Brain Autoregulation Research Study

Bradley Marino

Status: Not yet enrolling

Conditions: Hypotension During Surgery; Hypotension Postprocedural

Treatments: Device: Surgery with Active MAP Management; Other: Surgery without Active MAP Management

Study type: Interventional

Funder types: Other

Identifiers

NCT07221721

IRB 22-1348

Details and patient eligibility

About

Randomized, multi-site, study assessing the feasibility of lower limit of autoregulation targeted mean arterial pressure (MAP) vs. standard MAP management in neonates undergoing cardiac surgery with cardiopulmonary bypass. After eligibility screening and consent, subjects will be randomized to either the intervention (study) or control group.

Full description

Congenital heart disease (CHD) is the most common birth defect.1 Surgery to treat CHD is complicated by white matter injury (WMI) on brain magnetic resonance imaging (MRI) and neurodevelopmental (ND) deficits in 50% to 75% of neonates after CHD surgery.2-6 Cerebral hypoperfusion is a major mechanism of brain injury during both cardiopulmonary bypass (CPB) and the perioperative period in the intensive care unit (ICU).7-10 Investigators lack diagnostic and therapeutic means to reduce cerebral hypoperfusion-associated white matter injury (WMI) and improve long-term ND outcomes.11 Our long-term goal is to use real-time measurement of the cerebral lower limit of autoregulation (LLA) to manage arterial blood pressure, reduce cerebral hypoperfusion-associated brain injury, and improve long-term ND outcomes in children at risk for brain hypoperfusion. In a prospective, single blind, randomized clinical trial (RCT) in adults undergoing cardiac surgery, investigators previously showed that targeted LLA arterial blood pressure management to maintain mean arterial pressure (MAP) above the LLA decreased the incidence of postoperative delirium by 45%.12 Our preliminary data indicate that neonates are exposed to significantly more cerebral hypotension than adult patients undergoing CPB. Our central hypothesis is that a strategy of targeting mean arterial pressure (MAP) to a level above an individual's LLA will reduce the risk for WMI and neurodevelopmental impairment in neonates undergoing congenital heart surgery. Our team has validated methodology to delineate the LLA and demonstrated the important role of cerebral autoregulation monitoring on short-term outcomes in CHD subjects who have undergone CPB.13 We can rigorously measure cerebral autoregulation in real time and the amount of cerebral hypotension (duration and magnitude) through the integration of near infrared spectroscopy (NIRS) and the arterial blood pressure.14,15 The efficacy of an LLA targeted MAP strategy to minimize WMI and improve ND outcomes can only be demonstrated by a prospective, single-blind, multi-center randomized RCT. To obtain funding for this large multi-center RCT will require the demonstration of feasibility and safety, as well as, an estimation of the sample size needed to show efficacy.

Enrollment: 130 estimated patients

Sex: All

Ages: 30 to 30 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• All neonates (<30 days of age)
• Undergoing cardiothoracic surgery with cardiopulmonary bypass

Exclusion criteria

• Less than full term (<37 weeks gestation)
• Weight < 2.50kg
• Genetic abnormality or syndrome except heterotaxy syndrome
• Major non-cardiac anomalies (e.g. congenital diaphragmatic hernia, - omphalocele, holoprosencephaly, anencephaly)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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130 participants in 2 patient groups

Intervention (Study) Group

Experimental group

Description:

Neonates undergoing cardiothoracic surgery (CT) utilizing cardiopulmonary bypass (CPB) who will have active management of their mean arterial pressure (MAP) to keep the MAP above the LLA as measured by a novel autoregulation monitoring modality.

Treatment:

Device: Surgery with Active MAP Management

Control Group

Sham Comparator group

Description:

Neonates undergoing cardiothoracic surgery (CT) utilizing cardiopulmonary bypass (CPB) who will have management of their MAP by institutional practice without guidance from an autoregulation monitoring modality.

Treatment:

Other: Surgery without Active MAP Management