The Never-Ending Quest To Improve Neurodevelopmental Outcomes After Neonatal Cardiac Surgery
Susan Nicolson, Vivian Nasr, Lindsey Loveland Baptist, James DiNardo
Original article
Hsia J, Abend NS, Gaynor JW, Chen JM, Fuller S, Maaeda K, Mavroudis CD, Nuri M, Leonard J, Ampah ST, Licht DJ, Masssey S, Naim MY. Incidence of Postoperative Seizures in Neonates Following Surgery with Regional Cerebral Perfusion and Deep Hypothermic Circulatory Arrest. JTCVS Open 4 october 2023
Long term neurodevelopmental impairment remains a significant source of morbidity in survivors of neonatal cardiac surgery. For operations facilitated by a bloodless field, the use of deep hypothermic circulatory arrest (DHCA) as a neuroprotective strategy may contribute to neurologic injury due to exposure to cerebral ischemia. Regional cerebral perfusion (RCP) was developed as an alternative to DHCA that could achieve a comparable surgical field while providing some degree of cerebral perfusion with the goal of preventing hypoxic ischemic brain injury. Data comparing neurologic outcomes in patients undergoing DHCA and RCP are conflicting resulting in practice variation, both in the use of each modality and how each is executed, among pediatric cardiac surgeons (ref 1-3).
Postoperative seizures in neonates following cardiac surgery have been linked to adverse long-term neurodevelopmental outcomes (ref 4). Given the lack of consensus regarding the optimal strategy for neuroprotection, the authors compared the incidence of postoperative EEG seizures between neonates undergoing cardiac surgery with the two methods for neuroprotection.
The primary outcome, EEG seizure occurrence, was used as a surrogate for neurologic injury. Seizures were defined as an abnormal paroxysmal EEG event different from background lasing longer than 10 seconds (less if associated with a clinical seizure).
A retrospective analysis was performed in neonates (less than corrected 44 weeks gestational age) at a single center who underwent cardiac surgery between 2012 and 2022 using either DHCA or RCP. Routine postoperative continuous electroencephalographic (cEEG) monitoring initiated within 6 hours of arrival to the intensive care unit and continued for 48 hours was implemented in 2012. For patients with multiple surgeries in the neonatal period, only the index surgery was included. Neonates undergoing DHCA were cooled to a temperature of 18 degrees C over 15-20 minutes and rewarmed over 22 minutes. For patients undergoing RCP, the flow rate was determined by the surgeon and was variable. The median RCP flow rate was 50 ml/kg/min with minimum and maximum flow rates of 25 ml/kg/min and 60 ml/kg/min respectively. Patients where RCP was used were cooled to a temperature of 18-24 degrees C at the discretion of the surgeon over 15-20 minutes. Patients were monitored with either uni or bifrontal near infrared spectroscopy (NIRS). Patients were rewarmed over 22 minutes.
Propensity-score matched analysis was used to reduce selection bias and account for differences between DHCA and RCP groups. Propensity scores were estimated using a logistic regression model in which the dependent variable was RCP and the independent variables were gestational age and STAT class.
During the 10.5 year time interval 1143 neonates underwent cardiac surgery with CPB, RCP was used in 99 (8.7%) and DHCA in 604 (53%). Ninety six percent of patients in the RCP group underwent surgery in the most recent surgical era (2019-2022). After propensity score matching, there were 99 RCP and 297 DHCA patients.
Median gestational age of the cohort was 39 weeks (IQR 38.0, 39.1). Median age at the time of surgery was 4.0 days (IQR 3.0, 6.0).
The median duration of RCP was 49 minutes (IQR 38, 68) and DHCA was 41 minutes (IQR 31, 49). Brief periods of DHCA were used in 54% (n= 53) of the RCP group with a median duration of 6 minutes (range 1-21 minutes). Intermittent reperfusion was used in 1% of the DHCA patients with a median duration of 5 minutes (range 3-7 minutes). The RCP group had significantly longer total support, CPB and aortic cross clamp times.
In the most recent era (2019-2022), the unadjusted seizure incidence was similar in neonates undergoing RCP (n =12, 12%) and DHCA (n= 64, 11%). Following propensity matching, the seizure incidence in neonates undergoing RCP (n=12, 12%) and DHCA (n=37, 12%). Patients with single ventricle physiology had a higher incidence of seizures compared to those with two ventricles. The incidence of cardiac arrest in the OR was higher in the RCP cohort (5% versus 0.3%). Survival to hospital discharge was not different between the two groups.
In this single-center study, the incidence of EEG seizures remains similar to previous years and the incorporation of RCP into the practice was not associated with a lower incidence of seizures in comparison to DHCA (Fig). The variation in RCP flow rates used and no consensus regarding optimal flow rate, may impact the negative finding in this study. A significant number of patients where RCP was used also had some period of DHCA and neonates managed with RCP had a higher incidence of intra-operative cardiac arrest. Both of these occurrences may further confound the findings.
This retrospective study has several limitations: application of EEG as late as 6 hours postop could have missed identification of early seizure activity, changes over time not accounted for by propensity score matching, vast majority of RCP patients (96%) underwent surgery in the most recent era, lack of a protocol to guide RCP flow titration, and lack of standardized neuromonitoring during RCP cases
It is not likely there would be equipoise among surgeons to conduct a study to determine whether RCP is a superior neuroprotective strategy to DHCA. However, multi-center studies are needed to determine the optimal RCP flow rate and subsequently to determine the impact, if any, of RCP on postoperative incidence of seizures in neonates and long-term neurodevelopmental outcomes.
References:
1. Kornilov IA et al., Outcomes after aortic arch reconstruction for infants: deep hypothermic circulatory arrest versus moderate hypothermia with selective antigrade cerebral perfusion. Eur J Cardiothorac Surg, 2015. 48(3): e45-50.
2. Goldberg CS et al., A randomized clinical trial of regional cerebral perfusion versus deep hypothermic circulatory arrest: outcomes for infants with function single ventricle. J Thorac Cardiovasc Surgery, 2007. 133(4) 880-887.
3. Visconti KJ et al., Regional low-flow perfusion versus circulatory arrest in neonates: one-year neurodevelopmental outcome. Ann Thorac Surg, 2010. 90(6): 1985-1984.
4. Bellinger, DC et al. Adolescents with d-transposition of the great arteries corrected with the arterial switch procedure: neuropsychological assessment and structural brain imaging. Circulation, 2011. 124(12): 1361-1369.+