Altered metabolic and inflammatory transcriptomics after cardiac surgery in neonates with congenital heart disease.

The study examines the whole blood transcriptome profile before and after cardiopulmonary bypass (CPB) in neonates with hypoplastic left heart syndrome (HLHS), a severe form of congenital heart disease, that can develop low cardiac output syndrome (LCOS). Whole blood mRNA transcriptome profiles of 13 neonates with HLHS before and after their first palliative surgery were analyzed to determine differentially expressed genes and pathways. The median age and weight at surgery were 4 days and 3.2 kg, respectively. Of the 13 patients, 8 developed LCOS. There was no significant difference between CPB, aortic cross clamp, deep hypothermic cardiac arrest times between patients that develop LCOS and those that do not. Upon comparing differential gene expression profiles between patients that develop LCOS and those that do not in pre-operative samples, 1 gene was up-regulated and 13 were down regulated. In the post-operative samples, 4 genes were up-regulated, and 4 genes were down regulated when patients that develop LCOS were compared to those that do not. When comparing post-operative samples to pre-operative samples in the patients that do not develop LCOS, 1484 genes were up-regulated, and 1388 genes were down regulated; while patients that developed LCOS had 2423 up-regulated genes, and 2414 down regulated genes for the same pre to post-operative comparison. Pathway analysis revealed differential regulation of inflammatory pathways (IL signaling, PDGF, NOTCH1, NGF, GPCR) and metabolic pathways (heme metabolism, oxidative phosphorylation, protein metabolism including amino acid and derivatives, fatty acid metabolism, TCA cycle and respiratory electron transport chain). By identifying altered transcriptome profiles related to inflammation and metabolism in neonates with HLHS who develop LCOS after CPB, this study opens for exploration novel pathways and potential therapeutic targets to improve outcomes in this high-risk population.

Interstage Home Monitoring for Infants With Single Ventricle Heart Disease: Education and Management: A Scientific Statement From the American Heart Association.

This scientific statement summarizes the current state of knowledge related to interstage home monitoring for infants with shunt-dependent single ventricle heart disease. Historically, the interstage period has been defined as the time of discharge from the initial palliative procedure to the time of second stage palliation. High mortality rates during the interstage period led to the implementation of in-home surveillance strategies to detect physiologic changes that may precede hemodynamic decompensation in interstage infants with single ventricle heart disease. Adoption of interstage home monitoring practices has been associated with significantly improved morbidity and mortality. This statement will review in-hospital readiness for discharge, caregiver support and education, healthcare teams and resources, surveillance strategies and practices, national quality improvement efforts, interstage outcomes, and future areas for research. The statement is directed toward pediatric cardiologists, primary care providers, subspecialists, advanced practice providers, nurses, and those caring for infants undergoing staged surgical palliation for single ventricle heart disease.

Neutrophil-lymphocyte ratio as a mortality predictor for Norwood stage I operations.

BACKGROUND: Hypoplastic left heart syndrome is a lethal congenital heart malformation when untreated resulting in a 95% mortality in the first month of life. In this study, we aimed to investigate the newly introduced inflammatory biomarker, neutrophil-lymphocyte ratio, as a mortality predictor in postoperative hypoplastic left heart syndrome patients. METHODS: Patients were divided into two groups; Group 1 consisted of 33 patients who were discharged and Group 2 including 20 patients who were deceased following surgery. Patients' preoperative demographic characteristics, total white blood cell counts, neutrophil counts, lymphocyte counts, neutrophil-lymphocyte ratio, C-reactive proteins, alanine aminotransferase, aspartate transaminase, urea, and creatinine levels were recorded. Studys' primary endpoint was all-cause patient mortality following surgery. RESULTS: The preoperative neutrophil-lymphocyte ratio was found to be significantly different between the groups (p = 0.001). High neutrophil-lymphocyte ratio was found to be associated with an increased risk of death. The ROC curves of neutrophil-lymphocyte ratio were found to be associated with mortality. The area under curve for the preoperative neutrophil-lymphocyte ratio was 0.74. Neutrophil-lymphocyte ratio predicted mortality with a sensitivity of 78% and a specificity of 65%. CONCLUSION: Neutrophil-lymphocyte ratio can contribute to the early identification of patients at high risk for complications. In addition, through the use of NLR, clinicians could implement measures for the optimal therapeutic approach of cardiac surgery patients and the elimination of adverse patient outcomes.

