Echocardiographic measured shunt velocity does not predict pulmonary blood flow in patients with Blalock-Thomas-Taussig shunt.

INTRODUCTION: Catheterisation is the gold standard used to evaluate pulmonary blood flow in patients with a Blalock-Thomas-Taussig shunt. It involves risk and cannot be performed frequently. This study aimed to evaluate if echocardiographic measurements obtained in a clinical setting correlate with catheterisation-derived pulmonary blood flow in patients with a Blalock-Thomas-Taussig shunt as the sole source of pulmonary blood flow. METHODS: Chart review was performed retrospectively on consecutive patients referred to the catheterisation lab with a Blalock-Thomas-Taussig shunt. Echocardiographic parameters included peak, mean, and diastolic gradients across the Blalock-Thomas-Taussig shunt and forward and reverse velocity time integral across the distal transverse aorta. In addition to direct correlations, we tested a previously published formula for pulmonary blood flow calculated as velocity time integral across the shunt × heart rate × Blalock-Thomas-Taussig shunt area. Catheterisation parameters included pulmonary and systemic blood flow as calculated by the Fick principle. RESULTS: 18 patients were included. The echocardiography parameters and oxygen saturation did not correlate with catheterisation-derived pulmonary blood flow, systemic blood flow, or the ratio of pulmonary to systemic blood flow. As the ratio of reverse to forward velocity time integral across the transverse aorta increased, the probability of shunt stenosis decreased. CONCLUSION: Echocardiographic measurements obtained outside the catheterisation lab do not correlate with catheterisation-derived pulmonary blood flow. The ratio of reverse to forward velocity time integral across the transverse aortic arch may be predictive of Blalock-Thomas-Taussig shunt narrowing; this finding should be investigated further.

Urine Quantification Following Furosemide for Severe Acute Kidney Injury Prediction in Critically Ill Children.

A standardized, quantified assessment of furosemide responsiveness predicts acute kidney injury (AKI) in children after cardiac surgery and AKI progression in critically ill adults. The purpose of this study was to determine if response to furosemide is predictive of severe AKI in critically ill children outside of cardiac surgery. We performed a multicenter retrospective study of critically ill children. Quantification of furosemide response was based on urine flow rate (normalized for weight) measurement 0 to 6 hours after the dose. The primary outcome was presence of creatinine defined severe AKI (Kidney Disease Improving Global Outcomes stage 2 or greater) within 7 days of furosemide administration. Secondary outcomes included mortality, duration of mechanical ventilation and length of stay. A total of 110 patients were analyzed. Severe AKI occurred in 20% ( n = 22). Both 2- and 6-hour urine flow rate were significantly lower in those with severe AKI compared with no AKI ( p = 0.002 and p < 0.001). Cutoffs for 2- and 6-hour urine flow rate for prediction of severe AKI were <4 and <3 mL/kg/hour, respectively. The adjusted odds of developing severe AKI for 2-hour urine flow rate of <4 mL/kg/hour was 4.3 (95% confidence interval [CI]: 1.33-14.15; p = 0.02). The adjusted odds of developing severe AKI for 6-hour urine flow rate of <3 mL/kg/hour was 6.19 (95% CI: 1.85-20.70; p = 0.003). Urine flow rate in response to furosemide is predictive of severe AKI in critically ill children. A prospective assessment of urine flow rate in response to furosemide for predicting subsequent severe AKI is warranted.

Methylprednisolone for Heart Surgery in Infants - A Randomized, Controlled Trial.

BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes. RESULTS: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001). CONCLUSIONS: Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).

Vitamin therapy in sepsis.

Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B1), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B2, B6, B12, and E. IMPACT: Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.

Using next generation sequencing of alpine plants to improve fecal metabarcoding diet analysis for Dall's sheep.

OBJECTIVES: Dall's sheep (Ovis dalli dalli) are important herbivores in the mountainous ecosystems of northwestern North America, and recent declines in some populations have sparked concern. Our aim was to improve capabilities for fecal metabarcoding diet analysis of Dall's sheep and other herbivores by contributing new sequence data for arctic and alpine plants. This expanded reference library will provide critical reference sequence data that will facilitate metabarcoding diet analysis of Dall's sheep and thus improve understanding of plant-animal interactions in a region undergoing rapid climate change. DATA DESCRIPTION: We provide sequences for the chloroplast rbcL gene of 16 arctic-alpine vascular plant species that are known to comprise the diet of Dall's sheep. These sequences contribute to a growing reference library that can be used in diet studies of arctic herbivores.

Neurocognitive and behavioural profile in Panayiotopoulos syndrome.

