Cerebral Blood Flow in Neonates During Major Cardiac Surgery. (FLOWER)

Cerebral Blood Flow in Neonates During Major Cardiac- and Non-cardiac Surgery

Rationale: During cardiac surgery, neonates are at high risk of cerebral damage: 36-78% will have new cerebral lesions after surgery. Adequate cerebral perfusion (CBF) is mandatory to prevent postoperative brain damage and neurobehavioral outcomes. For CBF, the systemic blood pressure should be managed above the brain's critical closing pressure (CrCP), and preferably above the lower limit of autoregulation (LLA), if intact.

Objective: The investigators aim to study the patient specific threshold for arterial blood pressure to maintain adequate cerebral perfusion (CBFV) in the perioperative setting and the association between perioperative abnormalities with postoperative brain damage and neurobehavioral outcomes.

Study design: In a prospective observational cohort study bilateral cerebral blood flow velocity (CBFV) measurements are performed with transcranial doppler (TCD), together with invasive arterial blood pressure (iABP) measurements in the perioperative period.

Study population: Neonates (semi-) electively scheduled for major cardiac- and non cardiac surgery.

Main study parameters/endpoints: Main study endpoint is the Critical Closing Pressure (CrCP) within and between subjects. Furthermore, we evaluate the association with new white matter injury (WMI) on the postoperative MRI.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Anticipated risks caused by TCD monitoring in neonates are considered negligible when monitoring is executed according to the BMUS guidelines and ALARA principle. Each time energy is converted from one form to another, part of it is inevitably converted to heat. Theoretically, if at all, the maximum temperature rise will happen at the skin- temporal bone side, where the monitoring probes are placed. A maximal thermal index (TI) of 0.7 is allowed, this corresponds with 0.7 o C temperature rise.

Patients might not benefit from participation in this study as the TCD measurements are only visible and available to the TCD operator, and we do not yet know how the results could possibly influence the procedure. However, in the unlikely situation where cerebral perfusion is severely compromised for a longer period of time or in case of occurrence of large air emboli, improper cannulation or cross clamping the cardiac team will be notified. Therefore, a neonate might benefit from participation.

Study Overview

• Status: Recruiting
• Conditions: Hypoperfusion in Newborn With Congenital Heart Disease
• Intervention / Treatment: Device: Critical closing pressure detection

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Sylvia van Rossum; Phone Number: +31887561101; Email: S.M.vanRossum-5@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3508GA
    • Recruiting
    • UMC Utrecht / Wilhelmina Children's Hospital
    • Contact: K van Loon, MD, PhD; Phone Number: +31 88 75 59475; Email: K.vanLoon-2@umcutrecht.nl
    • Contact: I Ceelie, MD, PhD; Phone Number: +31 88 75 59475; Email: I.Ceelie-2@umcutrecht.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients are term infants within 42 days (6 weeks) after birth, or infants prematurely born (with a gestational age >32 weeks) at a corrected age of <42 days, who are scheduled for cardiac or non-cardiac surgery.

Description

Inclusion Criteria:

• Term infant aged < 42 days / Preterm born > 32 weeks and with a corrected age < 42 days
• (Semi-) elective cardiac of major non-cardiac surgery
• Routine placement of an arterial cannula for invasive blood pressure monitoring.

Exclusion Criteria:

• Grade III-IV intracranial hemorrhage.
• Emergency surgery or semi-elective surgery performed out of hours.
• Informed consent from the parents is not obtained.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Critical Closing Pressure (CrCP)	Detection of the critical closing pressure (CrCP) of the brain, the arterial blood pressure at which brain vessels collapse and cerebral blood flow ceases, in a cohort of neonates who need major cardiac surgery. We hypothesize that neonates have a unique CrCP and cerebral ischemia occurs during episodes with critically endangered blood supply to the brain, when the arterial blood pressure (iABP) is below CrCP.	During congenital heart surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence white matter injury (WMI) on the postoperative MRI.	Compare CrCP between outcome groups, absent or new white matter injury (WMI) on the postoperative MRI.	Within the first postoperative 10 days

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: Kim van Loon, MD, PhD, University Medical Center Utrecht / Wilhelmina Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2022
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: TCD; hypoperfusion; critical closing pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: NL76532.041.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No