The association of maternal lymphatic markers and critical congenital heart defects in the fetus-A population based case-control study.

The objective ot this study was to investigate whether lymphatic markers measured in women during the second trimester are associated with critical congenital heart defects (CCHDs) in offspring. This is a retrospective cohort study of pregnant women who participated in the California Prenatal Screening Program. CCHD data in the offspring was captured by linking birth certificate data with hospital patient discharge records. Second trimester samples were assayed for vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) AA/BB, and PDGF AB. Logistic models were used to evaluate the association between lymphatic biomarkers and CCHD. Models were adjusted for other serum biomarkers and maternal characteristics. Results are presented in odds ratios (OR) with 95% confidence intervals (CI). We identified 93 cases with CCHDs and 194 controls without CCHDs. The crude and adjusted OR for log (ln) VEGF was 1.07 (95%CI 0.94-1.22) and 1.08 (95%CI 0.94-1.24), respectively; for ln PDGF AB/BB was 0.93 (95%CI 0.6-1.35) and 0.58 (95%CI 0.32-1.05), respectively. There was a significant association between ln PDFG AA and CCHDs (crude OR 1.83 (95%CI 1.05-3.2); adjusted OR 2.41 (95%CI 1.06-5.44)). Levels of circulating PDGF AA were highest in cases with hypoplastic left heart syndrome (HLHS) (mean 8.78 +/- 1.54 pg/ml). In this study, increased mid-pregnancy maternal serum levels of PDGF AA were associated with CCHDs in offspring. The highest PDGF AA levels were found in mothers of fetuses with HLHS. These findings may be useful in screening for CCHDs and offer insight into their association with nuchal translucency.

Ventricular fibrogenesis activity assessed by serum levels of procollagen type III N-terminal amino peptide during the staged Fontan procedure.

OBJECTIVE: We tested the hypotheses that volume overload and cyanosis observed in the pre-Fontan single ventricular circulation are associated with increased ventricular fibrogenesis, that the Fontan procedure helps to reduce fibrogenesis, and that persistently increased fibrogenesis in the Fontan ventricle is associated with ventricular diastolic dysfunction. METHODS: Levels of serum amino-terminal procollagen type III, a marker of tissue fibrogenesis, were measured in 172 patients with single ventricle circulation and 149 controls. Patients were divided into 3 groups according to surgical stage: 59 patients after Blalock-Taussig shunt or pulmonary banding, 60 patients after Glenn surgery (Glenn group), and 53 patients after Fontan surgery (Fontan group). RESULTS: Serum amino-terminal procollagen type III levels were significantly higher among the 3 single ventricle groups than among control patients, but decreased with each surgical stage (0.604, 0.176, 0.143, and 0.073 U/mL, for Blalock-Taussig shunt or pulmonary banding, Glenn, Fontan, and controls, respectively). Severity of volume load and cyanosis were independent determinants of increased amino-terminal procollagen type III levels in patients before Fontan surgery, and persistently increased amino-terminal procollagen type III after Fontan surgery was associated with ventricular diastolic stiffening (r = 0.494, P = .009). Data also indicated close associations between amino-terminal procollagen type III levels and activation of the renin-angiotensin-aldosterone system, suggesting potential involvement of this hormonal system in the increased fibrogenesis after Fontan surgery. CONCLUSIONS: These results suggest that serum amino-terminal procollagen type III may provide important diagnostic information on myocardial fibrosis in patients with single ventricle circulation and raise the possibility that ventricular fibrogenesis may be a potential therapeutic target in this population.

