Effects of circulatory arrest and cardiopulmonary bypass on cerebral autoregulation in neonatal swine

Jonah A Padawer-Curry,Alexander L Schmidt,Brian R White,Tami Rosenthal ,Kellie L Schiavo,Arjun G Yodh,Jake Breimann ,Christopher E Mascio,Daniel J Licht,Constantine Mavroudis ,David R Busch,Brandon C Shade ,Tiffany Ko ,Kristen Andersen ,Vincent C Morano,Lindsay Volk ,Timothy W Boorady,Todd J Kilbaugh,Kobina Mensah-Brown ,Richard W Melchior ,Jharna Jahnavi,Wesley B Baker

doi:10.1038/s41390-021-01525-3

Abstract

BackgroundCerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. In this study, alterations of cerebral autoregulation were assessed in a neonatal swine model probing four perfusion strategies.MethodsNeonatal swine (n = 25) were randomized to continuous deep hypothermic cardiopulmonary bypass (DH-CPB, n = 7), deep hypothermic circulatory arrest (DHCA, n = 7), selective cerebral perfusion (SCP, n = 7) at deep hypothermia, or normothermic cardiopulmonary bypass (control, n = 4). The correlation coefficient (LDx) between laser Doppler measurements of CBF and mean arterial blood pressure was computed at initiation and conclusion of CPB. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements.ResultsCerebral autoregulation became more impaired (LDx increased) in piglets that underwent DH-CPB (initial LDx: median 0.15, IQR [0.03, 0.26]; final: 0.45, [0.27, 0.74]; p = 0.02). LDx was not altered in those undergoing DHCA (p > 0.99) or SCP (p = 0.13). These differences were not explained by other risk factors.ConclusionsIn a validated swine model of cardiac surgery, DH-CPB had a significant effect on cerebral autoregulation, whereas DHCA and SCP did not.ImpactApproximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays. This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB.We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery.Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.

Highlights

The prevalence of neurodevelopmental anomalies in neonates who underwent cardiac surgery with cardiopulmonary bypass (CPB) exceeds 30%,3,5 but the extent to which perioperative and intraoperative factors contribute to neurological injury is unknown, because mechanisms of neurologic injury during cardiac surgery are multifactorial and incompletely understood.[6,7]
Twenty-five piglets were included in the study, with seven randomized to each experimental condition (DH-CPB, selective cerebral perfusion (SCP), and deep hypothermic circulatory arrest (DHCA)) and four randomized to the control group
The experimental groups did not differ in any clinical variables (Table 1), except for (a) SCP had a longer time on bypass prior to the initial LDx assessment than DH-CPB (44 ± 15 min compared to 25 ± 8 min; p = 0.01); (b) SCP had a lower cumulative dexmedetomidine dose than DHCA

Summary

BACKGROUND

Cerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements. CONCLUSIONS: In a validated swine model of cardiac surgery, DH-CPB had a significant effect on cerebral autoregulation, whereas DHCA and SCP did not. ● Approximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB. ● We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery. ● Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP

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RESULTS

DISCUSSION