Objective. To identify pre- and intraoperative variables associated with postoperative acute neurologic events (ANEs), including seizures and coma, in newborn survivors of congenital heart surgery undergoing deep hypothermic circulatory arrest (DHCA), and to risk-stratify this population on the basis of preoperative risk variables for the purpose of designing future neuroprotection trials.
Methods. Survivors of newborn heart surgery who were enrolled in a neuroprotection trial provided a comprehensive database for the evaluation of pre- and intraoperative variables that influence the postoperative occurrence of ANEs (seizures or coma). Patients with hypoplastic heart syndrome were excluded. After characterization of the study population, stepwise logistic regression, combined with clinical judgment, was used to identify variables that were most likely to be associated with an increased risk of seizures in the study sample and that were most likely to be generalized to other populations.
Results. Data were available on 164 nonhypoplastic left heart syndrome survivors who underwent newborn heart surgery using DHCA. ANEs occurred in 31 (18.9%) including “seizures alone” (n = 28), “coma alone” (n = 2) or “seizures and coma” (n = 1). A preoperative risk model was constructed demonstrating that infants with a genetic condition and aortic arch obstruction had a 47.8% risk of ANEs compared with all other remaining infants, who had a 9.9% risk. It was also found that prolonged DHCA time (60 minutes) can be a significant risk for infants who have a preexisting genetic condition; however, infants who have genetic conditions and do not undergo prolonged DHCA time or have an aortic arch obstruction are not at increased risk of ANEs.
Conclusions. This study provides new information about the occurrence of ANEs after newborn heart surgery. Seizures or coma, which appeared in approximately 19% of all non–hypoplastic left heart syndrome survivors, were not random events but were significantly associated with specific types of congenital heart disease, the presence of genetic conditions, and prolonged DHCA time. The 3 identified variables permitted individual cases to be assigned to low-, intermediate-, or high-risk categories. Because neonatal seizures are a good surrogate marker of long-term neurologic outcome, these models provide useful information to stratify individual patients for risk of seizures in future neuroprotection trials.
After newborn heart surgery, some infants demonstrate acute neurologic events (ANEs), including seizures or coma, that signify neurologic dysfunction and often brain injury. Furthermore, seizures may serve as an ideal early “surrogate” endpoint in neuroprotection trials. Although the occurrence of postoperative seizures and coma is well known, there is limited understanding of the pre- and intraoperative risk factors that may influence their occurrence in infants who undergo various types of congenital heart disease (CHD) surgery. The investigation by Newburger et al of postoperative seizures after repair of transposition of the great arteries (TGA) identified higher risk infants as those 1) with a ventricular septal defect, 2) undergoing deep hypothermic circulatory arrest (DHCA), compared with low-flow cardiopulmonary bypass (CPB) having longer duration of DHCA. It is unknown, however, whether the risk factors are consistent across all forms of CHD requiring neonatal surgical repair using DHCA.
The results of the Children’s Hospital of Philadelphia allopurinol neurocardiac protection trial were reported using 2 strata of infants who underwent newborn heart surgery using DHCA: 1) hypoplastic left heart syndrome (HLHS) and 2) all other forms of CHD (non-HLHS). Allopurinol was not associated with improved survival in either strata, but in the survivors of the HLHS strata, allopurinol administration was associated with a statistically significant reduction in the occurrence of “seizures” and “cardiac events.” In the non-HLHS strata, no allopurinol-related reduction in morbidity was observed. Consequently, the surviving non-HLHS infants in that trial allow for an evaluation of pre- and intraoperative factors that are associated with ANEs. HLHS survivors were excluded from this analysis because, as a group, they were significantly different from the non-HLHS group with respect to their concurrent genetic conditions and their response to the neuroprotection agent. The purpose of this investigation was to identify the pre- and intraoperative factors that are associated with postoperative ANEs in an anatomically diverse population of survivors of newborn heart surgery using DHCA. Once identified, these factors could be used to risk-stratify infants in future newborn heart surgery neuroprotection trials.
This is an excerpt of a study published by the AAP. To read the study in its entirety, click here.