Cardiopulmonary Bypass Increases Plasma Glial Fibrillary Acidic Protein Only in First Stage Palliation of Hypoplastic Left Heart Syndrome.

BACKGROUND: Univentricular congenital heart defects require open-heart surgery soon after birth, and are associated with risk of brain injury and poor neurologic outcome. METHODS: This is a prospective, observational study on children undergoing cardiac surgery. Plasma glial fibrillary acidic protein (GFAP), as an early marker of brain injury, was measured by ELISA at the end of anaesthesia induction, initiation of cardiopulmonary bypass (CPB), the end of cooling, the end of rewarming, the end of CPB, and after protamine administration. We recorded clinical and surgical parameters to assess which CPB phase and clinical parameters were associated with a GFAP increase. RESULTS: We studied 13 children less than 50 months of age: 8 underwent Norwood or Damus-Kaye-Stansel palliation (group 1) and 5 underwent Fontan procedure (group 2). A GFAP increase was only observed in group 1, with the highest median value at the end of rewarming. No quantifiable levels of GFAP were measured at pre-bypass and the start of CPB stages in all patients. End of cooling and CPB-end GFAP, GFAP maximum value, and GFAP area under the curve all correlated with the CPB time spent at a cerebral regional saturation < 45% (P = 0.021, 0.028, 0.007, 0.021, respectively). CONCLUSIONS: Children with univentricular heart defects exhibit a CPB plasma-GFAP increase only after stage 1 palliation. The maximum GFAP increase occurred at the end of rewarming. Further studies are needed to identify which clinical or surgical parameter(s) could reflect a GFAP increase during surgery for congenital heart defects, and whether GFAP levels correlate with the neurologic outcome.

Association of Interstage Home Monitoring With Mortality, Readmissions, and Weight Gain: A Multicenter Study from the National Pediatric Cardiology Quality Improvement Collaborative.

BACKGROUND: Daily home monitoring of oxygen saturation and weight has been reported to improve outcomes for patients with single-ventricle heart disease during the period between stage I palliation and stage II palliation. However, these studies have been limited to single institutions and used historical control subjects. Our objective was to determine the association of various interstage home monitoring strategies with outcomes using a multicenter cohort with contemporary control subjects. METHODS AND RESULTS: We performed a retrospective cohort study using prospectively collected data from the National Pediatric Cardiology Quality Improvement Collaborative from 2008 to 2012. We compared interstage mortality, unscheduled readmissions, and change in weight-for-age Z score for various home monitoring strategies of oxygen saturation (n=494) or weight (n=472), adjusting for sex, syndrome, tricuspid regurgitation, arch obstruction, and shunt type. Overall interstage mortality was 8.1%, and 47% had ≥1 unscheduled readmission. We did not find any associations of home oxygen saturation or weight monitoring with mortality or readmission. Although there was no difference in weight-for-age Z score for daily (0.33±0.12) versus weekly (0.34±0.18, P=0.98) weight monitoring, daily home weight monitoring was superior to no home weight monitoring (-0.15±0.18; P<0.01). CONCLUSIONS: Home weight monitoring is associated with improved weight gain during the interstage period, but we did not find any benefits in other clinical outcomes for either home oxygen saturation monitoring or home weight monitoring.

Umbilical neutrophil gelatinase-associated lipocalin level as an early predictor of acute kidney injury in neonates with hypoplastic left heart syndrome.