AIM: To determine neurocognitive performance and behavioural problems in children with Panayiotopoulos syndrome. METHOD: All 18 children (10 females, 8 males; mean age 4y 7mo; SD 1y 10mo) diagnosed with Panayiotopoulos syndrome at the Kempenhaeghe Epilepsy Center in the Netherlands between 2010 and 2017 were analysed retrospectively. All underwent a neuropsychological/behavioural assessment, an academic assessment, and a 24-hour electroencephalogram. RESULTS: Mean full-scale IQ (93.5; range 76-123; p=0.04) and performance IQ (93.2; range 76-126; p=0.04) were within the normal range, although significantly lower compared to the normative mean. Verbal IQ (96.3; range 76-118) and processing speed (96.1; range 74-114) were not significantly lower. Simple auditory/visual reaction times, visual attention, visual-motor integration, and verbal memory were significantly lower compared to normative values. On average, patients with Panayiotopoulos syndrome were 8 months behind in arithmetic speed and 11 months behind in reading speed for the number of months in school. Behavioural questionnaires revealed significantly higher scores on reported internalizing behavioural problems. INTERPRETATION: Children with Panayiotopoulos syndrome demonstrated diffuse cognitive dysfunction in full-scale IQ, performance IQ, visual attention, visual-motor integration, and verbal memory. A high incidence of internalizing behavioural problems was reported. This strongly suggests neuropsychological and behavioural comorbidity in children with Panayiotopoulos syndrome. WHAT THIS PAPER ADDS: Children with Panayiotopoulos syndrome are at risk for cognitive deficits in various cognitive domains. Children with Panayiotopoulos syndrome are also prone to internalizing behavioural problems. Mild-to-severe academic underachievement was present in more than half of the children with Panayiotopoulos syndrome.

Functional brain network characteristics are associated with epilepsy severity in childhood absence epilepsy.

While cognitive impairments are not generally considered to be part of the childhood absence epilepsy (CAE) syndrome, some recent studies report cognitive, mainly attentional, deficits. Here we set out to investigate the whole brain functional network of children with CAE and controls. Furthermore, the possible relation of the functional network abnormalities with epilepsy and neurocognitive characteristics is studied. Seventeen children with childhood CAE (aged 9.2 ±â€¯2.1 years) and 15 controls (aged 9.8 ±â€¯1.8 years) were included. Resting state functional MRI was acquired to study the functional network. Using graph theoretical analysis, three global metrics of the functional network were investigated: the characteristic path length, the clustering coefficient, and the small-worldness. A multivariable linear regression model including age, sex, and subject motion as covariates was used to investigate group differences in the graph metrics. Subsequently, relations of the graph metrics with epilepsy and neurocognitive characteristics were assessed. Longer path lengths, weaker clustering and a lower small-world network topology were observed in children with CAE compared to controls. Moreover, longer path lengths were related to a longer duration of CAE and a higher number of absence seizure per hour. Clustering and small-worldness were not significantly related to epilepsy or neurocognitive characteristics. The organization of the functional network of children with CAE is less efficient compared to controls, and is related to disease duration. These preliminary findings suggest that CAE is associated with alterations in the functional network.

Hyperlactatemia: An Update on Postoperative Lactate.

While hyperlactatemia in postoperative cardiac surgery patients was once believed to solely reflect hypoperfusion, either from the accumulated "oxygen debt" during bypass or ongoing inadequate perfusion, our understanding of lactate generation, clearance, and management has evolved. A contemporary understanding of lactate balance is critical to the management of the postoperative patient with hyperlactatemia. In this review, we summarize the current understanding of lactate metabolism in pediatric patients following cardiac surgery and highlight two types of hyperlactatemia: type A, which is secondary to inadequate oxygen delivery and tissue hypoxia, and type B, which in postoperative pediatric cardiac surgery patients largely reflects increased glycolysis driven by the stress response. Both types may coexist; thus, it is imperative that providers first assess the patient for evidence of hypoperfusion. In patients with evidence of adequate perfusion, a type B component is often associated with a concomitant balanced (normal anion gap) metabolic acidosis and hyperglycemia. These patients will benefit from a more nuanced approach to their type B hyperlactatemia, as many will have a benign course and may be managed expectantly.

Constructing an Axonal-Specific Myelin Developmental Graph and its Application to Childhood Absence Epilepsy.

