Publications

Scholarly Journals--Published

• Lynch JM, Buckley EM, Schwab PJ, McCarthy AL, Winters ME, Busch DR, Xiao R, Goff DA, Nicolson SC, Montenegro LM, Fuller S, Gaynor JW, Spray TL, Yodh AG, Naim MY, Licht DJ. Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome.J Thorac Cardiovasc Surg.148(5):2181-8, 2014.  OBJECTIVE:Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown.METHODS:Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression.RESULTS:A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P=.0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P=.03 and P=.05, respectively) and greater oxygen extraction fraction (P=.05 for both).CONCLUSIONS:A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury. (11/2014)
• Goff DA, Shera D, Tang S, Lavin, NA, Durning S, Nicolson S.C., Montenegro L, Wernovsky G, Rome J, Gaynor J.W., Spray T.L., Zimmerman R.J., Licht D.J. Preoperative risk factors for periventricular leukomalacia in hypoplastic left heart syndrome. JTCVS. 147(4):1312-18, 2014. BACKGROUND: Preoperative brain injury is common in neonates with complex congenital heart disease. Increasing evidence suggests a complex interaction of prenatal and postnatal risk factors for development of brain white matter injury, called periventricular leukomalacia (PVL), in neonates with complex congenital heart disease. To date, there remains a limited understanding of the risk factors contributing to preoperative PVL in hypoplastic left heart syndrome (HLHS).METHODS:Neonates with HLHS or HLHS variants from 3 prospective magnetic resonance imaging studies (2003-2010) were selected for this cohort. Preoperative brain magnetic resonance imaging was performed the morning of the surgery. Stepwise multilogistic regression of patient characteristics, mode of delivery (cesarean section vs vaginal), time of diagnosis (prenatal vs postnatal), HLHS subtypes, brain total maturation score, time to surgery, individual averaged daily preoperative blood gases, and complete blood cell count values was used to determine significant associations.RESULTS:A total of 57 neonates with HLHS were born at 38.7 ± 2.3 weeks; 86% (49/57) had a prenatal diagnosis, with 31% (18/57) delivered by cesarean section. HLHS with aortic atresia (AA) was common in this cohort, 71% (41/57). Preoperative PVL was identified in 19% (11/57). Male patients with AA (P = .004) were at higher risk for PVL. Lower total brain maturation score was also identified as a strong predictor for preoperative PVL (P = .005).CONCLUSIONS:In neonates with HLHS, nonmodifiable patient-related factors, including male sex with AA (lack of antegrade blood flow) and lower total brain maturation score, placed neonates at the greatest risk for preoperative white matter injury. (04/2014) (link)
• Oliver E R, Coleman B G, Goff D A, Horii S C, Howell L J, . . . Johnson M P. (2013). Twin Reversed Arterial Perfusion Sequence A New Method of Parabiotic Twin Mass Estimation Correlated With Pump Twin Compromise. Journal of Ultrasound in Medicine, 32(12), 2115-2123. Objectives-The purpose of this study was to test the hypothesis that using the formula of a prolate ellipsoid to estimate parabiotic twin mass correlates better with findings of pump twin compromise than using the sonographic method of Moore et al (Am J Obstet Gynecol 1990; 163:907-912). Methods-A 10-year retrospective review was performed to identify all cases of the suspected twin reversed arterial perfusion (TRAP) sequence. Parabiotic twin mass was estimated by summing body and extremity volumes calculated using the prolate ellipsoid formula (width x height x length x 0.523). Parabiotic twin mass was also estimated using the sonographic Moore method [1.21 x length(2) - (1.66 x length)]. Parabiotic twin mass estimated by both methods was correlated with sonographic findings associated with increased risk of pump twin compromise. Results-Fifty-nine pregnancies complicated by TRAP were identified. Using the prolate ellipsoid formula, the parabiotic twin mean sizes +/- SD (as a percentage of pump twin weight) were 103.0% +/- 52.0% and 56.9% +/- 44.3% in cases with and without pump twin compromise (P = .0005), respectively. Using the sonographic Moore method, the mean parabiotic twin sizes were 122.9% +/- 54.3% and 99.6% +/- 62.8% in cases with and without pump twin compromise (P = .14). The median estimated masses of the parabiotic twin were 197 219 g using the prolate ellipsoid formula and 310 212 g using the sonographic Moore method (P = .0001). A parabiotic twin size greater than 70% of the pump twin correlated with findings associated with increased risk of pump twin compromise when using the prolate ellipsoid formula (P = .002) but not the sonographic Moore method (P = .09). Conclusions-Sonographic findings associated with increased risk of pump twin compromise correlate better with prolate ellipsoid estimates of parabiotic twin mass. The median estimated mass of the parabiotic twin was statistically larger when calculated by the sonographic Moore method than by the prolate ellipsoid formula. (12/2013) (link)