Acute kidney injury (AKI) is a primarily described complication after unbalanced systemic perfusion in neonates with congenital heart defects, including hypoplastic left heart syndrome (HLHS). The aim of the study was to compare the umbilical NGAL concentrations between neonates born with HLHS and healthy infants, as well as to analyze whether the determination of NGAL level could predict AKI in neonates with prenatally diagnosed HLHS. Twenty-one neonates with prenatally diagnosed HLHS were enrolled as study group and 30 healthy neonates served as controls. Perinatal characteristics and postnatal parameters were extracted from the hospital neonatal database. In umbilical cord blood, we determined plasma NGAL concentrations, acid base balance, and lactate and creatinine levels. In neonates with HLHS, complications (respiratory insufficiency, circulatory failure, NEC, IVH, and AKI) were recorded until the day of cardiosurgery. We observed in neonates with HLHS higher umbilical NGAL levels compared to controls. Among 8 neonates with HLHS and diagnosed AKI stage 1, we observed elevated NGAL levels in comparison to those newborns without AKI. Umbilical NGAL could predict, with high sensitivity and specificity, AKI development in study neonates. We suggest that the umbilical blood NGAL concentration may be an early marker to predict AKI in neonates with HLHS.

Neonatal decompensation before surgery in hypoplastic left heart syndrome: a case control study.

OBJECTIVE: Prior to Norwood 1 surgery, neonates with hypoplastic left heart syndrome (HLHS) are at risk of decompensation from systemic underperfusion secondary to pulmonary overcirculation. We examined whether preoperative temporal profiles of physiological and laboratory variables differed between neonates who did and did not decompensate preoperatively. DESIGN: Case control study. SETTING: Paediatric Intensive Care Unit, 2002-2013. PATIENTS: Eighty-five neonates with HLHS, matched by birth weight and admission date. MEASUREMENTS: Decompensation was defined as the need for emergency intubation and ventilation due to clinically diagnosed impaired systemic oxygen delivery. The end point was time of decompensation (cases, n=33) or discharge for surgery (controls, n=52). Variable trajectories were modelled non-linearly using generalised estimating equations. RESULTS: Decompensation occurred on median (IQR) day 3 (2-4) of life in cases, with surgery occurring on day 4 (3-7) in controls. Oxygen saturation and blood pressure trajectories were identical between groups (p>0.2). Heart and respiratory rates increased with time overall, but significantly faster in cases than controls; by an average of 4.0 bpm/day versus 1.4 bpm/day (p=0.002) and 5.3 respirations/minute/day versus 1.5 respirations/minute/day, respectively, (p=0.003). Although metabolic blood gas components began to decline subtly 24 h before clinical decompensation, they remained in the normal range for much of this period. CONCLUSIONS: Heart and respiratory rates, and metabolic acid base trajectories show subtle differences prior to decompensation in neonates with HLHS. These findings highlight the importance of evaluating rates of change rather than absolute values of physiological and laboratory variables.

Troponin I levels in extracorporeal membrane oxygenation following congenital heart surgery.

BACKGROUND: Correlating postcardiotomy extracorporeal membrane oxygenation (ECMO) troponin I (TnI) levels and outcomes. METHODS: Between January 2006 and August 2010, 34 patients needed postcardiotomy ECMO for low cardiac output. Bailout ECMO was required either after unsuccessful weaning from bypass (n = 17, 50%), postoperatively from prolonged hemodynamic failure (n = 8, 23.5%), or following resuscitation (n = 9, 26.5%). The TnI levels were measured following surgery or resuscitation during 10 days and compared between survivors (group I) and non-survivors (group II). RESULTS: Median support duration was seven days (range: 0-31). Surgery involving hypoplastic aortic arch repair (Norwood palliation; n = 7, 20.6%, or biventricular repair; n = 11, 32.4%) led to most ECMO runs. Successful weaning from ECMO and hospital survival were 76.5% and 50%, respectively. In group I, peak TnI levels were reached by 24 hours postoperatively, comparable to levels in group II (36 ± 34 vs 49 ± 38 ng/mL; P = .98). However, in group II, TnI levels formed a plateau by the second postoperative day, whereas group I showed a steep decline in TnI levels, suggesting myocardial recovery (P = .028). All patients (n = 4) who reached or maintained peak TnI levels at 48 hours died. On days 8, 9 and 10, TnI levels were significantly higher in group II (P = .024, .019, and .013, respectively). CONCLUSIONS: Postcardiotomy ECMO was most commonly required after aortic arch repair. In the absence of ongoing myocardial insult due to ECMO hardware issues, coronary insufficiency or residual lesions, plateau TnI levels at 48 hours may seem to indicate an unfavorable outcome due to irreversible myocardial damage.