BACKGROUND AND PURPOSE: The process of myelination starts in utero around 20 weeks of gestation and continues through adulthood. We first set out to characterize the maturation of the tract-specific myelin content in healthy subjects from childhood (7-12 years) into adulthood (18-32 years). Second, we apply the resulting development graph to children with childhood absence epilepsy (CAE), a pediatric epilepsy that was previously characterized by changes in myelin content. METHODS: In a prospective cross-sectional study, 15 healthy children (7-12 years), 14 healthy adult participants (18-32 years) and 17 children with a clinical diagnosis of CAE (6-12 years) were included. For each participant, diffusion weighted images were acquired to reconstruct bundles of white matter tracts and multi-echo multi-slice GRASE images were acquired for myelin-water estimation. Subsequently, a tract-specific myelin development graph was constructed using the percentual difference in myelin-water content from childhood (12 year) to adulthood (25 year). RESULTS: The graph revealed myelination patterns, where tracts in the central regions myelinate prior to peripheral tracts and intra-hemispheric tracts as well as tracts in the left hemisphere myelinate prior to inter-hemispheric tracts and tracts in the right hemisphere, respectively. No significant differences were found in myelin-water content between children with CAE and healthy children for neither the early developing tracts, nor the tracts that develop in a later stage. However, the difference between the myelin-water of late and early developing tracts is significantly smaller in the children with CAE. CONCLUSION: These results indicate that CAE is associated with widespread neurodevelopmental myelin differences.

Correction to: Towards a Better Understanding of Cognitive Deficits in Absence Epilepsy: a Systematic Review and Meta-Analysis.

Due to an error during the editorial phase, a correction regarding Fig. 2 is added to the original article: "Towards a Better Understanding of Cognitive Deficits in Absence Epilepsy: a Systematic Review and Meta-Analysis". Please see below correct Fig. 2.

Towards a Better Understanding of Cognitive Deficits in Absence Epilepsy: a Systematic Review and Meta-Analysis.

Cognition in absence epilepsy (AE) is generally considered undisturbed. However, reports on cognitive deficits in AE in recent years have suggested otherwise. This review systematically assesses current literature on cognitive performance in children with AE. A systematic literature search was performed in Pubmed, Embase, Cochrane and Web of Science. All studies reporting on cognitive performance in children with AE were considered. In total 33 studies were eligible for inclusion. Neuropsychological tests were classified into the following domains: intelligence; executive function; attention; language; motor & sensory-perceptual examinations; visuoperceptual/visuospatial/visuoconstructional function; memory and learning; achievement. Random-effect meta-analyses were conducted by estimating the pooled mean and/or pooling the mean difference in case-control studies. Full-scale IQ in children with AE was estimated at 96.78 (95%CI:94.46-99.10) across all available studies and in case-control studies IQ was on average 8.03 (95%CI:-10.45- -5.61) lower. Verbal IQ was estimated at 97.98 (95%CI:95.80-100.16) for all studies and 9.01 (95%CI:12.11- -5.90) points lower in case-control studies. Performance IQ was estimated at 97.23 (93.24-101.22) for all available studies and 5.32 (95%CI:-8.27-2.36) points lower in case-control studies. Lower performance was most often reported in executive function (cognitive flexibility, planning, and verbal fluency) and attention (sustained, selective and divided attention). Reports on school difficulties, neurodevelopmental problems, and attentional problems were high. In conclusion, in contrast to common beliefs, lower than average neurocognitive performance was noted in multiple cognitive domains, which may influence academic and psychosocial development.

Lower myelin-water content of the frontal lobe in childhood absence epilepsy.

OBJECTIVE: The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. METHODS: Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. RESULTS: The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P > 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. SIGNIFICANCE: The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.

Cognitive development in absence epilepsy during long-term follow-up.

Absence epilepsy (AE) has been associated with lower than average cognitive functioning, which are clinically relevant in some and may predispose to problems later in life. This study aimed to assess cognitive development during long-term follow-up in children with AE. Thirty-one children with AE, who had undergone two neuropsychological assessments between 2010 and 2017 were analyzed retrospectively. Cognitive measurements were 1.7 ± 0.95 years apart. The difference in neurocognitive test scores was assessed on a group level and on an individual level using reliable change methodology. Results show that sustained attention was lower at the first measurement compared to the normative mean. Sustained attention improved during follow-up and 7 out of 14 children showed improvement after correction for practice effects. Receptive vocabulary showed a decline over time, but did not differ from the normative mean. Significant lower mean group scores were present for performance IQ, perceptual organization, processing speed, simple reaction times, and visual motor integration, while being stable over time in the majority of children. Cognitive development was not associated with seizure freedom. Mild-to-severe academic underachievement was present in 65% and comorbidities that might affect learning in 38%. This study in children with AE showed improvement in sustained attention during long-term follow-up while other cognitive weaknesses persisted over time, regardless of seizure freedom.

Furosemide response predicts acute kidney injury in children after cardiac surgery.

