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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Neuro-developmental outcome in single-ventricle patients: is the Norwood procedure a risk factor?

OBJECTIVES: Complex neonatal surgery is considered a risk factor for neuro-developmental impairment in single-ventricle patients. Neuro-developmental outcome was compared between preschool-aged Fontan patients who underwent a Norwood procedure and single-ventricle patients not requiring neonatal surgery with cardiopulmonary bypass. METHODS: Verbal, performance and full-scale intelligence quotient (IQ) were evaluated with the Wechsler Preschool and Primary Scale of Intelligence. Cognitive functions were assessed with the German 'Kognitiver Entwicklungstest für das Kindergartenalter' (KET-KID). Risk factors for impaired neuro-development were evaluated. RESULTS: Neuro-developmental assessment was completed in 95 patients (Norwood: n = 69; non-Norwood: n = 26). Median (interquartile range) IQ and KET-KID scores were in the normal range. Except for verbal KET-KID, scores did not differ between Norwood and non-Norwood patients (verbal IQ: 98 (86-105) vs 93 (85-102), P = 0.312; performance IQ: 91 (86-100) vs 96 (86-100), P = 0.932; full-scale IQ: 93 (86-101) vs 89 (84-98), P = 0.314; KET-KID verbal: 48 (17-72) vs 25 (2-54), P = 0.020; KET-KID non-verbal: 33 (18-62) vs 45 (15-54), P = 0.771; KET-KID global: 42 (14-65) vs 28 (6-63), P = 0.208). Full-scale IQ was below average (<85 points) in 14 (20%) Norwood and 9 (35%) non-Norwood cases (P = 0.181). Global KET-KID was below average (<16th percentile) in 19 (28%) and 10 (38%) patients (P = 0.326). Smaller head circumference z-score and complications before neonatal surgery were independently associated with lower scores. CONCLUSIONS: Neuro-developmental outcome of preschool-aged Fontan patients was in the normal range. The Norwood procedure was not a risk factor for neuro-developmental impairment. Preoperative condition and patient-related factors were more important determinants than variables related to surgical palliation.

Neurodevelopmental outcome in hypoplastic left heart syndrome: Impact of perioperative cerebral tissue oxygenation of the Norwood procedure.

OBJECTIVES: Patients with hypoplastic left heart syndrome are at risk for neurodevelopmental impairment. Hypoxic-ischemic brain injury during neonatal treatment might be a relevant cause. We evaluated the association between cerebral oxygenation in the perioperative course of the Norwood procedure and neurodevelopmental outcome. METHODS: Cerebral tissue oxygen saturation (ScO2) was obtained by near-infrared spectroscopy for 24 hours before and 48 hours after surgery in 43 patients. Full-scale, verbal, and performance IQ scores were evaluated with the Wechsler Preschool and Primary Scale of Intelligence at a median of 4.5 years (range, 3.5-6.8 years). Cognitive functions were assessed with the German Kognitiver Entwicklungstest für das Kindergartenalter (KET-KID). RESULTS: Mean IQ scores and KET-KID percentile ranks were in the lower-normal range (full-scale IQ, 94 ± 11; verbal IQ, 97 ± 13; performance IQ, 93 ± 9; KET-KID global, 42 ± 27; verbal, 48 ± 29; nonverbal, 37 ± 23). Scores were below average (full scale IQ <85 or KET-KID <16th percentile) in 12 cases. Mean preoperative ScO2 was lower in patients scoring below average (56.8% ± 7.1% vs 61.7% ± 5.8%; P = .028) and was correlated with full-scale IQ (r = 0.495; P = .001), verbal IQ (r = 0.524; P = .001), and performance IQ (r = 0.386; P = .012) scores, and with global (r = 0.360; P = .018) and verbal (r = 0.395, P = .009) KET-KID scores. A relationship between IQ or KET-KID scores and postoperative ScO2 was not found. Gestational age, head circumference z-score, age at surgery, and postoperative length of stay were associated with IQ and KET-KID scores. CONCLUSIONS: Neurodevelopmental outcome was in the lower-normal range. Along with innate patient factors, preoperative cerebral tissue oxygenation is likely an important determinant of cognitive development.

