Glial Fibrillary Acid Protein and Cerebral Oxygenation in Neonates Undergoing Cardiac Surgery.

 Neonates undergoing surgery for complex congenital heart disease are at risk of developmental impairment. Hypoxic-ischemic brain injury might be a contributing factor. We aimed to investigate the perioperative release of the astrocyte cytoskeleton component glial fibrillary acid protein and its relation to cerebral oxygenation.  Serum glial fibrillary acid protein levels were measured before and 0, 12, 24, and 48 hours after surgery. Reference values were based on preoperative samples; concentrations above the 95th percentile were defined as elevated. Cerebral oxygenation was derived by near-infrared spectroscopy.  Thirty-six neonates undergoing 38 surgeries utilizing cardiopulmonary bypass were enrolled (complete data available for 35 procedures). Glial fibrillary acid protein was elevated after 18 surgeries (arterial switch: 7/12; Norwood: 5/15; others: 6/8; p = 0.144). Age at surgery was higher in cases with elevated serum levels (6 [4-7] vs. 4 [2-5] days, p = 0.009) and intraoperative cerebral oxygen saturation was lower (70 ± 10% vs. 77 ± 7%, p = 0.029). In cases with elevated postoperative glial fibrillary acid protein, preoperative cerebral oxygen saturation was lower for neonates undergoing the arterial switch operation (55 ± 9% vs. 64 ± 4%, p = 0.048) and age at surgery was higher for neonates with a Norwood procedure (7 [6-8] vs. 5 [4-6] days, p = 0.028).  Glial fibrillary acid protein was elevated after ∼50% of neonatal cardiac surgeries and was related to cerebral oxygenation and older age at surgery. The potential value as a biomarker for cerebral injury after neonatal cardiac surgery warrants further investigation; in particular, the association with neurodevelopmental outcome needs to be determined.

Hansen JH ，Kissner L ，Chitadze G ，Logoteta J ，Jung O ，Dütschke P ，Attmann T ，Scheewe J ，Kramer HH ... -  《-》

S100B and its relation to cerebral oxygenation in neonates and infants undergoing surgery for congenital heart disease.

Neonates and infants undergoing surgery for congenital heart disease are at risk for developmental impairment. Hypoxic-ischemic brain injury might be one contributing factor. We aimed to investigate the perioperative release of the astrocyte protein S100B and its relation to cerebral oxygenation. Serum S100B was measured before and 0, 12, 24, and 48 hours after surgery. Cerebral oxygen saturation was derived by near-infrared spectroscopy. S100B reference values based on preoperative samples; concentrations above the 75th percentile were defined as elevated. Patients with elevated S100B at 24 or 48 hours were compared to cases with S100B in the normal range. Neonates (≤28 days) and infants (>28 and ≤365 days) were analyzed separately due to age-dependent release of S100B. Seventy-four patients underwent 94 surgical procedures (neonates, n = 38; infants, n = 56). S100B concentrations were higher in neonates before and after surgery at all time points (P ≤ .015). Highest values were noticed immediately after surgery. Postoperative S100B was elevated after 15 (40.5%) surgeries in neonates. There was no difference in pre-, intra-, or postoperative cerebral oxygenation. In infants, postoperative S100B was elevated after 23 (41.8%) procedures. Preoperative cerebral oxygen saturations tended to be lower (53 ± 12% vs 59 ± 12%, P = .069) and arterial-cerebral oxygen saturation difference was higher (35 ± 11% vs 28 ± 11%, P = .018) in infants with elevated postoperative S100B. In the early postoperative course, cerebral oxygen saturation was lower (54 ± 13% vs 63 ± 12%, P = .011) and arterial-cerebral oxygen saturation difference was wider (38 ± 11% vs 30 ± 10%, P = .008). Cerebral oxygen saturation was also lower for the entire postoperative course (62 ± 18% vs 67 ± 9%, P = .047). Postoperative S100B was elevated in about 40% of neonates and infants undergoing cardiac surgery. Infants with elevated postoperative S100B had impaired perioperative cerebral tissue oxygenation. No relation between S100B and cerebral oxygenation could be demonstrated in neonates.

Hansen JH ，Kissner L ，Logoteta J ，Jung O ，Dütschke P ，Attmann T ，Scheewe J ，Kramer HH ... -  《-》

Perioperative cerebral oxygen saturation in neonates with hypoplastic left heart syndrome and childhood neurodevelopmental outcome.