OBJECTIVE: A standardized assessment of response to furosemide is predictive of acute kidney injury progression in adults, but a paucity of data exists in pediatric patients. We evaluate furosemide responsiveness in a multicenter cohort of pediatric patients after cardiac surgery. METHODS: Children who underwent cardiac surgery with a Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery score of 3 or greater were retrospectively identified. The first dose of furosemide after surgery was recorded, and hourly urine output for 6 hours was recorded after the index dose. Urine flow rate calculated as urine output per hour was used to predict development of acute kidney injury. RESULTS: A total of 166 patients from 4 institutions (median age, 6.3 months; interquartile range, 0.4-27.7) were included. Acute kidney injury occurred in 54 patients (33%). Compared with those without acute kidney injury, the 2- and 6-hour urine flow rates were significantly lower in patients in whom acute kidney injury developed: 2.9 (0.9-6.5) versus 5.0 (2.5-9.0) mL/kg/h for 2-hour urine flow rate, P = .004, and 2.4 (1.2-4.0) versus 4.0 (2.3-5.9) mL/kg/h for 6-hour flow rate, P = .001. In multivariable regression analysis, 2-hour (odds ratio, 1.2, P = .002) and 6-hour (odds ratio, 1.40, P < .001) urine flow rates were independently associated with acute kidney injury development. Lower urine flow rate at both 2 and 6 hours was also independently associated with longer hospital length of stay. CONCLUSIONS: Lower urine flow rate after furosemide administration, when evaluated in a heterogeneous cohort of children from multiple institutions after pediatric cardiac surgery, was independently associated with subsequent acute kidney injury and longer length of stay. Future prospective studies are needed to validate furosemide responsiveness as a predictor of acute kidney injury.

Total and free cortisol responses and their relation to outcomes after cardiopulmonary bypass in infants.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be partially responsible for the hemodynamic instability experienced by infants after cardiopulmonary bypass (CPB). We report the full spectrum of the HPA response surrounding CPB for infant congenital cardiac surgery. METHODS: We enrolled 84 infants who received 1 mg/kg of dexamethasone before initiation of CPB. Total cortisol (TC), free cortisol (FC), adrenocorticotropic hormone (ACTH), and corticosteroid-binding globulin (CBG) were measured at 3 time points: immediately before CPB (TP1), on intensive care unit arrival (TP2), and at 24 hours after surgery (TP3). A 1-µg ACTH stimulation test was performed at each time point to evaluate adrenal responsiveness. RESULTS: Sixty-eight infants completed all study procedures. Levels of TC, FC, CBG, and ACTH decreased significantly between the preoperative and 24-hour postoperative measurements. There were no significant associations between preoperative FC responses and clinical outcomes after adjusting for weight and Risk-Adjusted Scores for Congenital Heart Surgery. Infants with subnormal TC responses to ACTH stimulation (<9 µg/dL) at TP2 had greater fluid requirements (P < .001) and greater chest tube output (P < .001) during the first 24 hours, as well as longer length of stay (LOS) (P = .007). Except for LOS, these differences persisted for infants with subnormal stimulation tests at TP3. CONCLUSIONS: We observed a significant decline in all aspects of the HPA axis throughout the first 24 hours after infant CPB. TC and FC levels were not associated with clinical outcomes. Subnormal (Δ <9 µg/dL) TC response to cosyntropin stimulation during the postoperative period was associated with increased fluid resuscitation and greater LOS.

Fluid Management: Pharmacologic and Renal Replacement Therapies.

OBJECTIVES: Focusing on critically ill children with cardiac disease, we will review common causes of fluid perturbations, clinical recognition, and strategies to minimize and treat fluid-related complications. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Meticulous fluid management is vital in critically ill children with cardiac disease. Fluid therapy is important to maintain adequate blood volume and perfusion pressure in order to support cardiac output, tissue perfusion, and oxygen delivery. However, fluid overload and acute kidney injury are common and are associated with increased morbidity and mortality. Understanding the etiologies for disturbances in volume status and the pathophysiology surrounding those conditions is crucial for providing optimal care.

Pathophysiology of Post-Operative Low Cardiac Output Syndrome.

Low cardiac output syndrome frequently complicates the post-operative care of infants and children following cardiac surgery. The onset of low cardiac output follows a predictable course in the hours following cardiopulmonary bypass, as myocardial performance declines in the face of an elevated demand for cardiac output. When demand outstrips supply, shock ensues, and early recognition and intervention can decrease mortality. Multifactorial in etiology, this article will discuss the pathophysiology of low cardiac output syndrome, including myocardial depression following bypass, altered cardiac loading conditions, and inflammation driving a hypermetabolic state. Contributions from altered neurohormonal, thyroid, and adrenal axes will also be discussed. Sources included the clinical experiences of four cardiac intensivists, supported throughout by primary sources and relevant reviews obtained through PubMed searches and from seminal textbooks in the field. This article addresses the second of eight topics comprising the special issue entitled "Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery".