongoing Cerebral Oxygen Extraction During Deep Hypothermic Circulatory Arrest With Postoperative Brain Injury.

Cardiac surgery utilizing circulatory arrest is most commonly performed under deep hypothermia (∼18°C) to suppress tissue oxygen demand and provide neuroprotection during operative circulatory arrest. Studies investigating the effects of deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcomes of patients with congenital heart disease give conflicting results. Here, we address these issues by quantifying changes in cerebral oxygen saturation, blood flow, and oxygen metabolism in neonates during DHCA and investigating the association of these changes with postoperative brain injury. Neonates with critical congenital heart disease undergoing DHCA were recruited for continuous intraoperative monitoring of cerebral oxygen saturation (ScO2) and an index of cerebral blood flow (CBFi) using 2 noninvasive optical techniques, diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). Pre- and postoperative brain magnetic resonance imaging (MRI) was performed to detect white matter injury (WMI). Fifteen neonates were studied, and 11/15 underwent brain MRI. During DHCA, ScO2 decreased exponentially in time with a median decay rate of -0.04 min-1. This decay rate was highly variable between subjects. Subjects who had larger decreases in ScO2 during DHCA were more likely to have postoperative WMI (P = 0.02). Cerebral oxygen extraction persists during DHCA and varies widely from patient-to-patient. Patients with a higher degree of oxygen extraction during DHCA were more likely to show new WMI in postoperative MRI. These findings suggest cerebral oxygen extraction should be monitored during DHCA to identify patients at risk for hypoxic-ischemic injury, and that current commercial cerebral oximeters may underestimate cerebral oxygen extraction.