Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (S v O 2 ) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO 2 in physiologic units. In addition, microvascular tissue oxygenation (StO 2 ) and indices of microvascular CBF (BFI) and CMRO 2 (CMRO 2i ) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO 2 were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O 2 /minute per 100 g, respectively. These CBF and CMRO 2 values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Keywords: cerebral blood flow; cerebral hemodynamics; diffuse optics; MRI; near-infrared spectroscopy; neonatal ischemia INTRODUCTION Congenital heart disease (CHD) affects B35,000 neonates each year in the United States. These patients suffer both short-and long-term neurologic sequelae. Periventricular leukomalacia is the most common cerebral injury found in this population. This type of injury is characterized by focal necrosis in the periventricular white matter, and it is associated with pyknotic glial nuclei and reactive gliosis. 1,2 During the early stages of brain development, the oligodendrocyte (brain glial cells) precursors are metabolically very active and highly susceptible to injury from reduced blood flow and oxygen delivery. Hence, hypoxiaischemia has been implicated as a major cause of this injury in CHD neonates.Periventricular leukomalacia leads to impaired myelination and has been linked to worse neurodevelopmental outcomes in premature infants and postulated to cause (at least in part) the impaired cognition and cerebral palsy commonly seen in this cohort of infants with CHD. 3,4 Quantification of the hemodynamic and metabolic state of these neonates via measurements of cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen consumption (CMRO 2 ) should provide valuable information toward understanding the interaction between cardiac pathophysiology and subsequent cerebral health. Potentially, such new knowledge could help predict and prevent adverse outcomes.

Objective Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately half of the HLHS survivors exhibit neurobehavioral symptoms believed to be associated with this injury, though the exact timing of the injury is not known. Methods Neonates with HLHS were recruited for pre- and post-operative monitoring of cerebral oxygen saturation (ScO2), cerebral oxygen extraction fraction (OEF), and cerebral blood flow (CBF) using two non-invasive optical-based techniques, namely diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomical magnetic resonance imaging (MRI) scans were performed prior to and approximately one week after surgery in order to quantify the extent and timing of the acquired white matter injury. Risk factors for developing new or worsened white matter injury were assessed using uni- and multi-variate logistic regression. Results Thirty-seven neonates with HLHS were studied. In a univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time-to-surgery (p=0.0003). In a multivariate model, longer time between birth and surgery (i.e., time-to-surgery), delayed sternal closure, and higher pre-operative CBF were predictors of post-operative white matter injury. Additionally, longer time-to-surgery and higher pre-operative CBF on morning of surgery were correlated with lower ScO2 (p=0.03 and p=0.05) and higher OEF (p=0.05 and p=0.05). Conclusions Longer time-to-surgery is associated with new post-operative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation may decrease the likelihood of acquiring postoperative white matter injury.

IMPORTANCE There are few data on the prevalence or outcome of bystander cardiopulmonary resuscitation (BCPR) in children 18 years and younger. OBJECTIVE To characterize BCPR in pediatric out-of-hospital cardiac arrests (OHCAs). DESIGN, SETTING, AND PARTICIPANTS This analysis of the Cardiac Arrest Registry to Enhance Survival database investigated nontraumatic OHCAs in children 18 years and younger from January 2013 through December 2015.EXPOSURES Bystander CPR, which included conventional CPR and compression-only CPR. MAIN OUTCOMES AND MEASURESOverall survival and neurologically favorable survival, defined as a Cerebral Performance Category score of 1 or 2, at the time of hospital discharge. RESULTSOf the 3900 children younger than 18 years with OHCA, 2317 (59.4%) were infants, 2346 (60.2%) were female, and 3595 (92.2%) had nonshockable rhythms. Bystander CPR was performed on 1814 children (46.5%) and was more common for white children (687 of 1221 [56.3%]) compared with African American children (447 of 1134 [39.4%]) and Hispanic children (197 of 455 [43.3%]) (P < .001). Overall survival and neurologically favorable survival were 11.3% (440 of 3900) and 9.1% (354 of 3900), respectively. On multivariable analysis, BCPR was independently associated with improved overall survival (adjusted proportion,

Aim Adequate coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) is essential for establishing return of spontaneous circulation. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of asphyxia-associated cardiac arrest. We hypothesized that a hemodynamic directed approach would improve short-term survival compared to depth-guided care. Methods After 7 minutes of asphyxia, followed by induction of ventricular fibrillation, 19 female 3-month old swine (31 ± 0.4 kg) were randomized to receive one of three resuscitation strategies: 1) Hemodynamic Directed Care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain CPP > 20 mmHg; 2) Depth 33mm (D33): target CC depth of 33mm with standard American Heart Association (AHA) epinephrine dosing; or 3) Depth 51mm (D51): target CC depth of 51mm with standard AHA epinephrine dosing. All animals received manual CPR guided by audiovisual feedback for 10 minutes before first shock. Results 45-minute survival was higher in the CPP-20 group (6/6) compared to D33 (1/7) or D51 (1/6) groups; p=0.002. Coronary perfusion pressures were higher in the CPP-20 group compared to D33 (p=0.011) and D51 (p=0.04), and in survivors compared to non-survivors (p<0.01). Total number of vasopressor doses administered and defibrillation attempts were not different. Conclusions Hemodynamic directed care targeting CPPs > 20 mmHg improves short-term survival in an intensive care unit porcine model of asphyxia-associated cardiac arrest.