Impact of afterload reduction strategies on regional tissue oxygenation after the Norwood procedure for hypoplastic left heart syndrome.

OBJECTIVES: Low cerebral tissue oxygenation saturations have been observed by near-infrared spectroscopy (NIRS) after the Norwood procedure. Altered cerebral vascular resistance and pharmacological afterload reduction redirecting blood flow away from the cerebral circulation are possible mechanisms. METHODS: Two different afterload reduction strategies were evaluated in patients with hypoplastic left heart syndrome or variants after the Norwood procedure. In patients of Group 1 (n=34), afterload reduction was controlled with sodium nitroprusside or with the α-blocker phentolamine. In addition, a phosphodiesterase-III inhibitor was administered. Patients of Group 2 (n=34) received a phosphodiesterase-III inhibitor only. Cerebral and somatic tissue oxygenation saturations and routine intensive care monitoring data were recorded for 24 h before and 48 h after the Norwood procedure. Mean values of the last 4 preoperative (baseline) and of the first and last 4 postoperative hours (early and late course) were calculated. RESULTS: Baseline, early and late cerebral saturations were 58±7, 52±9 and 60±6% for Group 1 and 58±7, 52±12 and 61±7% for Group 2 and somatic saturations were 59±8, 76±10 and 67±9% and 58±9, 78±8 and 69±10%, respectively. Regional saturations were not different between groups. The postoperative cerebral tissue oxygen saturation was below 40% for 50 (0-1040) min in Group 1 and for 45 (0-720) min in Group 2 (P=1.00). Preoperative cerebral NIRS values (OR 0.85 [0.76-0.96], P=0.007), age at operation (OR 1.39 [1.02-1.88], P=0.034) and early postoperative diastolic blood pressure (OR 0.88 [0.78-0.99], P=0.038) were associated with cerebral tissue oxygen saturations below 40% for more than 60 min. Patients with a prolonged period of low cerebral tissue oxygen saturation had longer duration of mechanical ventilation (69 (37-192) vs 60 (33-238) h, P=0.039) and afterload reduction therapy was terminated later (95 (47-696) vs 74 (39-650) h, P=0.006). Early mortality was 9.4% (3 of 32) compared with 2.8% (1 of 36) in the remainder (P=0.336). CONCLUSIONS: The postoperative decline of cerebral tissue oxygen saturation was observed with both afterload reduction strategies. The difference between cerebral and somatic NIRS values may indicate a mismatch between cerebral and splanchnic oxygenation. Other strategies to improve cerebral tissue oxygenation are warranted.

Monitoring of regional tissue oxygenation with near-infrared spectroscopy during the early postoperative course after superior cavopulmonary anastomosis.

OBJECTIVES: Near-infrared spectroscopy (NIRS) offers continuous non-invasive monitoring of regional tissue oxygenation. We evaluated NIRS monitoring during the postoperative course after superior cavopulmonary anastomosis in patients with hypoplastic left heart syndrome and anatomically related malformations. METHODS: Cerebral (cSO(2)) and somatic (sSO(2)) tissue oxygenations were recorded for 48 h and compared with routine measures of intensive care monitoring. Changes in parameters in the case of postoperative complications were evaluated. RESULTS: Data were obtained from 32 patients. Median age at operation was 2.9 (1.5-10.0) months and weight was 5.3 ± 1.0 kg. Postoperative complications occurred in 7 patients (pulmonary artery thrombus n = 4, pneumothorax n = 1, cardiopulmonary resuscitation n = 1 and low-cardiac output n = 1). cSO(2) was 44 ± 14% at the end of the operation and reached its minimum of 40 ± 11% 2 h later (P = 0.018). Overall, cSO(2) was depressed early after surgery and increased from a mean of 42 ± 11% during the first 4 postoperative hours to 57 ± 8% in the last 4 h of the study period (P < 0.001). The sSO(2) decreased from 77 ± 11% during the early postoperative course to 68 ± 9% within the later course (P < 0.001). The cSO(2) correlated with the arterial partial pressure of oxygen (pO(2), r = 0.364, P < 0.001), with the arterial oxygen saturation (SaO(2), r = 0.547, P < 0.001) and with the central venous oxygen saturation providing the strongest correlation (SvO(2), r = 0.686, P < 0.001). Analysis of agreement between cSO(2) and SvO(2) measurements revealed a mean bias of 0.97 with limits of agreement between 19.8 and -17.9%. Inclusion of both cSO(2) and sSO(2) into a linear regression model slightly improved the prediction of SvO(2) from NIRS values (r = 0.706, P < 0.001). The mean values of cSO(2), sSO(2), SaO(2) and SvO(2) during the early postoperative period were lower in patients with complications (cSO(2): 45 ± 9 vs 29 ± 5%, P < 0.001; sSO(2): 80 ± 11 vs 70 ± 6%, P = 0.004; SaO(2): 76 ± 8 vs 66 ± 6%, P = 0.004; SvO(2): 48 ± 14 vs 32 ± 6%, P < 0.001). CONCLUSIONS: NIRS technology allows inferring the global oxygenation from continuous non-invasive measurements of regional tissue oxygenation. The cSO(2) is lowered in the early postoperative course. Lower cSO(2) values in the early postoperative course may be predictive of postoperative complications.