Neonates with hypoplastic left heart syndrome have significant hemodynamic threats to cerebral perfusion and are at risk of reduced neurodevelopmental performance. We hypothesized that cerebral hypoxia, detectable by near-infrared spectroscopy in the early postoperative period, would be related to later neurodevelopmental performance. The study population was a sequential cohort of patients who had undergone stage 1 palliation of hypoplastic left heart syndrome under standard conditions, including neonatal perioperative monitoring with cerebral near-infrared spectroscopy, and who had undergone a neurodevelopmental assessment at age 4 to 5 years. The neonatal demographic and 48-hour perioperative hemodynamic parameters, including cerebral oxygen saturation, were tested for their relationship to 4 domains of neurodevelopmental performance, including visual-motor integration in childhood in univariate and multivariate models. The neurodevelopmental scores were classified as low if less than 85 (-1 standard deviation) and abnormal if less than 70 (-2 standard deviations). For the 51 patients in the surgical cohort, the early survival was 94%, the cumulative survival was 86%, and the neurodevelopmental assessment was completed by 21 (48%) of the survivors, without evidence of an ascertainment bias. At the test age of 56.3 ± 5.5 months, the composite neurodevelopmental index, constructed from equally weighted measures in 4 domains, was 97.6 ± 9.6, not different from the age-based norms, with 3 of 21 in the low range and none abnormal. The mean visual-motor integration was 93.4 ± 14, slightly less than the population norm (P < .05), with 2 of 21 having low scores and 1 abnormal scores. In patients with low to abnormal visual-motor integration, the perioperative stage 1 palliation cerebral oxygenation saturation was significantly lower (63.6 ± 8.1 vs 67.8 ± 8.1, P < .05). Two patients had discrete embolic strokes after their initial hospitalization; the occurrence of late stroke reduced the visual-motor integration performance but was not related to the early cerebral oxygen saturation. Nonlinear relationships of cerebral oxygen saturation to the neurodevelopmental measures found cerebral oxygen saturation thresholds of 49% to 62%. The hours at a cerebral oxygen saturation less than 45% and 55% were related to low visual-motor integration and neurodevelopmental index scores in the univariate and multivariate models. A multivariate model of age and weight at stage 1 palliation, cerebral oxygen saturation, arterial oxygen saturation, cardiopulmonary bypass and deep hypothermic circulatory arrest times, and later stroke predicted visual-motor integration to an important degree (R(2) = 0.53, P < .001). The actual and predicted visual-motor integration and neurodevelopmental index were normal when a cerebral oxygen saturation less than 45% and other risk conditions were avoided. Neurodevelopmental performance was related to demographic, neonatal perioperative physiologic, and later factors. Perioperative cerebral oxygenation assessed by near-infrared spectroscopy can detect hypoxic-ischemic conditions associated with injury and reduced neurodevelopmental performance and was the most significant physiologic factor identified. These data suggest that efforts to avoid cerebral hypoxia are likely to improve the outcomes in this high-risk population.

Hoffman GM ，Brosig CL ，Mussatto KA ，Tweddell JS ，Ghanayem NS ... -  《-》

Cerebral tissue oxygenation index and lactate at 24 hours postoperative predict survival and neurodevelopmental outcome after neonatal cardiac surgery.

There are no well-established noninvasive biomarkers for identifying patients at risk for poor outcome after surgery for congenital heart disease. Few studies have assessed prognostic accuracy of cerebral tissue oxygenation index (cTOI) measured by near infrared spectroscopy (NIRS). To assess the utility of noninvasive NIRS monitoring as a predictor of outcomes after neonatal cardiac surgery through measurement of cTOI. To examine the utility of noninvasive NIRS monitoring in combination with lactate concentration and inotropic score in prediction of outcomes after neonatal cardiac surgery. Prospective longitudinal cohort study. Operating room and cardiac intensive care unit, Children's National Heart Institute. Seventy-five patients with complex congenital heart disease undergoing surgical repair within first month of life. Cerebral TOI, blood lactate, and inotropic scores were measured preoperative, intraoperative and up to 24 hours postoperative. Postoperative mortality and neurodevelopmental outcome assessed by the Bayley Scales of Infant Development (BSID II). Mental and motor scores were obtained at 6, 15, and 21 months. Good outcome was defined as survival and BSID mental and motor scores ≥70 points. Poor outcome was defined as death or BSID scores <70 at most recent follow-up. Cohort of 75 patients prospectively followed including 40 patients with single ventricle and 35 with two ventricles. Four patients died before discharge and ten died within 21 months. Seven patients were lost to follow-up. Among survivors with follow-up (n = 54), BSID was abnormal in 25 (46%). Patients with poor outcome (n = 39) had lower mean cTOI 60 minutes off-CPB (48% vs. 58%, P = .003) and 24 hours postoperative (49% vs. 59%, P < .001), higher lactate (8.2 vs. 5.0 mmol/L, P = .005) and higher inotropic scores (10 vs. 6, P = .02) at 24 hours postoperative. ROC analysis indicated that cTOI had moderate predictive accuracy of outcome (AUC = 0.751, P < .001). Multivariable regression analysis confirmed that predictive accuracy was improved using both cTOI and lactate at 24 hours postoperative (AUC = 0.813, 95% CI: 0.705-0.921, P < .001) with optimal cutoff values <58% and >7.4 mmol/L, respectively (sensitivity = 95%). Cerebral TOI combined with lactate at 24 hours postoperative are accurate non-invasive predictive biomarkers of patient survival and neurodevelopmental outcome in neonates with CHD undergoing cardiac surgery.

Aly SA ，Zurakowski D ，Glass P ，Skurow-Todd K ，Jonas RA ，Donofrio MT ... -  《-》

Impaired cerebral autoregulation and elevation in plasma glial fibrillary acidic protein level during cardiopulmonary bypass surgery for CHD.

Easley RB ，Marino BS ，Jennings J ，Cassedy AE ，Kibler KK ，Brady KM ，Andropoulos DB ，Brunetti M ，Hogue CW ，Heitmiller ES ，Lee JK ，Spaeth J ，Everett AD ... -  《-》