We evaluated the relationship between clinical features and hypoxic-ischemic injury (HII) shown by diffusion-weighted MRI (DWI) in young children with head trauma, comparing inflicted trauma (IT) to accidental trauma (AT). This single-center consecutive cohort study included children age birth to 36 months admitted for head injury July 2001 to December 2004 with brain magnetic resonance imaging (MRI) obtained < or =1 week, identified from prospectively maintained registries of children with trauma. Clinical and radiological data during the hospital stay were extracted from medical records. MRIs were analyzed by study examiners blinded to clinical status and scored by type, severity and location of lesions attributable to traumatic, hypoxic-ischemic, or mixed injury patterns. 30 IT patients and 22 AT patients met inclusion criteria. IT cases were younger than AT, 3.0 versus 8.5 months. Mean time to MRI in IT (2.1 days) was similar to AT (1.9 days). HII was more common in IT (11 of 30) than AT (2/22, p = 0.03). Children with HII more commonly had seizures, needed intubation at presentation, and needed neurosurgical intervention compared to those without HII. Most patients with HII (10/14) required in-patient rehabilitation compared to those without HII (4/38). Our study is the first to characterize HII using diffusion-weighted MRI in young children, comparing IT and AT. The higher rate of HII on DWI-MRI in IT than in AT is likely multifactorial, involving respiratory insufficiency, seizures, and intracranial mass-occupying lesions requiring neurosurgical intervention. HII predicted need for in-patient rehabilitation in a large majority of children.

Objectives The American Clinical Neurophysiology Society recommends continuous electroencephalographic monitoring after neonatal cardiac surgery because seizures are common, often subclinical, and associated with worse neurocognitive outcomes. We performed a quality improvement project to monitor for postoperative seizures in neonates with congenital heart disease after surgery with cardiopulmonary bypass. Methods We implemented routine continuous electroencephalographic monitoring and reviewed the results for an 18-month period. Clinical data were collected by chart review, and continuous electroencephalographic tracings were interpreted using standardized American Clinical Neurophysiology Society terminology. Electrographic seizures were classified as electroencephalogram-only or electroclinical seizures. Multiple logistic regression was used to assess associations between seizures and potential clinical and electroencephalogram predictors. Results A total of 161 of 172 eligible neonates (94%) underwent continuous electroencephalographic monitoring. Electrographic seizures occurred in 13 neonates (8%) beginning at a median of 20 hours after return to the intensive care unit after surgery. Neonates with all types of congenital heart disease had seizures. Seizures were electroencephalogram only in 11 neonates (85%). Status epilepticus occurred in 8 neonates (62%). In separate multivariate models, delayed sternal closure or longer deep hypothermic circulatory arrest duration was associated with an increased risk for seizures. Mortality was higher among neonates with than without seizures (38% vs 3%, P<.001). Conclusions Continuous electroencephalographic monitoring identified seizures in 8%of neonates after cardiac surgery with cardiopulmonary bypass. The majority of seizures had no clinical correlate and would not have been otherwise identified. Seizure occurrence is a marker of greater illness severity and increased mortality. Further study is needed to determinewhether seizure identification and management lead to improved outcomes.

Objective We aimed to determine the incidence and risk factors for electrographic seizures (ES) in neonates and children requiring extracorporeal membrane oxygenation (ECMO) support. Design Prospective quality improvement project. Setting Quaternary care pediatric institution. Patients Consistent with American Clinical Neurophysiology Society EEG monitoring recommendations, neonates and children requiring ECMO support underwent clinically indicated EEG monitoring. Interventions We performed a two-year quality improvement study from July 2013 – June 2015 evaluating ES incidence and risk factors. Main Results 99 of 112 patients (88%) requiring ECMO support underwent EEG monitoring. ES occurred in 18 patients (18%), of which 11 patients (61%) had electrographic status epilepticus and 15 patients (83%) had exclusively EEG-only seizures. ES were more common in patients with low cardiac output syndrome (p=0.03). Patients with ES were more likely to die prior to discharge (72% vs 30%, p=0.01) and have unfavorable outcomes (54% vs 17%, p=0.004) than those without ES. Conclusions ES occurred in 18% of neonates and children requiring ECMO support, often constituted electrographic status epilepticus, and were often EEG-only thereby requiring EEG monitoring for identification. Low cardiac output syndrome was associated with an increased risk for ES. ES were associated with higher mortality and unfavorable outcomes. Further investigation is needed to determine whether ES identification and management improves outcomes.

In the United States of America, approximately 40,000 infants are born annually with congenitally malformed hearts. Children with defects that require complex surgical palliation, or definitive repair, face many challenges in achieving optimal short-term and long-term growth. The presence of associated chromosomal abnormalities, cyanosis, and cardiac failure adds to the complexity and challenge. In this review, we address three themes related to feeding, growth, and nutrition of infants after neonatal cardiac surgery: nutritional challenges after chylothorax; breastfeeding after surgery; and the challenges of feeding after discharge. Chylothorax is a rare complication following cardiothoracic surgery in children. Children with chylothorax have nutritional depletion secondary to protein losses in chylous fluid, hypovolaemia, and electrolyte losses. In spite of the evidence supporting the use of human milk and breastfeeding in preterm infants, barriers to its use appear to persist in infants with critical cardiac disease. Yet, human milk is the preferred form of nutrition for well, preterm, or ill infants. It is well documented that after complex neonatal cardiac surgery medical teams and families struggle with infant feeding problems. Parents have described feeding their children as difficult, time consuming, and anxiety producing. Medical complications such as chylothorax, limited access to human milk, and parental concerns and stress about feeding are but three of the myriad of factors that may contribute to poor outcomes regarding nutrition and growth. Compelling evidence exists that this multi-factorial problem must be addressed with both physiological and behavioural strategies.