Perioperative cerebral and somatic oxygenation in neonates with hypoplastic left heart syndrome or transposition of the great arteries.

OBJECTIVE: Significant depression in cerebral oxygen saturation has been observed in patients with hypoplastic left heart syndrome (HLHS) undergoing Norwood operations. We monitored cerebral oxygen saturation with near-infrared spectroscopy before and after this procedure. Patients with transposition of great arteries (TGA) before and after arterial switch operation were also studied to elucidate whether post-cardiopulmonary bypass (CPB) changes in cerebral oxygen saturation are related to CPB or hemodynamic alterations inherent in single-ventricle physiology. METHODS: We monitored 33 patients with HLHS and 20 with TGA 24 hours before and 48 hours after CPB. In addition to cerebral oxygen saturation, routine measurements of oxygen transport and delivery were performed. RESULTS: Preoperatively, cerebral oxygen saturation was higher in patients with HLHS than with TGA (61% ± 7% vs 56% ± 8%, P = .04). After CPB, cerebral oxygen saturation was markedly depressed in both groups but increased toward end of monitoring (HLHS vs TGA minimal value 42% ± 12% vs 54% ± 11%, P < .001, value 48 hours after CPB 62% ± 7% vs 80% ± 8%, P < .0001). Routine measures of oxygen delivery, such as arterial and central venous oxygen saturations, were similar at minimal cerebral oxygen saturation and 48 hours after CPB. CONCLUSIONS: Depression of cerebral oxygen saturation is prevalent among neonates with congenital heart disease regardless of whether univentricular or biventricular circulation is present, suggesting that cerebral desaturation is mainly induced by CPB's effect on cerebral blood flow. Routine measures of oxygen delivery fail to indicate cerebral desaturation.

Risk factors for adverse outcome after superior cavopulmonary anastomosis for hypoplastic left heart syndrome.

OBJECTIVE: Outcome of staged palliation for hypoplastic left heart syndrome (HLHS) has improved over the past decades. We sought to evaluate the outcome of the second palliative procedure, the superior cavopulmonary anastomosis (SCPA), in a single-centre cohort and to identify risk factors for adverse outcome. METHODS: Full data on all 119 HLHS patients who underwent SCPA in our centre between January 1996 and December 2007 were analysed. RESULTS: Early adverse outcome (death or cardiac transplant within 30 days after surgery or before hospital discharge) was 3.4%. Late adverse outcome (death or transplant after hospital discharge but before the next operative procedure) was 8.7%. Postoperative complications occurred in 30% of patients (n = 36), with transient arrhythmia (n = 11; 9%) and pulmonary artery stenosis or thrombosis (n = 10; 8%) being the most common. The presence of more than moderate tricuspid valve regurgitation after surgery proved to be a strong predictor of late adverse outcome (odds ratio (OR) 16.5 (4.4-62.6), P < 0.001). SCPA at less than 4 months of age did not increase the risk for adverse outcome (OR 1.2 (0.4-3.6), P = 0.78) but increased the risk for postoperative complications (OR 6.3 (2.3-14.9), P < 0.001). CONCLUSIONS: SCPA can nowadays be performed in HLHS patients with low mortality. However, more than moderate tricuspid valve regurgitation should be targeted at surgery as it is a risk factor for adverse outcome such as death or need for cardiac transplant. SCPA should ideally be performed in children older than 4 months to minimise the risk of postoperative complications.

