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.

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES: Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. METHODS: CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. RESULTS: Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). CONCLUSIONS: Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS.

What do epileptologists recommend about discontinuing antiepileptic drugs for a second time in children?

OBJECTIVE: There is a broad consensus that antiepileptic drugs (AEDs) may be withdrawn after two years of seizure freedom for most children with epilepsy. If seizures recur and are, again, completely controlled with AEDs, little is known about discontinuing a second time. We surveyed American and Canadian pediatric epileptologists to understand their current practice. METHODS: In 2014, a survey was sent via e-mail to 193 pediatric epileptologists to learn about AED discontinuation practices in children. The survey asked direct questions about practice and posed five "real-life" cases where the decision to discontinue might be difficult. Participants were identified through membership lists of several US and Canadian epilepsy organizations. RESULTS: There were 94 (49%) completed surveys. Sixty-three participants had ≥ 10 years in practice ("more experienced": mean 23 ± 9 years), and 31 had < 10 years ("less experienced": mean 6 ± 2 ). Overall, 62% recommended AED discontinuation for the first time after 2-3 years of seizure freedom, and 61% recommended discontinuation for the second time after 2-3 years. Fifty-six percent of "more experienced" clinicians required a longer seizure-free period prior to a second discontinuation (p < 0.001) compared with 26% of "less experienced" clinicians (p = ns). Overall, most participants suggested an AED taper duration of 2-6 months for the first and second attempts, 52% and 68%, respectively. Both groups wean AEDs more slowly during the second attempt (p < 0.001). There was only 40-60% agreement among participants to discontinue AEDs in four of the cases. CONCLUSION: Nearly half (46%) of pediatric epileptologists require a longer seizure-free period the second time they attempt to discontinue AEDs compared with the first attempt and wean down AEDs somewhat more slowly. Although a variety of factors influence decision-making, there was a high level of disagreement to discontinue AEDs a second time in "real-life" cases.

Scoring system for periventricular leukomalacia in infants with congenital heart disease.

BACKGROUND: Currently two magnetic resonance imaging (MRI) methods have been used to assess periventricular leukomalacia (PVL) severity in infants with congenital heart disease: manual volumetric lesion segmentation and an observational categorical scale. Volumetric classification is labor intensive and the categorical scale is quick but unreliable. We propose the quartered point system (QPS) as a novel, intuitive, time-efficient metric with high interrater agreement. METHODS: QPS is an observational scale that asks the rater to score MRIs on the basis of lesion size, number, and distribution. Pre- and postoperative brain MRIs were obtained on term congenital heart disease infants. Three independent observers scored PVL severity using all three methods: volumetric segmentation, categorical scale, and QPS. RESULTS: One-hundred and thirty-five MRIs were obtained from 72 infants; PVL was seen in 48 MRIs. Volumetric measurements among the three raters were highly concordant (ρc = 0.94-0.96). Categorical scale severity scores were in poor agreement between observers (κ = 0.17) and fair agreement with volumetrically determined severity (κ = 0.26). QPS scores were in very good agreement between observers (κ = 0.82) and with volumetric severity (κ = 0.81). CONCLUSION: QPS minimizes training and sophisticated radiologic analysis and increases interrater reliability. QPS offers greater sensitivity to stratify PVL severity and has the potential to more accurately correlate with neurodevelopmental outcomes.

Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome.

OBJECTIVE: Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown. METHODS: Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression. RESULTS: A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P=.0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P=.03 and P=.05, respectively) and greater oxygen extraction fraction (P=.05 for both). CONCLUSIONS: A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury.

Prevalence of and risk factors for acute occlusive arterial injury following pediatric cardiac catheterization: a large single-center cohort study.

OBJECTIVES: To describe the prevalence of and identify risk factors for acute occlusive arterial injury (AOAI) in a large volume pediatric cardiac catheterization laboratory. BACKGROUND: AOAI is a known complication after pediatric cardiac catheterization. Prevalence and risk factors in the modern era are incompletely described. METHODS: A retrospective cohort study including all cardiac catheterization procedures performed between January 1, 2005 and June 30, 2010 was performed. Case status was defined by ≥1 of the following: exam consistent with occlusive arterial injury, use of an anticoagulant within 48 hr of catheterization to restore or maintain patency of the artery, or documented occlusive arterial injury by radiologic study. RESULTS: 3,254 patients had 5,715 catheterization procedures, which included 3,859 arterial access events. 167 cases of AOAI were identified for an overall prevalence of 4.3% among arterial access events. Multiple logistic regression identified independent risk factors: weight category [<4 kg: odds ratio (OR) 4.5 (95% CI: 2.6-7.7), P < 0.001; 4-6 kg: OR 2.1 (1.3-3.5), P = 0.002, compared to 6-8 kg referent group]; largest catheter outer diameter French size [OR 1.6 (1.3-1.9), P < 0.001]; final activated clotting time (ACT) <250 sec [OR 1.9 (1.4-2.7), P < 0.001]; and need for arterial catheter exchange [OR 1.8 (1.02-3.2), P = 0.04]. CONCLUSIONS: AOAI occurred in 4.3% of pediatric cardiac catheterizations, and was most likely in smaller children and those with larger arterial catheters. Risk was also independently increased by arterial catheter exchange and having a final ACT <250 sec. These data act as an important benchmark and identify areas for intervention for future studies.