• Buckley E M, Naim M Y, Lynch J M, Goff D A, Schwab P J, . . . Licht D J. (2013). Sodium bicarbonate causes dose-dependent increases in cerebral blood flow in infants and children with single-ventricle physiology. Pediatric Research, 73(5), 668-673. BACKGROUND: Sodium bicarbonate (NaHCO3) is a common treatment for metabolic acidemia; however, little definitive information exists regarding its treatment efficacy and cerebral hemodynamic effects. This pilot observational study quantifies relative changes in cerebral blood flow (Delta rCBF) and oxy- and deoxyhemoglobin concentrations (Delta HbO(2) and Delta Hb) due to bolus administration of NaHCO3 in patients with mild base deficits. METHODS: Infants and children with hypoplastic left heart syndrome (HLHS) were enrolled before cardiac surgery. NaHCO3 was given as needed for treatment of base deficit. Diffuse optical spectroscopies were used for 15 min postinjection to noninvasively monitor Delta Hb, Delta HbO(2), and Delta rCBF relative to baseline before NaHCO3 administration. RESULTS: Twenty-two anesthetized and mechanically ventilated patients with HLHS (aged 1 d to 4 y) received a median (interquartile range) dose of 1.1 (0.8, 1.8) mEq/kg NaHCO3 administered intravenously over 10-20 s to treat a median (interquartile range) base deficit of -4 (-6, 3) mEq/l. NaHCO3 caused significant dose-dependent increases in Delta rCBF; however, population-averaged Delta Hb and Delta HbO(2) as compared with those of controls were not significant. CONCLUSIONS: Dose-dependent increases in cerebral blood flow (CBF) caused by bolus administration of NaHCO3 are an important consideration in vulnerable populations wherein risk of rapid CBF fluctuations does not outweigh the benefit of treating a base deficit. (05/2013) (link)
• Buckley E M, Lynch J M, Goff D A, Schwab P J, Baker W B, . . . Licht D J. (2013). Early postoperative changes in cerebral oxygen metabolism following neonatal cardiac surgery: Effects of surgical duration. Journal of Thoracic and Cardiovascular Surgery, 145(1), 196-+. Objective: The early postoperative period following neonatal cardiac surgery is a time of increased risk for brain injury, yet the mechanisms underlying this risk are unknown. To understand these risks more completely, we quantified changes in postoperative cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood flow (CBF) compared with preoperative levels by using non-invasive optical modalities. Methods: Diffuse optical spectroscopy and diffuse correlation spectroscopy were used concurrently to derive cerebral blood flow and oxygen utilization postoperatively for 12 hours. Relative changes in CMRO2, OEF, and CBF were quantified with reference to preoperative data. A mixed-effect model was used to investigate the influence of total support time and deep hypothermic circulatory arrest duration on relative changes in CMRO2, OEF, and CBF. Results: Relative changes in CMRO2, OEF, and CBF were assessed in 36 patients, 21 with single-ventricle defects and 15 with 2-ventricle defects. Among patients with single-ventricle lesions, deep hypothermic circulatory arrest duration did not affect relative changes in CMRO2, CBF, or OEF (P > .05). Among 2-ventricle patients, total support time was not a significant predictor of relative changes in CMRO2 or CBF (P > .05), although longer total support time was associated significantly with greater increases in relative change of postoperative OEF (P = .008). Conclusions: Noninvasive diffuse optical techniques were used to quantify postoperative relative changes in CMRO2, CBF, and OEF for the first time in this observational pilot study. Pilot data suggest that surgical duration does not account for observed variability in the relative change in CMRO2, and that more comprehensive clinical studies using the new technology are feasible and warranted to elucidate these issues further. (J Thorac Cardiovasc Surg 2013;145:196-205) (01/2013) (link)