The impact of afterload reduction on the early postoperative course after the Norwood operation - a 12-year single-centre experience.

OBJECTIVE: The objective of this study was to analyse the postoperative course and early outcome after the Norwood operation for patients with hypoplastic left heart syndrome. We particularly aimed to assess the impact of surgical and pharmacological modifications introduced. METHODS: Of 157 patients who underwent the Norwood operation between January 1996 and December 2007, postoperative intensive care data on haemodynamics, pharmacological support and ventilation were analysed from 146 patients (six patients died intra-operatively and data were incomplete in five). The cohort was divided into three groups depending on the surgical method and type of afterload reduction. Patients of group 1 (n=39, January 1996-December 1999) were operated with deep hypothermic circulatory arrest. In patients of group 2 (n=59, January 2000-June 2003) and group 3 (n=59, July 2003-December 2007) antegrade selective cerebral perfusion was used. Patients of groups 1 and 2 received sodium nitroprusside to reduce afterload; in group 3 phentolamine was used. RESULTS: There were no differences between the groups in terms of preoperative status and anatomy, except a higher incidence of prenatal diagnosis between groups 3 and 1. The duration and dosage of sodium nitroprusside administration were similar in groups 1 and 2. The median duration of afterload reduction was significantly longer in group 3 compared with both the other groups (72 h (range: 24-201 h) vs 48 h (range: 8-145 h) and 48 h (range: 4-173 h), respectively). The median ventilation times was shorter in group 2 compared with group 1 (61 h (range: 16-1191 h) vs 119 h (range: 26-648 h)). During the first 36 postoperative hours, the mean arterial blood pressure and coronary perfusion pressure were significantly lower in group 3 than in group 1 (50.7+/-4.8 and 28+/-3.7 mmHg vs 53.6+/-5.2 and 31.4+/-4.3 mmHg), but, in patients of group 3, the time period to consistently reach a mean arteriovenous oxygen difference below 5 ml dl(-1) was markedly shorter than in the other groups (group 3: 12h 4.90+/-1.97 ml dl(-1); group 1: 24h 4.53+/-2.25 ml dl(-1) and group 2: 24h 4.57+/-2.04 ml dl(-1)). Complication rates were similar between the groups. However, 30-day mortality decreased over the study period to an exponentially weighted moving average of 2.3%. CONCLUSION: Adamant afterload reduction improves systemic blood flow early after the Norwood operation and may have contributed to the reduction in early postoperative mortality achieved over 12 years.

Outcome of the Norwood operation in patients with hypoplastic left heart syndrome: a 12-year single-center survey.

OBJECTIVE: Recent advances in perioperative care have led to a decrease in mortality of children with hypoplastic left heart syndrome undergoing the Norwood operation. This study aimed to evaluate the outcome of the Norwood operation in a single center over 12 years and to identify clinical and anatomic risk factors for adverse early and longer term outcome. METHODS: Full data on all 157 patients treated between 1996 and 2007 were analyzed. RESULTS: Thirty-day mortality of the Norwood operation decreased from 21% in the first 3 years to 2.5% in the last 3 years. The estimated exponentially weighted moving average of early mortality after 157 Norwood operations was 2.3%. Risk factors were an aberrant right subclavian artery, the use and duration of circulatory arrest, and the duration of total support time. The anatomic subgroup mitral stenosis/aortic atresia and female gender tended to show an increased early mortality. In the group of patients who required postoperative cardiopulmonary resuscitation, the ascending aorta was significantly smaller than in the remainder (3.03 +/- 1.05 vs 3.63 +/- 1.41 mm). Interstage mortality was 15% until the initiation of a home surveillance program in 2005, which has zeroed it so far. It was significantly higher in the mitral stenosis/aortic atresia subgroup and tended to be higher in patients who required cardiopulmonary resuscitation after the Norwood operation. The best actuarial survival was observed in the mitral atresia/aortic atresia subgroup. CONCLUSION: The Norwood operation can now be performed with low mortality. Patients with mitral stenosis/aortic atresia still constitute the most challenging subgroup.