Serum cortisol and early postoperative outcome after stage-1 palliation for hypoplastic left heart syndrome.

OBJECTIVES: The postoperative cortisol profile and its association with early outcomes are poorly understood in neonates undergoing surgery for complex congenital heart disease. We investigated the postoperative profile of cortisol and its relationship with the clinical course in a cohort of newborns after stage-1 palliation for hypoplastic left heart syndrome. DESIGN: Prospective observational study. SETTING: Pediatric cardiovascular ICU at a tertiary children's hospital. SUBJECTS: Twenty-three neonates after stage-1 palliation for hypoplastic left heart syndrome between 2009 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three serial measurements of total serum cortisol after surgery. The first measurement was taken immediately after surgery and the second and third-on the first and second postoperative mornings. The median weight of the infants was 3.0 kg (2.7-3.4 kg), and the age at surgery was 7 days (6-9 d). The median (25th-75th percentile) cortisol levels at admission, day 1, and day 2 were 96.2 µg/dL (51.1-112 µg/dL), 17.3 µg/dL (9.7-25.1 µg/dL), and 10 µg/dL (6.5-17 µg/dL), respectively (p < 0.0001 between admission and day 1). Higher cortisol was associated with greater morbidity, including the need for preoperative ventilation, increased total duration of ventilation, duration of inotropic support, and hospital length of stay. CONCLUSIONS: Cortisol levels fell significantly over the first 24 hours after stage-1 palliation for hypoplastic left heart syndrome. A higher postoperative cortisol was associated with increased postoperative morbidity, which warrants further investigation.

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.

Cardiac troponin I, cardiac troponin-specific autoantibodies and natriuretic peptides in children with hypoplastic left heart syndrome.

OBJECTIVES: To evaluate serum levels of cardiac troponin I (cTnI), autoantibodies against cardiac troponin (cTnAAbs) and natriuretic peptides during the treatment protocol in children with hypoplastic left heart syndrome (HLHS). METHODS: In a prospective study, we had 18 consecutive children with HLHS, for whom serum samples were analysed before the Norwood operation, before the bidirectional Glenn (BDG) operation, at the age of one year and before total cavo-pulmonary connection (TCPC). In addition, we performed a cross-sectional study in 22 children examined before TCPC. Controls comprised 34 healthy children. RESULTS: In the prospective study, troponin I was positive in eight children before the Norwood operation. At the next follow-up, six children were positive. Thereafter, in all samples, cTnI was negative. Serum levels of natriuretic peptides decreased during the treatment protocol but remained higher than in controls throughout the study. In the cross-sectional study, cTnI levels were negative, but levels of natriuretic peptides were higher than in controls. Levels of cTnI and natriuretic peptides showed no correlation with oxygen saturation or haemoglobin concentration. Autoantibodies against cardiac troponin appeared in one patient but not in the control children. CONCLUSIONS: Cardiac TnI release is common before Norwood and BDG operations; then during the treatment protocol for HLHS, cTnI release resolves and serum levels of natriuretic peptides decrease. This may reflect a reduction of volume overload of the right ventricle during the surgical programme.

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

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

Mitochondrial DNA depletion syndrome-an unusual reason for interstage attrition after the modified stage 1 Norwood operation.

We describe a patient with a variant of the hypoplastic left heart syndrome who died 16 weeks after a modified stage 1 Norwood from a mitochondrial DNA depletion syndrome.

The importance of blood lactate clearance as a predictor of early mortality following the modified Norwood procedure.

