Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high flow bypass and cerebral oxygenation monitoring
The Journal of Thoracic and Cardiovascular Surgery 2010; 139(3): 543-56
Reviewed by Kelly Chilson, MD
In pediatric congenital heart surgery, the outcomes focus is shifting from survival to neurodevelopmental outcome. This prospective, observational study was conducted to determine the incidence and severity of new brain injury on MRI with the use of high flow cardiopulmonary bypass (CPB) and to determine if brain injury was significantly associated with patient or procedural factors. The hypothesis stated that patients with immature brains would be more likely to have pre- and post-operative brain injury. This hypothesis was tested by comparing preoperative MRI scans with those acquired in the immediately (7-10days) post op and a third scan acquired at the age of 3-6 months immediately prior to the second stage surgery. Brain developmental maturity was measured using modified Child’s scoring system by a pediatric neuro-radiologist, blinded to the cardiac diagnosis and the nature of the surgery. The incidence of new intraparenchymal lesions including white matter injury, infarction and hemorrhage, was the primary outcome.
Data was analyzed comparing single and two ventricle groups. Linear regression analysis using block entry model was used to determine the association of clinical variables with brain injury and late death. The study was powered to detect a 40% increase in the MRI findings.
Sixty eight patients from Texas Children’s Hospital were recruited for this study. Children younger than thirty days of age who underwent single or biventricle repair with the use of hypothermic (<30 degrees) CPB were included in the study. Patients less than 35 weeks estimated gestational age at birth, weight less than two kilograms, identifiable dysmorphic syndrome, and preoperative cardiac arrest for greater than three minutes were excluded from the study.
A standard anesthetic technique including high dose Fentanyl, midazolam, and isoflurane, along with neuromuscular blockade, was used in all patients. The CPB flows of 150 ml/kg/min with target mean arterial blood pressure (MAP) of 30-35 mmHg was used in all patients. CPB management strategies included pH stat arterial blood gas management, cooling for greater than 20 minutes and continuous ultrafiltration. Hematocrit was maintained between 30-35 during the cooling period. During ACP, bypass flows were adjusted to keep the transcutaneous Doppler measurements within 10% of baseline values measured during full CPB. Near infrared spectroscopy monitoring was used during the pre, intra-op and postop period. Interventions to treat NIRS values less than 50 were initiated according to a pre-determined protocol.
The overall incidence of new white matter injury (WMI), infarction, or hemorrhage was 36%. The total maturity score (TMS) and incidence of preoperative MRI was similar in the single and two ventricle patients. This tested hypothesis established association between the low TMS (increasing brain immaturity) and increased severity of post-operative brain injury, preoperative white matter injury, and post-operative white matter injury. Additionally, the study demonstrated an association between sustained low diastolic blood pressure and new brain injury. Surprisingly, this study was unable to find association between low rSO2 values and post-operative MRI brain injury. Of note, 45 patients have received the third MRI, 58% children had complete or partial resolution of previous findings. However, 27% children had additional findings not seen in the previous MRI scans.
This study shows that brain immaturity in neonates with congenital heart disease is associated with pre and post-operative brain injury. Also, this study suggests that a greater proportion of patients with congenital heart disease have brain immaturity than in a normal population. This finding is in agreement with a recent study by Licht et al that reported structurally immature brains in a population of patients with hypoplastic left heart syndrome and transposition of the great arteries.
The incidence of new brain injury in the current study is much lower (36%) than reported in the previous studies by Mahle and Dent (67 and 73%). However, a study by McQuillen et al, using bypass strategies similar to the current study, also found a 36% incidence of new brain injury. In the absence of a control group, it is not possible to attribute this improvement to the use of the bypass management.
TMS is a semi-quantitative scale that measures brain development maturity index for neonates between 23 and 41 weeks. Many other confounding variables including genotypic variation, inflammatory response to the surgery and maternal infections etc. may also contribute to brain injury. Also, the small sample size makes it difficult to make any conclusions about the association between brain immaturity and late death in the single ventricle group.
This study achieves the goal of establishing clear association between brain immaturity in children with complex congenital heart disease and postoperative risk of brain injury. Further studies would be necessary to delineate mechanisms of the intra-operative injury. There are many unanswered questions that need to be addressed as we further define the perioperative insults that may contribute to neurologic disability. Will it be necessary to have brain MRI results on all neonatal cardiac patients? What will we do with that information? Can we or should we delay surgery awaiting brain maturation? And once in the operating room, what cardiopulmonary bypass technique and monitoring strategies will produce the minimal amount of injury? Long term follow up will be required to correlate MRI findings will actual patient neuro-developmental abnormalities.
References:
- Licht DJ, Shera DM, Clancy RR, Wernovsky G, Montenegro LM, Nicolson SC, et al. Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg. 2009;137:529-36.
- Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, et al. An MRI study of neurological injury before and after congenital heary surgery. Circulation. 2002;106(suppl I):I-109-14.
- Dent CL, Spaeth JP, Jones BV, Schwartz SM, Glauser TA, Hallinan B, et al. Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion. J Throrac Cardiovasc Surg. 2006;131:190-7.
- McQuillen PS, Barkovich AJ, Hamrick SE, Perez M, Ward P, Glidden DV, etal. Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke. 2007;38:736-41.