Restrictive enlargement of the pulmonary annulus at surgical repair of tetralogy of Fallot: 10-year experience with a uniform surgical strategy.

OBJECTIVES: Retrospective data suggest that a wide pulmonary annulus after Fallot repair aggravates pulmonary regurgitation. Therefore, since 1997, in our institution transannular patch enlargement was only intended for patients with a native pulmonary annulus z-score less than -4. If transannular patching was needed, enlargement was aimed to diameters within the range of a z-score of -2. We sought to determine whether this strategy of restrictive enlargement of the pulmonary annulus was adequate to reduce transannular patch rate and to limit pulmonary annulus width without increased right ventricular pressure load. METHODS: Two-hundred-and-sixteen Fallot patients were retrospectively analysed. Ninety-eight patients underwent repair between 1997 and 2006 adhering to our uniform strategy (Group 1). One hundred and eighteen patients were operated between 1977 and 1996 without a uniform strategy (Group 2). Transannular patch rate, native and postoperative pulmonary annulus z-score, postoperative right ventricular outflow tract velocity on echocardiography and early reoperation rate for right ventricular outflow tract obstruction were analysed in both groups. RESULTS: Compared to Group 2, patients in Group 1 were younger at repair, transannular patch rate was significantly reduced (32 vs 68%, p<0.0001) and postoperative pulmonary annulus diameters were smaller (z-score -2.1+/-1.5 vs 0.0+/-3.1, p<0.0001). However, no difference in right ventricular outflow tract velocity (2.4+/-0.8 vs 2.2+/-0.8m/s; p=NS) or the incidence of early reoperation for right ventricular outflow tract obstruction was found between the groups (3/98 vs 1/118; p=NS). CONCLUSION: Restrictive enlargement of the pulmonary annulus at Fallot repair lowers transannular patch rate, limits the postoperative width of the pulmonary annulus but does not result in increased right ventricular pressure load or reoperation rate for residual right ventricular outflow tract obstruction. A limitation of postoperative pulmonary regurgitation can be expected when the extent of pulmonary annulus enlargement at repair is limited.

Impact of preoperative treatment strategies on the early perioperative outcome in neonates with hypoplastic left heart syndrome.

OBJECTIVE: This study was undertaken to determine the impact of specific intensive care procedures on preoperative hemodynamics, incidence of preoperative organ dysfunction, and in-hospital mortality among neonates with hypoplastic left heart syndrome with pulmonary overcirculation and to assess the influence of the change in preoperative management on early postoperative outcome. METHODS: In this retrospective evaluation of 72 neonates with classic hypoplastic left heart syndrome and severe pulmonary overcirculation with different preoperative management strategies from 1992 to 1995 and from 1996 to 2000, univariate and multivariate analyses of risk factors were performed with stepwise logistic regression. RESULTS: Among patients with ventilatory and inotropic support from admission until surgery, degree of metabolic acidosis (lowest recorded and prerepair pH values) was significantly higher than among patients who received systemic vasodilators without ventilation before surgery. Preoperative organ dysfunction occurred in 19 of 72 patients (26%), predominantly before 1996; the most significant was hepatic failure in 13 (68%). Lowest recorded and prerepair pH values did not predict the development of organ dysfunction, whereas inotropic medication, lack of afterload reduction, and especially ventilatory support correlated significantly with organ injury. In-hospital mortality decreased from 65% (13/20) to 13% (6/46) from the first to the second period. According to multivariate analysis, ventilatory support and organ dysfunction were significantly related to in-hospital mortality. CONCLUSION: In neonates with hypoplastic left heart syndrome, systemic afterload reduction can avoid preoperative artificial respiration, identified as a significant risk factor for the development of preoperative dysfunction of end organs and in-hospital mortality.