OBJECTIVE: Optimisation of Norwood physiology, with focus on systemic perfusion, has beneficial effects on haemodynamic stability and perioperative mortality following the Norwood procedure for hypoplastic left heart syndrome. Early identification of high-risk patients during the postoperative phase might allow for institution of alternative management strategies with the possibility of avoiding poor outcome. Several studies have suggested that arterial blood lactate level, as an index of systemic perfusion and oxygen delivery, can to some extent predict mortality following paediatric cardiac surgery, though these studies have included heterogeneous groups of patients with only few Norwood patients. We sought to determine whether the blood lactate profile could be used to derive a simple, clinically applicable decision algorithm to direct therapy in a pre-emptive manner and perhaps identify patients for elective extracorporeal life support following the Norwood procedure. METHODS: We retrospectively analysed all patients at our institution who had undergone modified Norwood procedures between March 2002 and May 2008. All patients had received right ventricle-pulmonary artery conduits. Patients with systemic-pulmonary shunts were excluded. Outcome measures included 7-day and 30-day mortality. Serial arterial blood lactate measurements were taken in all patients for at least 72h. Conditional inference tree modelling was used to determine the discriminatory value of the lactate profile and other pre- and intra-operative risk factors in terms of selecting survivors. RESULTS: As many as 221 patients were included. The 7-day ICU mortality was 26/219 (11.8%) with total 30-day mortality of 35/219 (15.8%). There were 21 interstage deaths. Mortality modelling demonstrated that an inability to clear blood lactate levels to <6.76mmoll(-1) within the first 24h was highly discriminatory in terms of predicting death within the first 30 days. A total of 11 out of 12 patients in this group died. Other risk factors examined, including weight, ascending aorta size, cardiopulmonary bypass and ischaemic times, were not as predictive in our model. CONCLUSION: We have identified minimum blood lactate level within the first 24h after the Sano-Norwood procedure as a highly discriminatory predictor of perioperative mortality. These patients might benefit from elective institution of early mechanical circulatory support.

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.

The effectiveness of high-flow regional cerebral perfusion in Norwood stage I palliation.

OBJECTIVE: Regional cerebral perfusion (RCP) has been shown to provide cerebral circulatory support during Norwood procedure. In our institution, high-flow RCP (HFRCP) from the right innominate artery has been induced to keep sufficient cerebral and somatic oxygen delivery via collateral vessels. We studied the effectiveness of HFRCP to regional cerebral and somatic tissue oxygenation in Norwood stage I palliation. METHODS: Seventeen patients, who underwent the Norwood procedure, were separated into two groups: group C (n=6) using low-flow RCP and group H (n=11) using HFRCP (mean flow: 54 vs 92mlkg(-1)min(-1), P<0.0001). The mean duration of RCP was 64±10min (range, 49-86min) under the moderate hypothermia. Chlorpromazine (3.0mgkg(-1)) was given to group H patients before and during RCP to increase RCP flow. The mean radial arterial pressure was kept <50mmHg during RCP. To clarify the effectiveness of HFRCP for cerebral and somatic tissue oxygenation, cerebral regional oxygen saturation (rSO(2)) and systemic venous oxygenation (SvO(2)) during RCP were compared between the two groups. Changes in the lactate level before and after RCP, and changes in the blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and creatinine kinase (CK) levels before and after surgery, were also compared between the groups. RESULTS: Mean rSO(2) was 82.9±9.0% in group H and 65.9±10.7% in group C (P<0.05). Mean SvO(2) during RCP was 98.2±4.3% in group H and 85.4±9.7% in group C (P<0.01). During RCP, lactate concentration significantly increased in group C compared with that in group H (P<0.001). After surgery, the LDH and CK levels significantly increased in group C compared with that in group H (P<0.05). CONCLUSIONS: Our study revealed that HFRCP preserved sufficient cerebral and somatic tissue oxygenation during the Norwood procedure. The reduction of vascular resistance of collateral vessels increased both cerebral and somatic blood flow, resulting in improved tissue oxygen delivery.